Publications by authors named "Michael Nolan"

169 Publications

Dual promotional effect of Cu O clusters grown with atomic layer deposition on TiO for photocatalytic hydrogen production.

Catal Sci Technol 2022 Jul 8;12(14):4511-4523. Epub 2022 Jun 8.

Department of Chemical Engineering, Delft University of Technology Van der Maasweg 9 2629 HZ Delft The Netherlands

The promotional effects on photocatalytic hydrogen production of Cu O clusters deposited using atomic layer deposition (ALD) on P25 TiO are presented. The structural and surface chemistry study of Cu O/TiO samples, along with first principles density functional theory simulations, reveal the strong interaction of ALD deposited Cu O with TiO, leading to the stabilization of Cu O clusters on the surface; it also demonstrated substantial reduction of Ti to Ti on the surface of Cu O/TiO samples after Cu O ALD. The Cu O/TiO photocatalysts showed remarkable improvement in hydrogen productivity, with 11 times greater hydrogen production for the optimum sample compared to unmodified P25. With the combination of the hydrogen production data and characterization of Cu O/TiO photocatalysts, we inferred that ALD deposited Cu O clusters have a dual promotional effect: increased charge carrier separation and improved light absorption, consistent with known copper promoted TiO photocatalysts and generation of a substantial amount of surface Ti which results in self-doping of TiO and improves its photo-activity for hydrogen production. The obtained data were also employed to modify the previously proposed expanding photocatalytic area and overlap model to describe the effect of cocatalyst size and weight loading on photocatalyst activity. Comparing the trend of surface Ti content increase and the photocatalytically promoted area, calculated with our model, suggests that the depletion zone formed around the heterojunction of Cu O-TiO is the main active area for hydrogen production, and the hydrogen productivity of the photocatalyst depends on the surface coverage by this active area. However, the overlap of these areas suppresses the activity of the photocatalyst.
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http://dx.doi.org/10.1039/d2cy00400cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291445PMC
July 2022

Large piezoelectric response in ferroelectric/multiferroelectric metal oxyhalide MOX (M = Ti, V and X = F, Cl and Br) monolayers.

Nanoscale 2022 Aug 1. Epub 2022 Aug 1.

Tyndall National Institute, Lee Maltings, Dyke Parade, University College Cork, T12R5CP Cork, Ireland.

Flexible two-dimensional (2D) piezoelectric materials are promising for applications in wearable electromechanical nano-devices such as sensors, energy harvesters, and actuators. A large piezo-response is required for any practical applications. Based on first-principles calculations, we report that ferroelectric TiOX and multiferroelectric VOX (X = F, Cl, and Br) monolayers exhibit large in-plane stress () and strain () piezoelectric coefficients. For example, the in-plane piezo-response of TiOBr (both = 28.793 × 10 C m and = 37.758 pm V) is about an order of magnitude larger than that of the widely studied 1H-MoS monolayer, and also quite comparable to the giant piezoelectricity of group-IV monochalcogenide monolayers, , SnS. Moreover, the of MOX monolayers - ranging from 29.028 pm V to 37.758 pm V - are significantly higher than the or of commonly used 3D piezoelectrics such as w-AlN ( = 5.1 pm V) and α-quartz ( = 2.3 pm V). Such a large of MOX monolayers originates from low in-plane elastic constants with large due to large Born effective charges () and atomic sensitivity to an applied strain. Moreover, we show the possibility of opening a new way of controlling piezoelectricity by applying a magnetic field.
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http://dx.doi.org/10.1039/d2nr02761eDOI Listing
August 2022

Stereotactic radiotherapy (10 Gy X 3) for canine nonlymphomatous intranasal tumors is associated with prolonged survival and minimal risk of severe radiotoxicity.

J Am Vet Med Assoc 2022 Jun 22:1-11. Epub 2022 Jun 22.

1Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

Objective: To describe oncologic outcomes following administration of a uniform stereotactic radiotherapy protocol (SRT; 10 Gy X 3) for canine intranasal tumors and to identify whether any clinical or dosimetric factors were predictive of event-free or overall survival time (EFST or OST).

Animals: 129 dogs.

Procedures: In this single-institution retrospective study, the medical records database was searched for canine nonlymphomatous intranasal tumors treated with 10 Gy X 3 SRT between August 2013 and November 2020. Findings regarding adverse effects and outcomes were analyzed overall, for dogs grouped on the basis of life stage (mature adult, senior, or end of life), and for treatment-related or tumor-related variables to identify potential predictors of outcome.

Results: After SRT, most dogs clinically improved with minimal acute radiotoxicity. The median EFST was 237 days; median OST was 542 days. Receipt of other tumor-directed therapies before or after SRT was associated with improved EFST in senior dogs (hazard ratio [HR], 0.416) and improved OST in mature adult (HR, 0.241) and senior dogs (HR, 0.348). In senior dogs, administration of higher near-minimum radiation doses was associated with improved EFST (HR, 0.686) and OST (HR, 0.743). In senior dogs, chondrosarcoma was associated with shorter OST (HR, 7.232), and in dogs at end of life, having a squamous cell or transitional carcinoma was associated with worse EFST (HR, 6.462).

Clinical Relevance: This SRT protocol results in improved quality of life and prolonged OST for dogs of all life stages. Radiation protocol optimization or use of multimodal therapy may further improve outcomes.
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http://dx.doi.org/10.2460/javma.22.03.0141DOI Listing
June 2022

Near-zero cohesion and loose packing of Bennu's near subsurface revealed by spacecraft contact.

Sci Adv 2022 Jul 7;8(27):eabm6229. Epub 2022 Jul 7.

Université Côte d'Azur, Observatoire de la Côte d'Azur, CNRS, Laboratoire Lagrange, Nice, France.

When the OSIRIS-REx spacecraft pressed its sample collection mechanism into the surface of Bennu, it provided a direct test of the poorly understood near-subsurface physical properties of rubble-pile asteroids, which consist of rock fragments at rest in microgravity. Here, we find that the forces measured by the spacecraft are best modeled as a granular bed with near-zero cohesion that is half as dense as the bulk asteroid. The low gravity of a small rubble-pile asteroid such as Bennu effectively weakens its near subsurface by not compressing the upper layers, thereby minimizing the influence of interparticle cohesion on surface geology. The underdensity and weak near subsurface should be global properties of Bennu and not localized to the contact point.
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http://dx.doi.org/10.1126/sciadv.abm6229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262326PMC
July 2022

Atomic Layer Deposition of Intermetallic FeZn Thin Films from Diethyl Zinc.

Chem Mater 2022 Jun 23;34(11):5241-5248. Epub 2022 May 23.

Department of Chemistry and Materials Science, Aalto University, FI-00076 Espoo, Finland.

We present a new type of atomic layer deposition (ALD) process for intermetallic thin films, where diethyl zinc (DEZ) serves as a coreactant. In our proof-of-concept study, FeCl is used as the second precursor. The FeCl + DEZ process yields in situ crystalline FeZn thin films, where the elemental purity and Fe/Zn ratio are confirmed by time-of-flight elastic recoil detection analysis (TOF-ERDA), Rutherford backscattering spectrometry (RBS), atomic absorption spectroscopy (AAS), and energy-dispersive X-ray spectroscopy (EDX) analyses. The film thickness is precisely controlled by the number of precursor supply cycles, as expected for an ALD process. The reaction mechanism is addressed by computational density functional theory (DFT) modeling. We moreover carry out preliminary tests with CuCl and Ni(thd) in combination with DEZ to confirm that these processes yield Cu-Zn and Ni-Zn thin films with DEZ as well. Thus, we envision an opening of a new ALD approach based on DEZ for intermetallic/metal alloy thin films.
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http://dx.doi.org/10.1021/acs.chemmater.2c00907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202305PMC
June 2022

Assessing the Sampleability of Bennu's Surface for the OSIRIS-REx Asteroid Sample Return Mission.

Space Sci Rev 2022 19;218(4):20. Epub 2022 Apr 19.

NASA Goddard Spaceflight Center, Greenbelt, MD USA.

NASA's first asteroid sample return mission, OSIRIS-REx, collected a sample from the surface of near-Earth asteroid Bennu in October 2020 and will deliver it to Earth in September 2023. Selecting a sample collection site on Bennu's surface was challenging due to the surprising lack of large ponded deposits of regolith particles exclusively fine enough ( diameter) to be ingested by the spacecraft's Touch-and-Go Sample Acquisition Mechanism (TAGSAM). Here we describe the Sampleability Map of Bennu, which was constructed to aid in the selection of candidate sampling sites and to estimate the probability of collecting sufficient sample. "Sampleability" is a numeric score that expresses the compatibility of a given area's surface properties with the sampling mechanism. The algorithm that determines sampleability is a best fit functional form to an extensive suite of laboratory testing outcomes tracking the TAGSAM performance as a function of four observable properties of the target asteroid. The algorithm and testing were designed to measure and subsequently predict TAGSAM collection amounts as a function of the minimum particle size, maximum particle size, particle size frequency distribution, and the tilt of the TAGSAM head off the surface. The sampleability algorithm operated at two general scales, consistent with the resolution and coverage of data collected during the mission. The first scale was global and evaluated nearly the full surface. Due to Bennu's unexpected boulder coverage and lack of ponded regolith deposits, the global sampleability efforts relied heavily on additional strategies to find and characterize regions of interest based on quantifying and avoiding areas heavily covered by material too large to be collected. The second scale was site-specific and used higher-resolution data to predict collected mass at a given contact location. The rigorous sampleability assessments gave the mission confidence to select the best possible sample collection site and directly enabled successful collection of hundreds of grams of material.
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http://dx.doi.org/10.1007/s11214-022-00887-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018658PMC
April 2022

An approach to determining, delivering, and assessing essential course content in a medical human anatomy course.

Clin Anat 2022 Sep 14;35(6):789-794. Epub 2022 May 14.

Department of Basic Science Education, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA.

Learning objectives typically indicate subject matter judged to be important or that represents essential material to be learned during a course. We report here on our efforts to identify essential course content and determine our effectiveness teaching and assessing this content in our preclinical human anatomy course. Using a consensus driven approach, we identified anatomical structures, relationships, and functional concepts judged to represent essential material in our unit on the thorax that students were expected to be familiar with. We then determined performance on specific examination questions that focused directly on the essential material. Thirty-seven of 48 students (77%) correctly answered all 34 of 51 questions that directly focused on content we defined as essential. The remaining 11 students answered the majority of these questions correctly. The overall mean score was 86% (range 61%-98%). Our review of student performance on the End of Block thorax examination confirmed our belief that we were successful in helping students learn material we defined as essential. We found the process described here to be helpful in defining essential content and for helping focus and improve medical education and learning assessment based on that material. We believe the idea of defining essential content that can be efficiently taught and effectively learned within a proscribed period of time is an important and necessary objective. We believe the approach used here might be successfully utilized in other programs in efforts aimed at quality improvement.
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http://dx.doi.org/10.1002/ca.23911DOI Listing
September 2022

A retrospective study of 101 dogs with oral melanoma treated with a weekly or biweekly 6 Gy × 6 radiotherapy protocol.

Vet Comp Oncol 2022 Sep 3;20(3):623-631. Epub 2022 Apr 3.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.

One radiotherapy (RT) protocol used for canine oral melanoma (OM) gives 36 Gy total, in six weekly or biweekly fractions (6 Gy × 6). This retrospective study characterizes oncologic outcomes for a relatively large group of dogs treated with this protocol and determines whether radiation dose intensity (weekly vs. biweekly) affected either progression-free or overall survival (PFS and OS). Dogs were included if 6 Gy × 6 was used to treat grossly evident OM, or if RT was used postoperatively in the subclinical disease setting. Kaplan-Meier statistics and Cox regression modelling were used to determine the predictive or prognostic value of mitotic count, bony lysis, World Health Organization (WHO) stage (I, II, III, or IV), using systemic anti-cancer therapies, tumour burden at the time of RT (macroscopic vs. subclinical), radiation dose intensity (weekly vs. biweekly), and treatment planning type (manual vs. computerized). The median PFS and OS times for all dogs (n = 101) were 171 and 232 days, respectively. On univariate analysis PFS and OS were significantly longer (p = <.05) with subclinical tumour burden, WHO stages I or II, and weekly irradiation. On multivariable analysis, only tumour stage remained significant; therefore, cases were grouped by WHO stage (I/II vs. III/IV). With low WHO stage (I/II), PFS and OS were longer when irradiating subclinical disease (PFS: risk ratio = 0.449, p = .032; OS: risk ratio = 0.422, p = .022); this was not true for high WHO stage (III/IV). When accounting for other factors, radiation dose intensity had no measurable impact on survival in either staging group.
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http://dx.doi.org/10.1111/vco.12815DOI Listing
September 2022

Atomic/molecular layer deposition of cerium(III) hybrid thin films using rigid organic precursors.

Dalton Trans 2022 Apr 5;51(14):5603-5611. Epub 2022 Apr 5.

Inorganic Materials Chemistry, Ruhr University Bochum, Universitätsstraße 150, 44801 Bochum, Germany.

An atomic/molecular layer deposition (ALD/MLD) process for the fabrication of cerium-based metal-organic hybrid films is demonstrated for the first time. The highly reactive cerium(III) guanidinate precursor [Ce(dpdmg)] was employed in combination with organic precursors composed of rigid backbones, terephthalic acid (TPA) and hydroquinone (HQ) for the growth of the respective hybrid films. Growth rates of the films as high as 5.4 Å per cycle for Ce-TPA and 4.8 Å per cycle for Ce-HQ at a deposition temperature of 200 °C were obtained. Density functional theory (DFT) investigations confirm the favorable interaction between the cerium precursor and the organic co-reactants and predict that Ce maintains its +3 oxidation state in the films. This was also confirmed experimentally by X-ray photoelectron spectroscopy (XPS). Additionally, the films are highly UV absorbing. Hence, we envision that these films could find future application as promising redox active materials and/or UV absorbing materials.
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http://dx.doi.org/10.1039/d2dt00353hDOI Listing
April 2022

Self-limiting nitrogen/hydrogen plasma radical chemistry in plasma-enhanced atomic layer deposition of cobalt.

Nanoscale 2022 Mar 24;14(12):4712-4725. Epub 2022 Mar 24.

Tyndall National Institute, University College Cork, Lee Maltings, Dyke Parade, Cork, T12 R5CP, Ireland.

Cobalt (Co) is a potential candidate in replacing copper for interconnects and has been applied in trenches in the semiconductor industry for over twenty years. A non-oxidizing reactant is required in the plasma-enhanced atomic layer deposition (PE-ALD) of thin films of metals to avoid O-contamination. PE-ALD of Co has been demonstrated experimentally with plasma sources of NH or a mixture of N and H, but the growth mechanism and key reactions are not clear. In this study, we have investigated the reactions of plasma-generated predominant species, radicals ˙H, ˙N, ˙NH and ˙NH, at metal precursor (CoCp) treated Co(001) and Co(100) surfaces using static DFT calculations at 0 K and molecular dynamics simulations at 600 K. The proposed reaction mechanisms are (1) ˙N radicals play an important role in eliminating the surface-bound Cp ligand (if any) pyridine (CHN) formation and desorption, whereas ˙H radicals have endothermic reactions for eliminating the Cp ligand CpH formation and desorption; (2) the surface NH species are eliminated by ˙H radicals NH formation and desorption. The simulations of these key reactions show that on the Co(001) surface, the remaining Cp ligand and surface NH species after the metal precursor pulse will be completely removed with ˙N and ˙H radicals, resulting in Co atoms deposited on the Co(001) surface at a coverage of 3.03 Co nm. However, on the Co(100) surface, the surface NH species cannot be completely removed NH formation and desorption due to overall endothermic reactions. Instead, ˙H radicals react with trench N species, resulting from H transfer in the metal precursor pulse, to form NH. These trench N species cannot be eliminated completely on the Co(100) surface, which will be the source of N impurities in the deposited Co thin films. At the post-plasma stage, the metal surface will be covered with NH-terminations with plasma generated ˙NH radicals and is then ready for the next deposition cycle. Our DFT results highlight and explain why ammonia or H/N plasma, which produce NH species, are required to deposit high-quality and low-impurity Co thin films using Co metallocene precursors.
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http://dx.doi.org/10.1039/d1nr05568bDOI Listing
March 2022

Intensity of perioperative analgesia but not pre-treatment pain is predictive of survival in dogs undergoing amputation plus chemotherapy for extremity osteosarcoma.

Vet Comp Oncol 2022 Sep 21;20(3):568-576. Epub 2022 Mar 21.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.

The purpose of this bi-institutional retrospective study was to determine whether, in dogs treated with limb amputation and adjunctive chemotherapy for osteosarcoma, oncologic outcomes are impacted by either: (1) baseline cancer pain severity, or (2) the approaches used for perioperative pain management. Data were extracted from the medical records of 284 dogs that underwent both limb amputation and chemotherapy (carboplatin and/or doxorubicin) between 1997 and 2017 for localized (non-metastatic) osteosarcoma of the appendicular skeleton. Kaplan-Meier survival curves and Cox proportional hazard (PH) models were used to determine the impact that retrospectively scored baseline pain levels (high vs. low) and various analgesic and local anaesthetic treatments had on both metastasis-free survival and all-cause mortality. For the entire population, the median disease free interval and median overall survival times were 253 and 284 days, respectively. Baseline pain was rated as "low" in 84 dogs, and "high" in 190 dogs; pain severity had no detectable effect on either metastasis-free survival or all-cause mortality. When accounting for the potential influences of known prognostic factors, dogs treated with what was characterized as a high-intensity perioperative analgesic plan (including both a non-steroidal anti-inflammatory drug [NSAID] and a bupivacaine-eluting soaker catheter placed at the amputation site) had a higher probability of survival than dogs treated with a low-intensity perioperative analgesic plan (neither an NSAID, nor a soaker catheter); the median overall survival times were 252 and 378 days, respectively (hazard ratio: 2.922; p = .020).
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http://dx.doi.org/10.1111/vco.12808DOI Listing
September 2022

Negative Piezoelectric Coefficient in Ferromagnetic 1H-LaBr Monolayer.

ACS Appl Electron Mater 2022 Feb 15;4(2):850-855. Epub 2022 Jan 15.

Tyndall National Institute, University College Cork, Lee Maltings, Dyke Parade, T12 R5CP Cork, Ireland.

The discovery of two-dimensional (2D) magnetic materials that have excellent piezoelectric response is promising for nanoscale multifunctional piezoelectric or spintronic devices. Piezoelectricity requires a noncentrosymmetric structure with an electronic band gap, whereas magnetism demands broken time-reversal symmetry. Most of the well-known 2D piezoelectrics, e.g., 1H-MoS monolayer, are not magnetic. Being intrinsically magnetic, semiconducting 1H-LaBr and 1H-VS monolayers can combine magnetism and piezoelectricity. We compare piezoelectric properties of 1H-MoS, 1H-VS, and 1H-LaBr using density functional theory. The ferromagnetic 1H-LaBr and 1H-VS monolayers display larger piezoelectric strain coefficients, namely, = -4.527 pm/V for 1H-LaBr and = 4.104 pm/V for 1H-VS, compared to 1H-MoS ( = 3.706 pm/V). 1H-MoS has a larger piezoelectric stress coefficient ( = 370.675 pC/m) than 1H-LaBr ( = -94.175 pC/m) and 1H-VS ( = 298.100 pC/m). The large for 1H-LaBr originates from the low elastic constants, = 30.338 N/m and = 9.534 N/m. The sign of the piezoelectric coefficients for 1H-LaBr is negative, and this arises from the negative ionic contribution of , which dominates in 1H-LaBr, whereas the electronic part of dominates in 1H-MoS and 1H-VS. We explain the origin of this large ionic contribution of for 1H-LaBr through Born effective charges ( ) and the sensitivity of the atomic positions to the strain (d/dη). We observe a sign reversal in the values of Mo and S compared to the nominal oxidation states, which makes both the electronic and ionic parts of positive and results in the high value of . We also show that a change in magnetic order can enhance (reduce) the piezoresponse of 1H-LaBr (1H-VS).
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http://dx.doi.org/10.1021/acsaelm.1c01214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8867721PMC
February 2022

Control of the Cu morphology on Ru-passivated and Ru-doped TaN surfaces - promoting growth of 2D conducting copper for CMOS interconnects.

Chem Sci 2022 Jan 13;13(3):713-725. Epub 2021 Dec 13.

Tyndall National Institute, University College Cork Lee Maltings, Dyke Parade Cork T12 R5CP Ireland

Prolonging the lifetime of Cu as a level 1 and level 2 interconnect metal in future nanoelectronic devices is a significant challenge as device dimensions continue to shrink and device structures become more complex. At nanoscale dimensions Cu exhibits high resistivity which prevents its functioning as a conducting wire and prefers to form non-conducting 3D islands. Given that changing from Cu to an alternative metal is challenging, we are investigating new materials that combine properties of diffusion barriers and seed liners to reduce the thickness of this layer and to promote successful electroplating of Cu to facilitate the coating of high-aspect ratio interconnect vias and to allow for optimal electrical conductance. In this study we propose new combined barrier/liner materials based on modifying the surface layer of the TaN barrier through Ru incorporation. Simulating a model Cu structure at 0 K and through finite temperature molecular dynamics on these surfaces allows us to demonstrate how the Ru content can control copper wetting, adhesion and thermal stability properties. Activation energies for atom migrations onto a nucleating copper island allow insight into the growth mechanism of a Cu thin-film. Using this understanding allows us to tailor the Ru content on TaN to control the final morphology of the Cu film. These Ru-modified TaN films can be deposited by atomic layer deposition, allowing for fine control over the film thickness and composition.
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http://dx.doi.org/10.1039/d1sc04708fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768880PMC
January 2022

Small group learning/assessment sessions: A method using test enhanced learning to increase engagement in a basic medical science neuroanatomy course.

Clin Anat 2022 Apr 4;35(3):359-365. Epub 2022 Feb 4.

Department of Basic Science Education, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA.

Previous research has shown that test-enhanced learning with structured feedback facilitates durable learning. We describe a small group learning/assessment activity using these approaches intended to increase engagement and engagement with the course material. We divided our class into six groups of seven students each that worked together in the activity. During each weekly session, course related multiple choice questions were projected and each group instructed to work independently to arrive at a consensus answer for each question. After each question is considered, a faculty facilitator then randomly selects one group to share their choice with the other groups and provide and rationale for their choice. A different group or groups are then called upon to share their choice. When differences emerge, the instructor then facilitates discussion among the groups in an effort to resolve confusion or incomplete or incorrect understanding that becomes evident. We found that attendance for these sessions was greater than for the more traditional lecture based session also included in the course and that students were actively engaged in this learning activity. The success of the small group learning/assessment session is dependent on several factors including the difficulty of the questions and their relatedness to the course objectives, the timing and placement of the session or sessions within the course and the skill of the faculty facilitator in encouraging active participation while ensuring a safe environment in which students can openly share their sometimes incomplete or incorrect understanding of the material.
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http://dx.doi.org/10.1002/ca.23839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303715PMC
April 2022

Re-irradiation of canine non-lymphomatous nasal tumours using stereotactic radiation therapy (10 Gy x 3) for both courses: Assessment of outcome and toxicity in 11 dogs.

Vet Comp Oncol 2022 Jun 13;20(2):502-508. Epub 2022 Feb 13.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.

No uniformly beneficial treatments exist for dogs with non-lymphomatous nasal tumours (NLNT) that relapse after radiotherapy (RT). Reirradiation may prolong survival and improve quality of life. In this retrospective study, we describe outcomes for 11 dogs that had CT-confirmed locoregional progression of NLNT after an initial course of stereotactic RT (SRT#1; 10 Gy × 3) and were then re-treated with the same type of protocol (SRT#2, also 10 Gy × 3). The median time between SRT #1 and SRT #2 was 243 days (95% CI: 78-385 days). Ten dogs (91%) had a clinical benefit after SRT#1; five dogs (45%) had clinical benefit after SRT#2. Adverse events after SRT#2 included nasocutaneous or oronasal fistula formation (N = 3 at 180, 270, and 468 days), seizures (N = 2 at 78 and 330 days), bacterial or fungal rhinitis (N = 2 at 240 and 385 days), and facial swelling (N = 1 at 90 days). All 11 dogs have died, due to disease progression, presumed radiotoxicity, or declining quality of life; in most cases, it was difficult to discern between these conditions. The median overall survival time (OST) from SRT#1 was 745 days (95% CI: 360-1132). The median overall survival time (OST) from SRT #2 was 448 days (95% CI: 112-626). For these dogs, survival was prolonged, but adverse events after SRT#2 were common (8/11; 73%). Therefore, before consenting to re-irradiation with this protocol, pet owners should be counselled about survivorship challenges, including risk for severe toxicities, and persistence of clinical signs.
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http://dx.doi.org/10.1111/vco.12801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305852PMC
June 2022

Anatomy of the physical examination: A small group learning approach for increasing engagement and learning in a medical gross anatomy course.

Clin Anat 2022 Mar 31;35(2):256-262. Epub 2021 Dec 31.

Department of Basic Science Education, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA.

The ability to perform and interpret the physical examination requires an understanding of human anatomy and how to apply that content in the clinical setting. Previous work has shown that students understand and retain information more effectively when they are actively engaged in the learning process and it is clearly linked to other coursework and their future needs. We developed a series of learning activities, based on the general physical examination, designed to enhance engagement and encourage durable learning of anatomical principles that are important in performing and interpreting the physical examination. Activities were designed for use in small group settings with faculty supervision and input as needed. We describe these activities and provide comments from students regarding the perceived value of these learning activities. Students reported that the applied anatomy learning activities were engaging and aided in their learning of human anatomy. Additionally, students appreciated the connection between the applied anatomy activities and the skills being learned in concurrent coursework focusing on the physical examination. We observed that applied human anatomy exercises modeled after components of the general physical examination and embedded in an anatomy course enhanced student engagement and helped students appreciate the importance of anatomical principles. We note that sensitivity to and acceptance of personal preferences and religious matters must be shown when using learning activities that involve close physical interactions to teach anatomical topics.
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http://dx.doi.org/10.1002/ca.23829DOI Listing
March 2022

Role of terminal groups in aromatic molecules on the growth of AlO-based hybrid materials.

Dalton Trans 2021 Dec 7;50(47):17583-17593. Epub 2021 Dec 7.

Tyndall National Institute, Lee Maltings Complex Dyke Parade, Cork, Cork, T12 R5CP, Ireland.

Hybrid materials composed of organic and inorganic components offer the opportunity to develop interesting materials with well-controlled properties. Molecular Layer Deposition (MLD) is a suitable thin film deposition technique for the controlled growth of thin, conformal hybrid films. Despite the great interest in these materials, a detailed understanding of the atomistic mechanism of MLD film growth is still lacking. This paper presents a first principles investigation of the detailed mechanism of the growth of hybrid organic-inorganic thin films of aluminium oxide and aromatic molecules with different terminal groups deposited by MLD. We investigate the chemistry of the MLD process between the post-TMA pulse methyl-terminated AlO surface and the homo- or hetero-bifunctional aromatic compounds with hydroxy (OH) and/or amino (NH) terminal groups: hydroquinone (HQ), -phenylenediamine (PD) and 4-aminophenol (AP). Double reactions of aromatic molecules with the alumina surface are also explored. We show that all aromatic precursor molecules bind favourably to the methyl terminated AlO, formation of Al-O and Al-N bonds and CH elimination. While reaction energetics suggest a higher reactivity of the OH group with TMA in comparison to the NH group, which could enable the double reaction phenomenon for HQ, we propose that the upright configuration will be present so that the organic molecules are self-assembled in an upright configuration, which leads to thicker hybrid films. Interactions between the methyl-terminated AlO with substituted phenyls are investigated to examine the influence of phenyl functionalisation on the chemistry of the terminal groups. Reaction energetics show that phenyl functionalization actually promotes an upright configuration of the molecule, which leads to thicker and more flexible films, as well as tuning the properties of the aromatic components of the hybrid films. We also investigate the interactions between methyl-terminated AlO with new possible MLD organic precursors, hydroquinone bis(2-hydroxyethyl)ether and 1,1'-biphenyl-4,4'-diamine. DFT shows that both aromatic molecules react favourably with TMA and are worthy of further experimental investigation.
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http://dx.doi.org/10.1039/d1dt03195cDOI Listing
December 2021

Endocrine response and outcome in 14 cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (17 Gy).

Am J Vet Res 2021 Nov 12;83(1):64-71. Epub 2021 Nov 12.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

Objective: To describe clinical outcomes in cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (SRS).

Animals: 14 client-owned cats.

Procedures: Medical records of cats with insulin resistance and acromegaly treated with SRS (17 Gy) between August 2013 and November 2019 at a single institution were reviewed. Kaplan-Meier analysis was used to evaluate overall survival time.

Results: Acute adverse effects of SRS included somnolence (n = 2) and alopecia (1). Delayed adverse effects of SRS included unspecified neurologic complications (n = 1; 481 days), seizures (1; 1,541 days), and hypothyroidism (1; 64 days). Exogenous insulin requirements decreased in 10 of the 14 cats, with a median time to lowest insulin dose of 399 days (range, 42 to 879 days). Complete diabetic remission was achieved in 3 cats. The median overall survival time was 741 days (95% CI, 353 to 1,129 days). Six cats were still alive at the end of the study period, with a median follow-up time of 725 days. In 7 of the 8 cats that had died, death was presumptively attributed to acromegaly owing to continued insulin resistance, organ failure, or altered neurologic status.

Clinical Relevance: The SRS protocol was well tolerated and associated with survival times similar to those reported previously. Most cats had decreased exogenous insulin requirements after SRS. Latency to an endocrine response was highly variable, emphasizing the need for careful ongoing diabetic monitoring of acromegalic cats after pituitary gland irradiation.
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http://dx.doi.org/10.2460/ajvr.21.08.0122DOI Listing
November 2021

Relevance of assessment items in community paramedicine home visit programmes: results of a modified Delphi study.

BMJ Open 2021 11 11;11(11):e048504. Epub 2021 Nov 11.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.

Objective: Guidelines for a structured assessment in community paramedicine home visit programmes have not been established and evidence to inform their creation is lacking. We sought to investigate the relevance of assessment items to the practice of community paramedics according to a pre-established clarity-utility matrix.

Design: We designed a modified-Delphi study consisting of predetermined thresholds for achieving consensus, number of rounds of for scoring items, a defined meeting and discussion process, and a sample of participants that was purposefully representative.

Setting And Participants: We established a panel of 26 community paramedics representing 20 municipal paramedic services in Ontario, Canada. The sample represented a majority of paramedic services within the province that were operating a community paramedicine home visit programme.

Measures: Drawing from a bank of standardised assessment items grouped according to domains aligned with the International Classification on Functioning, Disability, and Health taxonomy, 64 previously pilot-tested assessment items were scored according to their clarity (being free from ambiguity and easy to understand) and utility (being valued in care planning or case management activities). Assessment items covered a broad range of health, social and environmental domains. To conclude scoring rounds, assessment items that did not achieve consensus for relevance to assessment practices were discussed among participants with opportunities to modify assessment items for subsequent rounds of scoring.

Results: Resulting from the first round of scoring, 54 assessment items were identified as being relevant to assessment practices and 3 assessment items were removed from subsequent rounds. The remaining 7 assessment items were modified, with some parts removed from the final items that achieved consensus in the final rounds of scoring.

Conclusion: A broadly representative panel of community paramedics identified consensus for 61 assessment items that could be included in a structured, multidomain, assessment instrument for guiding practice in community paramedicine home visit programmes.

Trail Registration Number: ISRCTN58273216.
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http://dx.doi.org/10.1136/bmjopen-2020-048504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587454PMC
November 2021

Transcriptomic effects of rs4845604, an IBD and allergy-associated RORC variant, in stimulated ex vivo CD4+ T cells.

PLoS One 2021 21;16(10):e0258316. Epub 2021 Oct 21.

Human Genetics, GlaxoSmithKline Medicine Research Centre, Stevenage, England.

RORγt is an isoform of RORC, preferentially expressed in Th17 cells, that functions as a critical regulator of type 3 immunity. As murine Th17-driven inflammatory disease models were greatly diminished in RORC knock-out mice, this receptor was prioritised as an attractive therapeutic target for the treatment of several autoimmune diseases. Human genetic studies indicate a significant contributory role for RORC in several human disease conditions. Furthermore, genome-wide association studies (GWAS) report a significant association between inflammatory bowel disease (IBD) and the RORC regulatory variant rs4845604. To investigate if the rs4845604 variant may affect CD4+ T cell differentiation events, naïve CD4+ T cells were isolated from eighteen healthy subjects homozygous for the rs4845604 minor (A) or major (G) allele). Isolated cells from each subject were differentiated into distinct T cell lineages by culturing in either T cell maintenance medium or Th17 driving medium conditions for six days in the presence of an RORC inverse agonist (to prevent constitutive receptor activity) or an inactive diastereomer (control). Our proof of concept study indicated that genotype had no significant effect on the mean number of naïve CD4 T cells isolated, nor the frequency of Th1-like and Th17-like cells following six days of culture in any of the four culture conditions. Analysis of the derived RNA-seq count data identified genotype-driven transcriptional effects in each of the four culture conditions. Subsequent pathway enrichment analysis of these profiles reported perturbation of metabolic signalling networks, with the potential to affect the cellular detoxification response. This investigation reveals that rs4845604 genotype is associated with transcriptional effects in CD4+ T cells that may perturb immune and metabolic pathways. Most significantly, the rs4845604 GG, IBD risk associated, genotype may be associated with a differential detoxification response. This observation justifies further investigation in a larger cohort of both healthy and IBD-affected individuals.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258316PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530322PMC
November 2021

A study on the influence of ligand variation on formamidinate complexes of yttrium: new precursors for atomic layer deposition of yttrium oxide.

Dalton Trans 2021 Sep 28;50(37):12944-12956. Epub 2021 Sep 28.

Inorganic Materials Chemistry, Ruhr University Bochum, Universitätsstr. 150, 44801 Bochum, Germany.

The synthesis and characterization of a series of closely related Y(III) compounds comprising the formamidinate ligands (RNCHNR) (R = alkyl) is reported, with the scope of using them as prospective precursors for atomic layer deposition (ALD) of yttrium oxide (YO) thin films. The influence of the side chain variation on the thermal properties of the resulting complexes is studied and benchmarked by thermal analysis and vapor pressure measurements. Density functional theory (DFT) studies give theoretical insights into the reactivity of the compounds towards water, which was targeted as a co-reactant for the deposition of YO thermal ALD in the next step. Among the four complexes analyzed, tris(,'-di--butyl-formamidinato)yttrium(III) [Y(Bu-famd)] 1 was found to possess enhanced thermal stability and was selected for YO ALD process development. A broad ALD window ranging from 200 °C to 325 °C was obtained, yielding films of high compositional quality. Furthermore, with a film density of (4.95 ± 0.05) g cm close to the bulk value, polycrystalline YO layers with a smooth topography resulted in promising dielectric properties when implemented in metal insulator semiconductor (MIS) capacitor structures.
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http://dx.doi.org/10.1039/d1dt01634bDOI Listing
September 2021

Behavioral phenotyping of cancer pain in domesticated cats with naturally occurring squamous cell carcinoma of the tongue: initial validation studies provide evidence for regional and widespread algoplasticity.

PeerJ 2021 16;9:e11984. Epub 2021 Aug 16.

Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States of America.

Feline oral squamous cell carcinoma (FOSCC) is a common and naturally occurring condition that recapitulates many features of human head and neck cancer (HNC). In both species, there is need for improved strategies to reduce pain caused by HNC and its treatment. Research to benefit both species could be conducted using pet cats as a comparative model, but this prospect is limited by lack of validated methods for quantifying FOSCC-associated pain. A prospective non-randomized pilot study was performed for initial validation of: (1) a pet owner administered quality of life questionnaire and visual assessment scoring tool (FORQ/CLIENT); (2) a clinician assessment questionnaire (UFEPS/VET); (3) electronic von Frey testing [EVF]; and (4) Cochet-Bonnet (COBO) aesthesiometry. To assess intra-rater reliability, discriminatory ability, and responsiveness of each assay, 6 cats with sublingual SCC and 16 healthy control cats were enrolled. The intra-rater reliability was moderate-to-good for the clinical metrology instruments and EVF (intraclass correlation coefficient [ICC] ≥ 0.68), but poor for COBO (ICC = 0.21). FORQ/CLIENT scores were higher (worse quality of life) in FOSCC cats vs healthy controls. The internal reliability of FORQ/CLIENT scoring was high (Cronbach  = 0.92); sensitivity and specificity were excellent (100% when using cut-offs determined using receiver operating characteristic [ROC] curves). For the FORQ/CLIENT, there was strong and inverse correlation between scores from the questions and visual assessment ( =  - 0.77,  = 0.6, < 0.0001). For the UFEPS/VET, Cronbach's was 0.74 (high reliability). Sensitivity and specificity were 100% and 94%, respectively, when using a cut-off score (3.5) based on ROC curves (Youden index of 0.94). Total UFEPS/VET scores were positively correlated with FORQ/CLIENT scores (  = 0.72, < 0.0001). Sensitivity of EVF and COBO ranged from 83 to 100% and specificity ranged from 56 to 94%. Cats with cancer were more sensitive around the face (lower response thresholds) and on the cornea (longer filament lengths) than control animals ( < 0.03). Reduced pressure response thresholds were also observed at a distant site ( = 0.0002) in cancer cats. After giving buprenorphine, EVF pressure response thresholds increased ( = 0.04) near the mandible of cats with OSCC; the length of filament required to elicit a response in the COBO assay also improved (shortened; = 0.017). Based on these preliminary assessments, the assays described herein had reasonable inter-rater reliability, and they were able to both discriminate between cats with and without oral cancer, and respond in a predictable manner to analgesic therapy. In cats with tongue cancer, there was evidence for regional peripheral sensitization, and widespread somatosensory sensitization. These results provide a basis for multi-dimensional assessments of pain and sensitivity in cats with oral SCC.
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http://dx.doi.org/10.7717/peerj.11984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375511PMC
August 2021

Paramedics assessing patients with complex comorbidities in community settings: results from the CARPE study.

CJEM 2021 11 17;23(6):828-836. Epub 2021 Aug 17.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.

Objectives: The aim for this study was to provide information about how community paramedicine home visit programs best "navigate" their role delivering preventative care to frequent 9-1-1 users by describing demographic and clinical characteristics of their patients and comparing them to existing community care populations.

Methods: Our study used secondary data from standardized assessment instruments used in the delivery of home care, community support services, and community paramedicine home visit programs in Ontario. Identical assessment items from each instrument enabled comparisons of demographic, clinical, and social characteristics of community-dwelling older adults using descriptive statistics and z-tests.

Results: Data were analyzed for 29,938 home care clients, 13,782 community support services clients, and 136 community paramedicine patients. Differences were observed in proportions of individuals living alone between community paramedicine patients versus home care clients and community support clients (47.8%, 33.8%, and 59.9% respectively). We found higher proportions of community paramedicine patients with multiple chronic disease (87%, compared to 63% and 42%) and mental health-related conditions (43.4%, compared to 26.2% and 18.8% for depression, as an example).

Conclusion: When using existing community care populations as a reference group, it appears that patients seen in community paramedicine home visit programs are a distinct sub-group of the community-dwelling older adult population with more complex comorbidities, possibly exacerbated by mental illness and social isolation from living alone. Community paramedicine programs may serve as a sentinel support opportunity for patients whose health conditions are not being addressed through timely access to other existing care providers.

Protocol Registration: ISRCTN 58273216.
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http://dx.doi.org/10.1007/s43678-021-00153-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575756PMC
November 2021

Prediction of Co and Ru nanocluster morphology on 2D MoS from interaction energies.

Beilstein J Nanotechnol 2021 14;12:704-724. Epub 2021 Jul 14.

Tyndall National Institute, University College Cork, Lee Maltings, Dyke Parade, Cork, T12 R5CP, Ireland.

Layered materials, such as MoS, have a wide range of potential applications due to the properties of a single layer, which often differ from the bulk material. They are of particular interest as ultrathin diffusion barriers in semiconductor device interconnects and as supports for low-dimensional metal catalysts. Understanding the interaction between metals and the MoS monolayer is of great importance when selecting systems for specific applications. In previous studies the focus has been largely on the strength of the interaction between a single atom or a nanoparticle of a range of metals, which has created a significant knowledge gap in understanding thin film nucleation on 2D materials. In this paper, we present a density functional theory (DFT) study of the adsorption of small Co and Ru structures, with up to four atoms, on a monolayer of MoS. We explore how the metal-substrate and metal-metal interactions contribute to the stability of metal clusters on MoS, and how these interactions change in the presence of a sulfur vacancy, to develop insight to allow for a prediction of thin film morphology. The strength of interaction between the metals and MoS is in the order Co Ru. The competition between metal-substrate and metal-metal interaction allows us to conclude that 2D structures should be preferred for Co on MoS, while Ru prefers 3D structures on MoS. However, the presence of a sulfur vacancy decreases the metal-metal interaction, indicating that with controlled surface modification 2D Ru structures could be achieved. Based on this understanding, we propose Co on MoS as a suitable candidate for advanced interconnects, while Ru on MoS is more suited to catalysis applications.
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http://dx.doi.org/10.3762/bjnano.12.56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290098PMC
July 2021

Irradiation of the Normal Murine Tongue Causes Upregulation and Activation of Transient Receptor Potential (TRP) Ion Channels.

Radiat Res 2021 10;196(4):331-344

Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina.

Signal transduction at sensory neurons occurs via transmembrane flux of cations, which is largely governed by the transient receptor potential (TRP) family of ion channels. It is unknown whether TRP channel activation contributes to the pain that accompanies radiation-induced oral mucositis. This study sought to characterize changes in TRP channel expression and function that occur in the locally irradiated tissues and afferent neurons of mice. Female CD-1 mice received single high-dose (27 Gy) tongue irradiation, or sham irradiation. Animals were euthanized either before overt glossitis developed (days 1 and 5 postirradiation), when glossitis was severe (day 11), or after mice had recovered (days 21 and 45). Tongue irradiation caused upregulation of the Trpv1 gene in trigeminal ganglia (TG) neurons. Other TRP genes (Trpv2, Trpv4, Trpa1, Trpm8) and Gfrα3 (which acts upstream of several TRP channels) were also upregulated in TGs and/or tongue tissue, in response to radiation. Ex vivo calcium imaging experiments demonstrated that the proportions of TG neurons responding to histamine (an activator of TRPV1, TRPV4 and TRPA1), TNF-α (an activator of TRPV1, TRPV2 and TRPV4), and capsaicin (a TRPV1 agonist), were increased as early as one day after tongue irradiation; these changes persisted for at least 21 days. In a subsequent experiment, we found that genetic deletion of TRPV1 mitigated weight loss (a surrogate marker of pain severity) in mice with severe glossitis. The results intimate that various TRP channels, and TRPV1 in particular, should be explored as analgesic targets for patients experiencing pain after oral irradiation.
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http://dx.doi.org/10.1667/RADE-21-000103.1DOI Listing
October 2021

Unexpected but transient tumour enlargement preceded complete regression and long-term control after irradiation of squamous cell carcinoma in a red-eared slider ().

Vet Rec Case Rep 2020 Jun 16;8(2). Epub 2020 Apr 16.

Department of Clinical Sciences, North Carolina State University, USA.

A red-eared slider with a chronic non-healing ulcerative shell lesion was diagnosed with cutaneous squamous cell carcinoma (SCC). The animal underwent surgical debulking, and adjuvant hypofractionated radiation therapy. The lesion initially responded, with near complete tumour regression, but then began growing again just a few months after finishing radiotherapy. Then, after several months with no additional tumour-directed therapy, the lesion again regressed. Five years post-irradiation and with no further treatment, the turtle now remains tumour-free. This unusual pattern of disease regression followed by transient growth and then long-term local tumour control suggests either spontaneous remission, or a pseudoprogression-like phenomenon. Careful clinical follow-up and reporting of future cases will aid in determining whether this pseudoprogression-like event was random, versus being a common component of the chelonian response to irradiation of cutaneous SCC.
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http://dx.doi.org/10.1136/vetreccr-2019-001039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128154PMC
June 2020

Income Status and Life Satisfaction.

J Happiness Stud 2022 11;23(1):233-256. Epub 2021 May 11.

University of Hull, Cottingham Road, Hull, HU6 7RX UK.

The importance of both income rank and relative income, as indicators of status, has long been recognised in the literature on life satisfaction and happiness. Recently, several authors have made explicit comparisons of the relative importance of these two measures of income status, and concluded that rank dominates to the extent that reference income becomes insignificant in regressions including both these explanatory variables, and that even absolute or household income, otherwise always positively related to happiness, may lose statistical significance. Here we test this hypothesis with a large UK panel (British Household Panel Survey and Understanding Society) for 1996-2017, split by age and retirement status, and find, contrary to previous results, that rank, household income and reference income are all usually important explanatory variables, but with significant differences between subgroups. This finding holds when rank is in its often-used relative form, and also with absolute rank.
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http://dx.doi.org/10.1007/s10902-021-00397-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110693PMC
May 2021

Retrospective evaluation of intranasal carcinomas in cats treated with external-beam radiotherapy: 42 cases.

J Vet Intern Med 2021 Mar 3;35(2):1018-1030. Epub 2021 Mar 3.

College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.

Background: Little is known regarding the comparative efficacy of various irradiation strategies used to treat intranasal carcinomas (INC) in cats.

Objectives: Investigate outcomes and prognostic factors associated with survival for cats with INC.

Animals: Forty-two cats with INC that underwent radiotherapy (RT).

Methods: Single-arm retrospective study. Medical record review for cats with INC that underwent RT at 1 of 7 veterinary RT facilities. Irradiation protocols categorized as: definitive-intent fractionated RT (FRT), definitive-intent stereotactic RT (SRT), and palliative-intent RT (PRT). Median overall survival time (OST) and disease progression-free survival (PFS; documented by advanced transverse imaging, or recurrence of symptoms) were calculated. Associations between tumor stage, RT protocol/intent, and adjunctive treatment usage and outcome were calculated.

Results: Cats underwent SRT (N = 18), FRT (N = 8), and PRT (N = 16). In multivariate modeling, cats received definitive-intent treatment (DRT; FRT/SRT) had significantly longer median PFS (504 days, [95% confidence interval (CI): 428-580 days] vs PRT 198 days [95% CI: 62-334 days]; p = 0.006) and median OST [721 days (95% CI: 527-915 days) vs 284 days (95% CI: 0-570 days); p = 0.001]). Cats that underwent second DRT course at time of recurrence lived significantly longer than cats that received 1 RT course (either DRT or PRT [median OST 824 days (95% CI: 237-1410 days) vs 434 days (95% CI: 277-591 days); p = .028]).

Conclusion: In cats with INC, DRT is associated with prolonged OST and PFS as compared to PRT. If tumor progression occurs, a second course of DRT should be considered.
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http://dx.doi.org/10.1111/jvim.16098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995428PMC
March 2021

Treatment of genitourinary carcinoma in dogs using nonsteroidal anti-inflammatory drugs, mitoxantrone, and radiation therapy: A retrospective study.

J Vet Intern Med 2021 Mar 26;35(2):1052-1061. Epub 2021 Feb 26.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.

Background: Locoregional tumor control and prolonged survival for dogs with genitourinary carcinoma (CGUC) reportedly are achievable using treatment with radiotherapy (RT) with or without adjunctive chemotherapy and nonsteroidal anti-inflammatory drugs (NSAIDs).

Objectives: To characterize event-free and overall survival after treatment of CGUC using NSAIDs, mitoxantrone (MTX), and a standardized RT protocol (57 Gy in 20 fractions).

Animals: Fifty-one client-owned dogs treated between 2008 and 2017.

Methods: Dogs were retrospectively categorized into treatment groups: (a) first-line concurrent chemoradiotherapy (≥1 dose of MTX started within 1 month of RT); (b) first-line chemotherapy (MTX administered for >1 month before RT without tumor progression); (c) RT as a salvage procedure (MTX, surgery or both with subsequent locoregional tumor progression before RT). Treatment-induced toxicoses, event-free survival (EFS), and overall survival times (OSTs) were recorded. The influence of demographics, staging, and treatment-related factors on survival was assessed using Cox proportional hazards modeling.

Results: Median EFS and OST for all dogs were 260 and 510 days with no significant differences among groups 1 (n = 39), 2 (n = 4), and 3 (n = 8). Both EFS and OST were shorter in dogs with moderate to severe clinical signs (P < .001 and P < .001, respectively); OST was shorter in dogs with prostatic involvement (P = .02). Permanent urinary incontinence developed in 16 dogs (31%) at a median of 70 days postirradiation; other toxicoses were mild and self-limiting.

Conclusions And Clinical Importance: Mild clinical signs and lack of prostate involvement were associated with favorable prognosis for survival. Client education regarding the risk of urinary incontinence is warranted.
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http://dx.doi.org/10.1111/jvim.16078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995427PMC
March 2021

Minimally invasive ethyl cellulose ethanol ablation in domesticated cats with naturally occurring head and neck cancers: Six cats.

Vet Comp Oncol 2021 Sep 23;19(3):492-500. Epub 2021 Feb 23.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.

It is difficult to retain tumoricidal doses of ethanol in large or unencapsulated tumours without causing intoxication or damaging surrounding tissue. Ethyl cellulose-ethanol ablation (ECEA) overcomes this limitation by trapping ethanol intratumorally. To evaluate the safety of ECEA and to develop a clinically feasible workflow, a single-arm pilot study was performed in cats with lingual/sublingual squamous cell carcinoma (SCC). Six cats underwent intratumoral injection of 6% ethyl cellulose in ethanol. Subjects were observed overnight. There was mild bleeding and transient hyperthermia, and injection site pain and swelling that improved with anti-inflammatory drugs. Serum ethanol was minimally elevated; the mean concentration peaked 1 hour after injection (129 +/- 15.1 nM). Cats were rechecked at weeks 1 and 2; booster treatments were given in cats (n = 3) with stable quality of life and partial response to therapy. Recheck examinations were then performed monthly. The longest tumour dimension increased in each animal (progressive disease via cRECIST); however, estimated tumour volume was reduced in 3 of 6 cats, within 1 week of ECEA. All cats were euthanized (median survival time 70 days) because of local tumour progression and/or lingual dysfunction that was likely hastened by ECEA. ECEA is not a viable treatment for feline lingual/sublingual SCC; tumour volume was effectively reduced in some cats, but the simultaneous loss of lingual function was poorly tolerated. Further optimization may make ECEA a useful option for SCC at other oral sites in the cat, and for head and neck malignancies in other species.
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http://dx.doi.org/10.1111/vco.12687DOI Listing
September 2021
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