Publications by authors named "Rebecca Robinson"

87 Publications

Genomic, Transcriptomic, and Functional Alterations in DNA Damage Response Pathways as Putative Biomarkers of Chemotherapy Response in Ovarian Cancer.

Cancers (Basel) 2021 Mar 20;13(6). Epub 2021 Mar 20.

Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Defective DNA damage response (DDR) pathways are enabling characteristics of cancers that not only can be exploited to specifically target cancer cells but also can predict chemotherapy response. Defective Homologous Recombination Repair (HRR) function, e.g., due to BRCA1/2 loss, is a determinant of response to platinum agents and PARP inhibitors in ovarian cancers. Most chemotherapies function by either inducing DNA damage or impacting on its repair but are generally used in the clinic unselectively. The significance of HRR and other DDR pathways in determining response to several other chemotherapy drugs is not well understood. In this study, the genomic, transcriptomic and functional analysis of DDR pathways in a panel of 14 ovarian cancer cell lines identified that defects in DDR pathways could determine response to several chemotherapy drugs. Carboplatin, rucaparib, and topotecan sensitivity were associated with functional loss of HRR (validated in 10 patient-derived primary cultures) and mismatch repair. Two DDR gene expression clusters correlating with treatment response were identified, with PARP10 identified as a novel marker of platinum response, which was confirmed in The Cancer Genome Atlas (TCGA) ovarian cancer cohort. Reduced non-homologous end-joining function correlated with increased sensitivity to doxorubicin, while cells with high intrinsic oxidative stress showed sensitivity to gemcitabine. In this era of personalised medicine, molecular/functional characterisation of DDR pathways could guide chemotherapy choices in the clinic allowing specific targeting of ovarian cancers.
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http://dx.doi.org/10.3390/cancers13061420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003626PMC
March 2021

Antarctic icebergs reorganize ocean circulation during Pleistocene glacials.

Nature 2021 01 13;589(7841):236-241. Epub 2021 Jan 13.

Department of Earth Sciences, Utrecht University, Utrecht, The Netherlands.

The dominant feature of large-scale mass transfer in the modern ocean is the Atlantic meridional overturning circulation (AMOC). The geometry and vigour of this circulation influences global climate on various timescales. Palaeoceanographic evidence suggests that during glacial periods of the past 1.5 million years the AMOC had markedly different features from today; in the Atlantic basin, deep waters of Southern Ocean origin increased in volume while above them the core of the North Atlantic Deep Water (NADW) shoaled. An absence of evidence on the origin of this phenomenon means that the sequence of events leading to global glacial conditions remains unclear. Here we present multi-proxy evidence showing that northward shifts in Antarctic iceberg melt in the Indian-Atlantic Southern Ocean (0-50° E) systematically preceded deep-water mass reorganizations by one to two thousand years during Pleistocene-era glaciations. With the aid of iceberg-trajectory model experiments, we demonstrate that such a shift in iceberg trajectories during glacial periods can result in a considerable redistribution of freshwater in the Southern Ocean. We suggest that this, in concert with increased sea-ice cover, enabled positive buoyancy anomalies to 'escape' into the upper limb of the AMOC, providing a teleconnection between surface Southern Ocean conditions and the formation of NADW. The magnitude and pacing of this mechanism evolved substantially across the mid-Pleistocene transition, and the coeval increase in magnitude of the 'southern escape' and deep circulation perturbations implicate this mechanism as a key feedback in the transition to the '100-kyr world', in which glacial-interglacial cycles occur at roughly 100,000-year periods.
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http://dx.doi.org/10.1038/s41586-020-03094-7DOI Listing
January 2021

Multimodal Treatment Patterns for Osteoarthritis and Their Relationship to Patient-Reported Pain Severity: A Cross-Sectional Survey in the United States.

J Pain Res 2020 23;13:3415-3425. Epub 2020 Dec 23.

Real World Research, Adelphi Real World, Bollington, Cheshire, UK.

Purpose: The purpose of this study was to assess how patient-reported pain is related to osteoarthritis (OA) treatment patterns in routine clinical practice.

Patients And Methods: Data were collected between February and May 2017 from 153 United States (US) primary care physicians, rheumatologists, and orthopedic surgeons. Each invited up to nine consecutive patients to rate their OA pain in the last week. Physicians provided demographic, clinical, and treatment information for patients, including nonpharmacologic therapies ever recommended, currently recommended over-the-counter (OTC) medications, and currently and ever prescribed medications for the management of OA. Findings for patients with mild (0─3), moderate (4─6), and severe current pain (7─10) were compared using appropriate statistics.

Results: Among the 841 patients (61% female; mean 65 years; 57% knee OA), 45% reported mild, 36% moderate, and 19% severe current OA pain. Current treatment modalities differed by pain severity (<0.05). Most patients (70%) had been recommended nonpharmacologic therapy and 40% were currently recommended OTC medications. More patients with moderate (81%) or severe pain (78%) currently received prescription medications, with or without nonpharmacologic therapy, versus those with mild pain (67%). Overall, 47% of patients currently received just one prescription drug, while 49% had received one prescription drug ever. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most common current (58%) and ever received (88%) prescriptions. Current NSAID prescriptions were not associated with pain severity. Acetaminophen recommendations, opioid prescriptions (current and ever), and multiple prescription medications tried were numerically highest in the severe pain group (all <0.05 by pain severity). In all groups, >80% of treatment switches were due to lack of efficacy.

Conclusion: Real-life treatment patterns for OA in the US are significantly associated with current patient-reported pain. Combining nonpharmacologic and pharmacologic treatments is common but higher pain ratings are associated with multiple failed prescription treatments. Current use of acetaminophen and opioids, but not NSAIDs, increases alongside pain severity.
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http://dx.doi.org/10.2147/JPR.S285124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767791PMC
December 2020

Ixazomib, lenalidomide, and dexamethasone is effective and well tolerated in multiply relapsed (≥2nd relapse) refractory myeloma: a multicenter real world UK experience.

Leuk Lymphoma 2020 Dec 25:1-9. Epub 2020 Dec 25.

Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

There are limited real world data on ixazomib, lenalidomide, and dexamethasone (IRd) in multiply relapsed myeloma. We analyzed outcomes of 116 patients who received IRd predominantly at second and subsequent relapse including those refractory to proteasome inhibitors (PIs). With a median follow up 16.3 months, the overall response rate was 66.9%; median progression-free survival (PFS) was 17.7 months with median overall survival (OS) not reached (NR). PFS and OS were significantly shorter in advanced disease (PFS; 12.6 vs. 21.2 months ( = .01), OS; 15.9 months vs. NR ( = .01) for ISS3 vs. ISS 1&2, respectively). PFS and OS were significantly shorter in clinical high risk (CHR) compared to standard risk (SR) patients (PFS; 9.3 months vs. NR ( = .001), OS; 11.5 months vs. NR ( < .001), respectively). There was a trend toward shorter PFS in PI-refractory patients 13.7 vs. 19.6 months for non-PI refractory ( = .2). The triplet combination was generally well tolerated.
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http://dx.doi.org/10.1080/10428194.2020.1864355DOI Listing
December 2020

Pain severity and healthcare resource utilization in patients with osteoarthritis in the United States.

Postgrad Med 2021 Jan 4;133(1):10-19. Epub 2020 Dec 4.

Real World Research, Adelphi Real World , Bollington, UK.

Objective: To evaluate healthcare resource utilization (HCRU) by osteoarthritis (OA) pain severity.

Methods: Cross-sectional surveys of US physicians and their patients were conducted between February and May 2017. Using the Numeric Rating Scale, patients were classified by self-reported pain intensity in the last week into mild (0-3), moderate (4-6), and severe (7-10) cohorts. Parameters assessed included clinical characteristics, HCRU, and current caregiver support. Descriptive statistics were obtained, and analysis of variance and chi-square tests were performed.

Results: Patients (n = 841) were mostly female (60.9%) and white (77.8%), with mean age of 64.6 years. Patients reported mild (45.4%), moderate (35.9%), and severe (18.7%) OA pain. Mean number of affected joints varied by pain severity (range mild: 2.7 to severe: 3.6; < 0.0001). Pain severity was associated with an increased number of physician-reported and patient-reported overall healthcare provider visits (HCPs; both < 0.001). As pain increased, patients reported an increased need for mobility aids, accessibility modifications to homes, and help with daily activities due to functional disability. The number of imaging tests used to diagnose OA was similar across pain severity but varied when used for monitoring (X-rays: < 0.0001; computerized tomography scans: < 0.0447). Hospitalization rates for OA were low but were significantly associated with pain severity (mild: 4.9%; severe: 11.5%). Emergency department visits were infrequent but increasing pain severity was associated with more prior and planned surgeries.

Conclusion: Greater current pain was associated with more prior HCRU including imaging for monitoring progression, HCP visits including more specialty care, hospitalizations, surgery/planned surgery, and loss of independence due to functional disability. Yet rates of hospitalizations and X-ray use were still sizable even among patients with mild pain. These cross-sectional findings warrant longitudinal assessment to further elucidate the impact of pain on HCRU.
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http://dx.doi.org/10.1080/00325481.2020.1841988DOI Listing
January 2021

Comparison of two topical treatments of gastro-oesophageal regurgitation in dogs during general anaesthesia.

Vet Anaesth Analg 2020 Sep 21;47(5):672-675. Epub 2020 May 21.

Davies Veterinary Specialists, Higham Gobion, Hitchin, UK.

Objective: To determine whether suction, lavage and instillation of sodium bicarbonate, following a gastro-oesophageal regurgitation event under general anaesthesia, would alter oesophageal pH to a greater degree than when lavage was not used.

Study Design: Prospective, randomised, clinical study.

Animals: A group of 22 client-owned dogs.

Methods: Dogs presenting with gastro-oesophageal regurgitation (GOReg) under general anaesthesia were randomised into groups: no lavage (G1) or lavage (G2). All dogs underwent oesophageal suctioning until no further regurgitant material was retrieved. Dogs in G2 had oesophageal lavage with tap water until the suctioned water was clear. All dogs then had 4.2% sodium bicarbonate (0.6 mL kg) instilled into the oesophagus. An oesophageal pH probe was placed to record pH immediately after: GOReg (T1), suctioning (T2), lavage of the oesophagus (T3; G2 only) and sodium bicarbonate instillation (T4). Categorical data were analysed using Fisher's exact test, and continuous data were analysed using either the two-sample t-test or the Wilcoxon rank-sum test. Parametric data are reported as mean ± standard deviation and non-parametric data as median (interquartile range). A p value < 0.05 was considered significant.

Results: Oesophageal pH was low in both groups immediately after GOReg [G1: 2.95 (2.20-4.18), G2: 3.29 (1.41-4.03)] but oesophageal pH was not significantly different between groups at T1, T2 and T4. Oesophageal lavage significantly increased pH but the overall change in pH following bicarbonate administration (T2-T4) was not significantly different between groups [G1: 3.16 ± 1.52, G2: 3.52 ± 1.47]. No adverse events following GOReg were recorded.

Conclusions And Clinical Relevance: Both groups had similar and clinically important increases in oesophageal pH. Although oesophageal lavage increased pH, this did not affect the final oesophageal pH when sodium bicarbonate was instilled and therefore may be an unnecessary step.
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http://dx.doi.org/10.1016/j.vaa.2020.04.010DOI Listing
September 2020

The Utility of the Sit-to-Stand Test for Inpatients in the Acute Hospital Setting After Lung Transplantation.

Phys Ther 2020 07;100(7):1217-1228

Physiotherapy Department, The Alfred, Alfred Health, Monash University and La Trobe University.

Objective: Measurement of physical function is important to guide physical therapy for patients post-lung transplantation (LTx). The Sit-to-Stand (STS) test has proven utility in chronic disease, but psychometric properties post-LTx are unknown. The study aimed to assess reliability, validity, responsiveness, and feasibility of the 60-second STS post-LTx.

Methods: This was a measurement study in 62 inpatients post-LTx (31 acute postoperative; 31 medical readmissions). Interrater reliability was assessed with 2 STS tests undertaken by different assessors at baseline. Known group validity was assessed by comparing STS repetitions in postoperative and medical groups. Content validity was assessed using comparisons to knee extensor and grip strength, measured with hand-held dynamometry. Criterion validity was assessed by comparison of STS repetitions and 6-minute walk distance postoperatively. Responsiveness was assessed using effect sizes over inpatient admission.

Results: Median (interquartile range) age was 62 (56-67) years; time post-LTx was 5 (5-7) days postoperative and 696 (244-1849) days for medical readmissions. Interrater reliability was excellent (intraclass correlation coefficient type 2,1 = 0.96), with a mean learning effect of 2 repetitions. Repetitions were greater for medical at baseline (mean 18 vs 8). More STS repetitions were associated with greater knee extensor strength (postoperative r = 0.57; medical r = 0.47) and 6-minute walk distance (postoperative r = 0.68). Effect sizes were 0.94 and 0.09, with a floor effect of 23% and 3% at baseline (postoperative/medical) improving to 10% at discharge. Patients incapable of attempting a STS test were excluded, reducing generalizability to critical care. Physical rehabilitation was not standardized, possibly reducing responsiveness.

Conclusions: The 60-second STS demonstrated excellent interrater reliability and moderate validity and was responsive to change postoperatively.

Impact: The 60-second STS represents a safe, feasible functional performance tool for inpatients post-LTx. Two tests should be completed at each time point.
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http://dx.doi.org/10.1093/ptj/pzaa057DOI Listing
July 2020

Costs of Early Stage Alzheimer's Disease in the United States: Cross-Sectional Analysis of a Prospective Cohort Study (GERAS-US)1.

J Alzheimers Dis 2020 ;75(2):437-450

Geriatric Medicine, Palliative Care and Neuroscience, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Costs associated with early stages of Alzheimer's disease (AD; mild cognitive impairment [MCI] and mild dementia [MILD]) are understudied.

Objective: To compare costs associated with MCI and MILD due to AD in the United States.

Methods: Data included baseline patient/study partner medical history, healthcare resource utilization, and outcome assessments as part of a prospective cohort study. Direct, indirect, and total societal costs were derived by applying standardized unit costs to resources for the 1-month pre-baseline period (USD2017). Costs/month for MCI and MILD cohorts were compared using analysis of variance models. To strengthen the confidence of diagnosis, amyloid-β (Aβ) tests were included and analyses were replicated stratifying within each cohort by amyloid status [+ /-].

Results: Patients (N = 1327) with MILD versus MCI had higher total societal costs/month ($4243 versus $2816; p < 0.001). These costs were not significantly different within each severity cohort by amyloid status. The largest fraction of overall costs were informal caregiver costs (45.1%) for the MILD cohort, whereas direct medical patient costs were the largest for the MCI cohort (39.0%). Correspondingly, caregiver time spent on basic activities of daily living (ADLs), instrumental ADLs, and supervision time was twice as high for MILD versus MCI (all p < 0.001).

Conclusion: Early AD poses a financial burden, and despite higher functioning among those with MCI, caregivers were significantly impacted. The major cost driver was the patient's clinical cognitive-functional status and not amyloid status. Differences were primarily due to rising need for caregiver support.
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http://dx.doi.org/10.3233/JAD-191212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306889PMC
May 2021

The test accuracy of antenatal ultrasound definitions of fetal macrosomia to predict birth injury: A systematic review.

Eur J Obstet Gynecol Reprod Biol 2020 Mar 16;246:79-85. Epub 2020 Jan 16.

Division of Child Health, Obstetrics and Gynaecology, School of Medicine, University of Nottingham, United Kingdom.

Objectives: To determine which ultrasound measurement for predicted fetal macrosomia most accurately predicts adverse delivery and neonatal outcomes.

Study Design: Four biomedical databases searched for studies published after 1966. Randomised trials or observational studies of women with singleton pregnancies, resulting in a term birth who have undergone an index test of interest measured and recorded as predicted fetal macrosomia ≥28 weeks. Adverse outcomes of interest included shoulder dystocia, brachial plexus injury (BPI) and Caesarean section.

Results: Twenty-five observational studies (13,285 participants) were included. For BPI, the only significant positive association was found for Abdominal Circumference (AC) to Head Circumference (HC) difference > 50 mm (OR 7.2, 95 % CI 1.8-29). Shoulder dystocia was significantly associated with abdominal diameter (AD) minus biparietal diameter (BPD) ≥ 2.6 cm (OR 4.2, 95 % CI 2.3-7.5, PPV 11 %) and AC > 90th centile (OR 2.3, 95 % CI 1.3-4.0, PPV 8.6 %) and an estimated fetal weight (EFW) > 4000 g (OR 2.1 95 %CI 1.0-4.1, PPV 7.2 %).

Conclusions: Estimated fetal weight is the most widely used ultrasound marker to predict fetal macrosomia in the UK. This study suggests other markers have a higher positive predictive value for adverse outcomes associated with fetal macrosomia.
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http://dx.doi.org/10.1016/j.ejogrb.2020.01.019DOI Listing
March 2020

Eco-evolutionary feedbacks link prey adaptation to predator performance.

Biol Lett 2019 11 20;15(11):20190626. Epub 2019 Nov 20.

Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, CA 95060, USA.

Eco-evolutionary feedbacks may determine the outcome of predator-prey interactions in nature, but little work has been done to quantify the feedback effect of short-term prey adaptation on predator performance. We tested the effects of prey availability and recent (less than 100 years) prey adaptation on the feeding and growth rate of largemouth bass (), foraging on western mosquitofish (). Field surveys showed higher densities and larger average body sizes of mosquitofish in recently introduced populations without bass. Over a six-week mesocosm experiment, bass were presented with either a high or low availability of mosquitofish prey from recently established populations either naive or experienced with bass. Naive mosquitofish were larger, less cryptic and more vulnerable to bass predation compared to their experienced counterparts. Bass consumed more naive prey, grew more quickly with naive prey, and grew more quickly per unit biomass of naive prey consumed. The effect of mosquitofish history with the bass on bass growth was similar in magnitude to the effect of mosquitofish availability. In showing that recently derived predation-related prey phenotypes strongly affect predator performance, this study supports the presence of reciprocal predator-prey trait feedbacks in nature.
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http://dx.doi.org/10.1098/rsbl.2019.0626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892525PMC
November 2019

Observation of Patient and Caregiver Burden Associated with Early Alzheimer's Disease in the United States: Design and Baseline Findings of the GERAS-US Cohort Study1.

J Alzheimers Dis 2019 ;72(1):279-292

Geriatric Medicine, Palliative Care and Neuroscience, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Alzheimer's disease (AD) is one of the costliest diseases in the United States.

Objective: To describe aspects of real-world patient and caregiver burden in patients with clinician-diagnosed early AD, including mild cognitive impairment (MCI) and mild dementia (MILD) due to AD.

Methods: Cross-sectional assessment of GERAS-US, a 36-month cohort study of patients seeking care for early AD. Eligible patients were categorized based on study-defined categories of MCI and MILD and by amyloid positivity [+] or negativity [-] within each severity cohort. Demographic characteristics, health-related outcomes, medical history, and caregiver burden by amyloid status are described.

Results: Of 1,198 patients with clinician-diagnosed early AD, 52% were amyloid[+]. For patients in both cohorts, amyloid[-] was more likely to occur in those with: delayed time to an AD-related diagnosis, higher rates of depression, poorer Bath Assessment of Subjective Quality of Life in Dementia scores, and Hispanic/Latino ethnicity (all p < 0.05). MILD[-] patients (versus MILD[+]) were more medically complex with greater rates of depression (55.7% versus 40.4%), sleep disorders (34.3% versus 26.5%), and obstructive pulmonary disease (11.8% versus 6.6%); and higher caregiver burden (Zarit Burden Interview) (all p < 0.05). MILD[+] patients had lower function according to the Functional Activities Questionnaire (p < 0.001), yet self-assessment of cognitive complaints across multiple measures did not differ by amyloid status in either severity cohort.

Conclusions: Considerable patient and caregiver burden was observed in patients seeking care for memory concerns. Different patterns emerged when both disease severity and amyloid status were evaluated underscoring the need for further diagnostic assessment and care for patients.Study Registry:H8A-US-B004; ClinicalTrials.gov: NCT02951598.
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http://dx.doi.org/10.3233/JAD-190430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839598PMC
November 2020

Lifestyle medicine and physical activity knowledge of final year UK medical students.

BMJ Open Sport Exerc Med 2019 14;5(1):e000518. Epub 2019 Jun 14.

Centre for Health and Human Performance, London, UK.

Objectives: It has previously been reported in the that final year UK medical students are lacking knowledge of the physical activity guidelines. This study assesses whether the knowledge and training of final year UK medical students has improved, whether knowledge correlates with lifestyle choices and whether there is a need for lifestyle medicine training, which includes physical activity guidance, to be offered to this cohort.

Methods: A questionnaire consisting of nine key questions was sent to 1356 final year medical students from seven different UK medical schools.

Results: Completed questionnaires (n=158) were analysed and revealed that 52% were unaware of the current exercise guidelines in the UK. 80% stated they had not received training in lifestyle medicine over the last 2 years while 48.1% were unacquainted with motivational interviewing. 76% wanted more lifestyle medicine teaching to be incorporated into the medical school curriculum.

Conclusions: These findings suggest that final year UK medical students still lack knowledge of the physical activity guidelines. In addition, there is a demand among this cohort for increased lifestyle medicine training which may in turn be an effective way of improving physical activity knowledge.
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http://dx.doi.org/10.1136/bmjsem-2019-000518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579569PMC
June 2019

Effect of benzodiazepines on the dose of alfaxalone needed for endotracheal intubation in healthy dogs.

Vet Anaesth Analg 2018 Nov 29;45(6):720-728. Epub 2018 Jul 29.

Animal Health Trust, Small Animal Centre, Newmarket, Suffolk, UK.

Objective: To evaluate the dose-sparing effect of midazolam or diazepam on the dose of alfaxalone required to achieve endotracheal intubation in premedicated dogs.

Study Design: Prospective, randomized, 'blinded', controlled clinical trial.

Animals: Ninety healthy dogs anaesthetized for elective surgery or diagnostic procedures.

Methods: Saline (0.1 mL kg), or midazolam or diazepam (0.2, 0.3, 0.4 or 0.5 mg kg) intravenously (IV) was randomly assigned; investigators were unaware of group designation. After premedication with IV acepromazine 0.01 mg kg and methadone 0.2 mg kg, the degree of sedation was assessed. Alfaxalone (0.5 mg kg) was administered IV, followed by the assigned treatment. Further alfaxalone was administered until endotracheal intubation could be performed. Ease of endotracheal intubation, pulse rate and arterial blood pressure were assessed. General linear models were used to examine the effect of treatment drug and dose on induction dose of alfaxalone with Tukey's post hoc tests. Incidence of adverse reactions was assessed with chi-square tests.

Results: There were no significant differences between groups with regard to demographic data or sedation. Median (range) induction dose of alfaxalone in the saline group was 0.74 (0.43-1.26) mg kg compared with 0.5 (0.46-0.75) mg kg and 0.5 (0.42-1.2) mg kg for the midazolam and diazepam groups, respectively. Midazolam 0.3 and 0.5 mg kg (p = 0.005 and 0.044, respectively) and diazepam 0.4 mg kg (p = 0.032) reduced the alfaxalone dose compared with saline. Adverse effects were not significantly different between groups. Midazolam 0.2, 0.3, 0.4 and 0.5 mg kg (p < 0.044, p = 0.001, p = 0.007, p = 0.044, respectively) and diazepam 0.2 and 0.5 mg kg (p = 0.025 and p = 0.025) improved intubation score compared with saline.

Conclusion And Clinical Relevance: Midazolam 0.3 and 0.5 mg kg and diazepam 0.4 mg kg coadministered at anaesthetic induction allow alfaxalone dose reduction in healthy dogs. Use of benzodiazepines improved the ease of endotracheal intubation.
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http://dx.doi.org/10.1016/j.vaa.2018.06.011DOI Listing
November 2018

Clozapine is associated with secondary antibody deficiency.

Br J Psychiatry 2018 Sep 27:1-7. Epub 2018 Sep 27.

Professor of Clinical Immunology,Immunodeficiency Centre for Wales,University Hospital of Wales,UK.

Background: Schizophrenia affects 1% of the population. Clozapine is the only medication licensed for treatment-resistant schizophrenia and is intensively monitored to prevent harm from neutropenia. Clozapine is also associated with increased risk of pneumonia although the mechanism is poorly understood.AimsTo investigate the potential association between clozapine and antibody deficiency.

Methods: Patients taking clozapine and patients who were clozapine-naive and receiving alternative antipsychotics were recruited and completed a lifestyle, medication and infection-burden questionnaire. Serum total immunoglobulins (immunoglobulin (Ig)G, IgA, IgM) and specific IgG antibodies to haemophilus influenzae type B, tetanus and IgG, IgA and IgM to pneumococcus were measured.

Results: Immunoglobulins were all significantly reduced in the clozapine-treated group (n = 123) compared with the clozapine-naive group (n = 111). Odds ratios (ORs) for a reduction in clozapine:control immunoglobulin values below the fifth percentile were IgG, OR = 6.00 (95% CI 1.31-27.44); IgA, OR = 16.75 (95% CI 2.18-128.60); and IgM, OR = 3.26 (95% CI 1.75-6.08). These findings remained significant despite exclusion of other potential causes of hypogammaglobulinaemia. In addition, duration on clozapine was associated with decline in IgG. A higher proportion of the clozapine-treated group reported taking more than five courses of antibiotics in the preceding year (5.3% (n = 5) versus 1% (n = 1).

Conclusions: Clozapine use was associated with significantly reduced immunoglobulin levels and an increased proportion of patients using more than five antibiotic courses in a year. Antibody testing is not included in existing clozapine monitoring programmes but may represent a mechanistic explanation and modifiable risk factor for the increased rates of pneumonia and sepsis-related mortality previously reported in this vulnerable cohort.Declaration of interestS.J. has received support from CSL Behring, Shire, LFB, Biotest, Binding Site, Sanofi, GSK, UCB Pharma, Grifols, BPL SOBI, Weatherden, Zarodex and Octapharma for projects, advisory boards, meetings, studies, speaker and clinical trials.
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http://dx.doi.org/10.1192/bjp.2018.152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429246PMC
September 2018

Health Care Utilization and Direct Costs Among Patients Diagnosed with Cluster Headache in U.S. Health Care Claims Data.

J Manag Care Spec Pharm 2018 Sep;24(9):921-928

1 Eli Lilly and Company, Indianapolis, Indiana.

Background: Cluster headache (CH) is a rare trigeminal cephalalgia that is associated with extremely painful unilateral headache attacks and autonomic symptoms. Attacks may be episodic or chronic and associated with substantial suffering due to excruciating pain and limited treatment options. Frequent cluster headaches cause substantial burden for patients, resulting in reduced productivity caused by disability, as well as direct costs in some European countries. Less is known, however, about direct costs of recurring health care resource utilization (HCRU) in the United States.

Objective: To characterize HCRU and direct costs associated with CH in the United States from a third-party payer perspective.

Methods: This retrospective observational study analyzed claims data from the Truven Health Analytics MarketScan Research Databases from 2009-2014. Two cohorts were compared: CH (> 2 diagnostic CH claims) and controls (nonheadache patients). All patients were enrolled continuously for ± 12 months from date of first CH claim. HCRU and direct costs were examined during 12 months post-index as all-cause and CH-specific. Cost and HCRU differences were compared using propensity score-adjusted bin bootstrapping.

Results: CH and control cohorts comprised 6,562 and 143,761 patients (aged ≥ 18 years), respectively. Post-index, 36.9% of CH patients versus 16.2% of controls were admitted to the emergency department (ED), and 14.8% versus 6.1% were hospitalized for any reason, respectively (each P < 0.001). CH patients had a 2- to 3-fold significantly greater number of all-cause mean claims for outpatient visits (26.5 vs. 12.4 visits), hospital visits (0.2 vs. 0.1 visits), and ED visits (1.0 vs. 0.3 visits) versus controls (all P < 0.001). The mean number of all-cause visits with reported radiology and laboratory claims was 1.5- to 2.0-fold greater in CH patients versus controls (each P < 0.001). Mean total direct costs for all-cause claims were more than 2-fold greater in post-index ($16,530) for CH patients versus controls ($7,197, P < 0.0001). Similarly, mean direct all-cause costs attributable to outpatient, inpatient, and pharmacy claims were significantly (2-fold) greater; radiology and ED claims were 3- to 4-fold greater among CH patients versus controls (all P < 0.001). However, CH was cited infrequently as a reason for HCRU, indicating that comorbid conditions may substantially increase HCRU in CH patients. The most common reasons for ED admission in CH patients were gastric ulcer with hemorrhage, sub-arachnoid hemorrhage, and headache symptoms. The most common hospital discharge diagnoses for CH patients not observed in top 10 reasons in controls included cerebral artery occlusion/unspecified with cerebral infarction, headache symptoms, syncope/collapse, and diverticulitis.

Conclusions: These findings suggest that, from a payer perspective, CH patients incur significantly higher health care costs versus controls. However, these high costs were not exclusively headache-related. Extrapolating our cost findings to estimated U.S. prevalence rates, approximate total direct cost for CH is greater than $2.8 billion/year.

Disclosures: Eli Lilly and Company was the sole sponsor and funder for this study and was responsible for the study design, data collection, data analysis, interpretation of data, and decision to publish the findings. All authors are employees and minor stockholders of Eli Lilly and Company.
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http://dx.doi.org/10.18553/jmcp.2018.24.9.921DOI Listing
September 2018

Dual diagnosis competencies: A systematic review of staff training literature.

Addict Behav Rep 2018 Jun 2;7:53-57. Epub 2018 Feb 2.

Neami National, Melbourne, Australia.

Objective: To conduct a systematic review of the literature regarding approaches to staff training in dual diagnosis competencies.

Methods: A search was conducted using eight databases: Informit, Taylor & Francis, Springer, Proquest, Expand, Sage, Psych info, Elsevier and Cinahl. The year range was 2005 to April 2015. An additional manual search of reference lists was conducted to ensure relevant articles were not overlooked.

Results: Of 129 potential results, there were only 11 articles regarding staff training in dual diagnosis. The limited studies included problems: small sample sizes, selection biases, and questions as to validity of some capability instruments, and low inclusion of service user perspectives. Organisational challenges to greater uptake of staff training including agency size, agency willingness to change, and a need to change policies.

Conclusions: There is a pressing need for more research, and quality research, in this important area of knowledge translation, dissemination and implementation of evidence-based practices. In particular there is limited literature regarding the efficacy of dual diagnosis competency resources, and a gap as to use of the mentoring in dual diagnosis capacity building.
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http://dx.doi.org/10.1016/j.abrep.2018.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993964PMC
June 2018

Side Streets and U-Turns: Effects of Context Switching, Direction Switching, and Factor Switching on Interitem Correlations and Misresponse Rates.

J Pers Assess 2019 May-Jun;101(3):326-339. Epub 2018 Apr 13.

a Department of Psychology , University of Texas at Arlington.

This study tested implications of the context switching perspective proposed by Hamby, Ickes, and Babcock ( 2016 ). Using trained raters to assess the amount of reframing required to interpret the meaning of the subsequent (second) item within all adjacent item pairs, we first established that this process variable could be measured reliably. Then, in the data for 18 personality measures drawn from 3 individual-difference domains, we found that the amount of reframing (i.e., context switching) needed to interpret successive items predicted both lower interitem correlations and a greater percentage of misresponders. Similarly, item pairs that were mismatched in "directional" wording also predicted both lower interitem correlations and more misresponders. Finally, item pairs representing different factors predicted lower interitem correlations. Although the effects of direction switching and factor switching were partially mediated by the amount of reframing required, they remained significant even when the mediating effect of reframing was statistically controlled. These results indicate that interpreting the meaning of test items is a task for which the level of difficulty can vary with each successive item, as a function of how the current item compares to the previous item in aspects such as its context generality or specificity, directional wording, and content domain.
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http://dx.doi.org/10.1080/00223891.2018.1450262DOI Listing
March 2020

The timing and extent of acute physiotherapy involvement following lung transplantation: An observational study.

Physiother Res Int 2018 Jul 12;23(3):e1710. Epub 2018 Mar 12.

Monash University, Melbourne, Australia.

Background And Purpose: Physiotherapy "standard care" for the acute post lung transplant recipient has not yet been documented. We aimed to analyse how soon patients commence exercise and how much time is dedicated to this during physiotherapy sessions acutely post lung transplantation.

Methods: Prospective observational study of bilateral sequential and single lung transplant recipients for any indication, ≥18 years. Participants were observed during 6 physiotherapy sessions: 3 initial and 3 prior to acute inpatient discharge. Duration and content of each session was recorded, consisting of physical exercise and non-exercise tasks.

Results: Thirty participants, 20 male, median age 58.5 (interquartile range 54.5-65.0) were observed over 173 sessions. Chronic obstructive pulmonary disease was the most common transplant indication (n = 12, 40%). Bilateral lung transplant was performed in 90% (n = 27) of participants. First time to mobilise was 2 (2-3) days. Participants received 14 (12.8-23.8) sessions over 18 (17-31) days. The mean duration of physiotherapy in the initial phase was 107.8 (standard deviation 21.8) min, with 22.9 (7.5) min spent exercising. In the final phase, exercise time increased to 28.1 (11.4) min out of 84.1 (24.6) min. Assessment was the most common non-exercise component, at 26.6 (7.9) and 22.1 (12.5) min across the three initial and final sessions.

Implications For Physiotherapy Practice: Lung transplant recipients spent 21-34% of observed sessions performing physical exercise beginning 48 hr following surgery. Remaining physiotherapist time was spent on assessment, respiratory interventions, education, and patient-specific duties. The use of physiotherapy assistants, structured, progressive exercise programs, and continued workplace innovation may enable a higher percentage of physiotherapist supervised physical exercise in the future.
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http://dx.doi.org/10.1002/pri.1710DOI Listing
July 2018

Clinical Characteristics and Treatment Patterns Among Patients Diagnosed With Cluster Headache in U.S. Healthcare Claims Data.

Headache 2017 Oct 5;57(9):1359-1374. Epub 2017 Jun 5.

Eli Lilly and Company, Indianapolis, IN, USA.

Objective: To characterize demographics, clinical characteristics, and treatment patterns of patients with cluster headache (CH).

Background: CH is an uncommon trigeminal autonomic cephalalgia with limited evidence-based treatment options. Patients suffer from extremely painful unilateral headache attacks and autonomic symptoms with episodic and chronic cycles.

Design/methods: This retrospective analysis used insurance claims from Truven Health Analytics MarketScan research databases from 2009 to 2014. Two cohorts were compared: CH patients (with ≥2 CH claims) were propensity score matched with 4 non-headache controls, all with continuous enrollment for 12 months before and after the date of first CH claim or matched period among controls.

Results: CH patients (N = 7589) were mainly male (57.4%) and 35-64 years old (73.2%), with significantly more claims for comorbid conditions vs controls (N = 30,341), including depressive disorders (19.8% vs 10.0%), sleep disturbances (19.7% vs 9.1%), anxiety disorders (19.2% vs 8.7%), and tobacco use disorders (12.8% vs 5.3%), with 2.5 times greater odds of suicidal ideation (all P < .0001). Odds of drug dependence were 3-fold greater among CH patients (OR = 2.8 [95% CI 2.3-3.4, P < .0001]). CH patients reported significantly greater use of prescription medications compared with controls; 25% of CH patients had >12 unique prescription drug claims. Most commonly prescribed drug classes for CH patients included: opiate agonists (41%), corticosteroids (34%), 5HT-1 agonists (32%), antidepressants (31%), NSAIDs (29%), anticonvulsants (28%), calcium antagonists (27%), and benzodiazepines (22%). Only 30.4% of CH patients received recognized CH treatments without opioids during the 12-month post-index period. These patients were less likely to visit emergency departments or need hospitalizations (26.8%) as compared to CH patients with no pharmacy claims for recognized CH treatments or opioids (33.6%; P < .0001).

Conclusions: The burden of CH is associated with significant co-morbidity, including substance use disorders and suicidal ideation, and treatment patterns indicating low use of recognized CH treatments.
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http://dx.doi.org/10.1111/head.13127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655925PMC
October 2017

Change in non-abstinent WHO drinking risk levels and alcohol dependence: a 3 year follow-up study in the US general population.

Lancet Psychiatry 2017 06 26;4(6):469-476. Epub 2017 Apr 26.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.

Background: Alcohol dependence is often untreated. Although abstinence is often the aim of treatment, many drinkers prefer drinking reduction goals. Therefore, if supported by evidence of benefit, drinking reduction goals could broaden the appeal of treatment. Regulatory agencies are considering non-abstinent outcomes as efficacy indicators in clinical trials, including reduction in WHO drinking risk levels-very high, high, moderate, and low-defined in terms of mean ethanol consumption (in grams) per day. We aimed to study the relationship between reductions in WHO drinking risk levels and subsequent reduction in the risk of alcohol dependence.

Methods: In this population-based cohort study, we included data from 22 005 drinkers who were interviewed in 2001-02 (Wave 1) and re-interviewed 3 years later (2004-05; Wave 2) in the US National Epidemiologic Survey on Alcohol and Related Conditions. Alcohol consumption (WHO drinking risk levels) and alcohol dependence (at least three of seven DSM-IV criteria in the previous 12 months) were assessed at both waves. We used logistic regression to test the relationship between change in WHO drinking risk levels between Waves 1 and 2, and alcohol dependence at Wave 2.

Findings: At Wave 1, 2·5% (weighted proportion) of the respondents were very-high-risk drinkers, 2·5% were high-risk drinkers, 4·8% were moderate-risk drinkers, and most (90·2%) were low-risk drinkers. Reduction in WHO drinking risk level predicted significantly lower odds of alcohol dependence at Wave 2, particularly among very-high-risk drinkers (adjusted odds ratios 0·27 [95% CI 0·18-0·41] for reduction by one level, 0·17 [0·10-0·27] for two levels, and 0·07 [0·05-0·10] for three levels) and high-risk drinkers (0·64 [0·54-0·75] for one level and 0·12 [0·09-0·15] for two levels), and among those with alcohol dependence at Wave 1 (0·29 [0·15-0·57] for one level, 0·06 [0·04-0·10] for two levels, and 0·04 [0·03-0·06] for three levels in very-high-risk drinkers).

Interpretation: Our results support the use of reductions in WHO drinking risk levels as an efficacy outcome in clinical trials. Because these risk levels can be readily translated into standard drink equivalents per day of different countries, the WHO risk levels could also be used internationally to guide treatment goals and clinical recommendations on drinking reduction.

Funding: US National Institute on Alcohol Abuse and Alcoholism, New York State Psychiatric Institute, the Alcohol Clinical Trials Initiative.
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http://dx.doi.org/10.1016/S2215-0366(17)30130-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536861PMC
June 2017

Anesthesia Case of the Month.

J Am Vet Med Assoc 2017 Jan;250(2):169-172

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http://dx.doi.org/10.2460/javma.250.2.169DOI Listing
January 2017

Variations in the management of fibromyalgia by physician specialty: rheumatology versus primary care.

Pragmat Obs Res 2016 20;7:11-20. Epub 2016 May 20.

Department of Family Medicine, University of California at San Diego School of Medicine, San Diego, CA, USA.

Purpose: To evaluate the effect of physician specialty regarding diagnosis and treatment of fibromyalgia (FM) and assess the clinical status of patients initiating new treatment for FM using data from Real-World Examination of Fibromyalgia: Longitudinal Evaluation of Costs and Treatments.

Patients And Methods: Outpatients from 58 sites in the United States were enrolled. Data were collected via in-office surveys and telephone interviews. Pairwise comparisons by specialty were made using chi-square, Fisher's exact tests, and Student's -tests.

Results: Physician specialist cohorts included rheumatologists (n=54), primary care physicians (n=25), and a heterogeneous group of physicians practicing pain or physical medicine, psychiatry, neurology, obstetrics and gynecology, osteopathy, or an unspecified specialty (n=12). The rheumatologists expressed higher confidence diagnosing FM (4.5 on a five-point scale) than primary care physicians (4.1) (=0.037). All cohorts strongly agreed that recognizing FM is their responsibility. They agreed that psychological aspects of FM are important, but disagreed that symptoms are psychosomatic. All physician cohorts agreed with a multidisciplinary approach including nonpharmacological and pharmacological treatments, although physicians were more confident prescribing medications than alternative therapies. Most patients reported moderate to severe pain, multiple comorbidities, and treatment with several medications and nonpharmacologic therapies.

Conclusion: Physician practice characteristics, physician attitudes, and FM patient profiles were broadly similar across specialties. The small but significant differences reported by physicians and patients across physician cohorts suggest that despite published guidelines, treatment of FM still contains important variance across specialties.
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http://dx.doi.org/10.2147/POR.S79441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085275PMC
May 2016

Clinical Impact of Not Achieving Recommended Dose on Duration of Atomoxetine Treatment in Adults with Attention-Deficit/Hyperactivity Disorder.

CNS Neurosci Ther 2016 12 31;22(12):970-978. Epub 2016 Jul 31.

Lilly USA LLC, Indianapolis, IN, USA.

Aim: To compare atomoxetine (ATX) length of therapy (LoT) among adults with ADHD who reached the recommended dose of 80 mg/day (ATX ≥ 80) versus those who did not (ATX < 80) analyzed separately in patients prescribed ATX as monotherapy (mono) and in combination with other ADHD medications (combo).

Methods: This was a retrospective observational cohort study of the Truven Health Marketscan Commercial Claims Database from January 1, 2006-September 30, 2013, with a 6-month preindex period free of ATX (1st ATX claim as index event) and a 1-year follow-up. LoT during follow-up was calculated using prescription claim fill dates and included all days with medication on hand regardless of treatment gaps.

Results: Only 45.0% of the 36,076 mono and 77.9% of the 1548 combo patients reached an ATX dose of ≥80 mg/day in 1-year follow-up. When patients filled at least one 80 mg prescription, their total days of therapy over the course of a year were significantly greater than if they did not (mono: 159.3 vs. 65.6 days; combo: 237.4 vs. 172.0; P < 0.0001). Across all timepoints examined (Day 14, 30, 60, 90, 210) for mono and combo, ATX ≥ 80 versus ATX < 80 patients had greater mean doses (P < 0.0001). Combo patients had longer ATX LoT than mono patients regardless if they reached 80 mg or not (P < 0.0001), but mono patients LoT was 93.8 days longer for ATX ≥ 80 versus ATX < 80 patients compared to 65.5 days for combo patients. Of patients reaching 80 mg/day, 71.7% of mono and 62.8% of combo patients did so by Day 30. For mono ATX ≥ 80 and ATX < 80 patients, LoT was significantly (P < 0.0001) less in previously treated patients compared to naive patients.

Conclusion: Ensuring adult ADHD patients are treated with ATX at a target dose of 80 mg/day is an important clinical consideration for maximizing patient days on therapy, which can be important for treatment optimization.
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http://dx.doi.org/10.1111/cns.12595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129573PMC
December 2016

Covariates of depression and high utilizers of healthcare: Impact on resource use and costs.

J Psychosom Res 2016 06 13;85:35-43. Epub 2016 Apr 13.

HealthCore, Inc., Wilmington, DE, United States.

Objective: To characterize healthcare costs, resource use, and treatment patterns of survey respondents with a history of depression who are high utilizers (HUds) of healthcare and to identify factors associated with high utilization.

Methods: Adults with two or more depression diagnoses identified from the HealthCore Integrated Research Database were invited to participate in the CODE study, which links survey data with 12-month retrospective claims data. Patient surveys provided data on demographics, general health, and symptoms and/or comorbidities associated with depression. Similar clinical conditions also were identified from the medical claims. Factors associated with high utilization were identified using logistic regression models.

Results: Of 3132 survey respondents, 1921 were included, 193 of whom were HUds (defined as those who incurred the top 10% of total all-cause costs in the preceding 12months). Mean total annual healthcare costs were eightfold greater for HUds than for non-HUds ($US56,145 vs. $US6,954; p<.0001). HUds incurred more inpatient encounters (p<.0001) and emergency department (p=.01) and physician office visits (p<.0001). Similar findings were observed for mental healthcare costs/resource use. HUds were prescribed twice as many medications (total mean: 16.86 vs. 8.32; psychotropic mean: 4.11 vs. 2.61; both p<.0001). HUds reported higher levels of depression severity, fatigue, sleep difficulties, pain, high alcohol consumption, and anxiety. Predictors of becoming a HUd included substance use, obesity, cardiovascular disease, comorbidity severity, psychiatric conditions other than depression, and pain.

Conclusion: Focusing on pain, substance use, and psychiatric conditions beyond depression may be effective approaches to reducing high costs in patients with depression.
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http://dx.doi.org/10.1016/j.jpsychores.2016.04.002DOI Listing
June 2016

Changes to nitrate isotopic composition of wastewater treatment effluent and rivers after upgrades to tertiary treatment in the Narragansett Bay watershed, RI.

Mar Pollut Bull 2016 Mar 9;104(1-2):61-9. Epub 2016 Feb 9.

University of Rhode Island, Graduate School of Oceanography, South Ferry Road, Narragansett, RI, United States.

Due to nitrogen load reduction policies, wastewater treatment facilities (WWTFs) have upgraded to tertiary treatment - where denitrification reduces and removes nitrogen. Changes to the stable isotopic composition of nitrate inputs after upgrades or how it transfers to the estuary have not been assessed in Rhode Island. We investigate whether these upgrades impact the isotopic signature of nitrate inputs to Narragansett Bay. Samples from rivers and WWTFs discharging to Narragansett Bay characterize the anthropogenic source nitrate (NO3(-)) isotopic composition (δ(15)N-NO3(-) and δ(18)O-NO3(-)) and temporal variability. At one WWTF, tertiary treatment increased effluent nitrate δ(15)N-NO3(-) and δ(18)O-NO3(-) values by ~16‰. Riverine values increased by ~4‰, likely due to the combination of decreases in N and upgrades. Combined river and WWTF flux-weighted isotopic compositions showed enriched values and an amplitude reduction in monthly variability. When seasonal isotopic means are significantly different from other sources, δ(15)N-NO3(-) may be a useful tracer of inputs.
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http://dx.doi.org/10.1016/j.marpolbul.2016.02.010DOI Listing
March 2016

Watching eyes on potential litter can reduce littering: evidence from two field experiments.

PeerJ 2015 1;3:e1443. Epub 2015 Dec 1.

Centre for Behaviour and Evolution, Newcastle University , Newcastle , United Kingdom.

Littering constitutes a major societal problem, and any simple intervention that reduces its prevalence would be widely beneficial. In previous research, we have found that displaying images of watching eyes in the environment makes people less likely to litter. Here, we investigate whether the watching eyes images can be transferred onto the potential items of litter themselves. In two field experiments on a university campus, we created an opportunity to litter by attaching leaflets that either did or did not feature an image of watching eyes to parked bicycles. In both experiments, the watching eyes leaflets were substantially less likely to be littered than control leaflets (odds ratios 0.22-0.32). We also found that people were less likely to litter when there other people in the immediate vicinity than when there were not (odds ratios 0.04-0.25) and, in one experiment but not the other, that eye leaflets only reduced littering when there no other people in the immediate vicinity. We suggest that designing cues of observation into packaging could be a simple but fruitful strategy for reducing littering.
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http://dx.doi.org/10.7717/peerj.1443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671191PMC
December 2015

Accuracy and precision of oscillometric blood pressure in standing conscious horses.

J Vet Emerg Crit Care (San Antonio) 2016 Jan-Feb;26(1):85-92. Epub 2015 Oct 21.

Department of Clinical Sciences, Swedish University of Agricultural Sciences.

Background: Arterial blood pressure (BP) is a relevant clinical parameter that can be measured in standing conscious horses to assess tissue perfusion or pain. However, there are no validated oscillometric noninvasive blood pressure (NIBP) devices for use in horses.

Animals: Seven healthy horses from a teaching and research herd.

Hypothesis/objective: To evaluate the accuracy and precision of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) in conscious horses obtained with an oscillometric NIBP device when compared to invasively measured arterial BP.

Methods: An arterial catheter was placed in the facial or transverse facial artery and connected to a pressure transducer. A cuff for NIBP was placed around the tail base. The BP was recorded during normotension, dobutamine-induced hypertension, and subnormal BP induced by acepromazine administration. Agreement analysis with replicate measures was utilized to calculate bias (accuracy) and standard deviation (SD) of bias (precision).

Results: A total of 252 pairs of invasive arterial BP and NIBP measurements were analyzed. Compared to the direct BP measures, the NIBP MAP had an accuracy of -4 mm Hg and precision of 10 mm Hg. SAP had an accuracy of -8 mm Hg and a precision of 17 mm Hg and DAP had an accuracy of -7 mm Hg and a precision of 14 mm Hg.

Conclusions And Clinical Relevance: MAP from the evaluated NIBP monitor is accurate and precise in the adult horse across a range of BP, with higher variability during subnormal BP. MAP but not SAP or DAP can be used for clinical decision making in the conscious horse.
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http://dx.doi.org/10.1111/vec.12411DOI Listing
September 2016

Physical activity and health in adolescence.

Clin Med (Lond) 2015 Jun;15(3):267-72

Sheffield Teaching Hospitals and Sheffield Hallam University, Sheffield, UK.

Adolescence represents a critical period of development during which personal lifestyle choices and behaviour patterns establish, including the choice to be physically active. Physical inactivity, sedentary behaviour and low cardiorespiratory fitness are strong risk factors for the development of chronic diseases with resulting morbidity and mortality, as well as economic burden to wider society from health and social care provision, and reduced occupational productivity. Worrying trends in adverse physical activity behaviours necessitate urgent and concerted action. Healthcare professionals caring for adolescents and young adults are ideally placed and suited to deliver powerful messages promoting physical activity and behaviour change. Every encounter represents an opportunity to ask about physical activity, provide advice, or signpost to appropriate pathways or opportunities. Key initial targets include getting everyone to reduce their sedentary behaviour and be more active, with even a little being more beneficial than none at all.
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http://dx.doi.org/10.7861/clinmedicine.15-3-267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4953112PMC
June 2015

A CB2-Selective Cannabinoid Suppresses T-Cell Activities and Increases Tregs and IL-10.

J Neuroimmune Pharmacol 2015 Jun 16;10(2):318-32. Epub 2015 May 16.

Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA.

We have previously shown that agonists selective for the cannabinoid receptor 2 (CB2), including O-1966, inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro correlate of organ graft rejection, predominantly through effects on T-cells. Current studies explored the mechanism of this immunosuppression by O-1966 using mouse spleen cells. Treatment with O-1966 dose-relatedly decreased levels of the active nuclear forms of the transcription factors NF-κB and NFAT in wild-type T-cells, but not T-cells from CB2 knockout (CB2R k/o) mice. Additionally, a gene expression profile of purified T-cells from MLR cultures generated using a PCR T-cell activation array showed that O-1966 decreased mRNA expression of CD40 ligand and CyclinD3, and increased mRNA expression of Src-like-adaptor 2 (SLA2), Suppressor of Cytokine Signaling 5 (SOCS5), and IL-10. The increase in IL-10 was confirmed by measuring IL-10 protein levels in MLR culture supernatants. Further, an increase in the percentage of regulatory T-cells (Tregs) was observed in MLR cultures. Pretreatment with anti-IL-10 resulted in a partial reversal of the inhibition of proliferation and blocked the increase of Tregs. Additionally, O-1966 treatment caused a dose-related decrease in the expression of CD4 in MLR cultures from wild-type, but not CB2R k/o, mice. These data support the potential of CB2-selective agonists as useful therapeutic agents to prolong graft survival in transplant patients, and strengthens their potential as a new class of immunosuppressive agents with broader applicability.
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http://dx.doi.org/10.1007/s11481-015-9611-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528965PMC
June 2015