Publications by authors named "Christopher Williams"

850 Publications

A high-throughput HPLC method for simultaneous quantification of pyrethroid and pyriproxyfen in long-lasting insecticide-treated nets.

Sci Rep 2022 Jun 11;12(1):9715. Epub 2022 Jun 11.

Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Pl, Liverpool, L3 5QA, UK.

Long-lasting insecticide-treated nets (LLINs) play a crucial role in preventing malaria transmission. LLINs should remain effective for at least three years, even after repeated washings. Currently, monitoring insecticides in LLINs is cumbersome, costly, and requires specialized equipment and hazardous solvents. Our aim was to develop a simple, high-throughput and low-resource method for measuring insecticides in LLINs. To extract insecticides, polyethylene-LLIN samples were heated at 85 °C for 45 min in a non-hazardous solvent mix containing dicyclohexylphthalate as an internal standard. The extraction solvent was reduced from 50 to 5 ml using a 0.2 g sample, 90% smaller than the recommended sample size. By optimizing HPLC chromatography, we simultaneously detected pyrethroid and pyriproxyfen insecticides with high sensitivity in LLIN's extract. The method can quantify levels ≥ 0.0015% permethrin, 0.00045% alpha-cypermethrin and 0.00025% pyriproxyfen (w/w) in polyethylene, allowing for insecticide tracking before and after the use of LLINs. This method can be used to assess LLINs with 1% pyriproxyfen (pyriproxyfen-LLIN) or 2% permethrin (Olyset® Net), 1% pyriproxyfen and 2% permethrin (Olyset® Duo), or 0.55% pyriproxyfen and 0.55% alpha-cypermethrin (Royal Gaurd®). One can run 120 samples (40 nets) simultaneously with high precision and accuracy, improving throughput and reducing labour, costs, and environmental impact.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-022-13768-zDOI Listing
June 2022

A lesser scaup (Aythya affinis) naturally infected with Eurasian 2.3.4.4 highly pathogenic H5N1 avian influenza virus: Movement ecology and host factors.

Transbound Emerg Dis 2022 Jun 9. Epub 2022 Jun 9.

Department of Entomology and Wildlife Ecology, University of Delaware, Newark, Delaware, USA.

Despite the recognized role of wild waterfowl in the potential dispersal and transmission of highly pathogenic avian influenza (HPAI) virus, little is known about how infection affects these birds. This lack of information limits our ability to estimate viral spread in the event of an HPAI outbreak, thereby limiting our abilities to estimate and communicate risk. Here, we present telemetry data from a wild Lesser Scaup (Aythya affinis), captured during a separate ecology study in the Chesapeake Bay, Maryland. This bird tested positive for infection with clade 2.3.4.4 HPAI virus of the A/goose/Guangdong/1/1996 (Gs/GD) H5N1 lineage (results received post-release) during the 2021-2022 ongoing outbreaks in North America. While the infected bird was somewhat lighter than other adult males surgically implanted with transmitters (790 g, x̅ = 868 g, n = 11), it showed no clinical signs of infection at capture, during surgery, nor upon release. The bird died 3 days later-pathology undetermined as the specimen was not able to be recovered. Analysis of movement data within the 3-day window showed that the infected individual's maximum and average hourly movements (3894.3 and 428.8 m, respectively) were noticeably lower than noninfected conspecifics tagged and released the same day (x̅ = 21,594.5 and 1097.9 m, respectively; n = 4). We identified four instances where the infected bird had close contact (fixes located within 25 m and 15 min) with another marked bird during this time. Collectively, these data suggest that the HPAI-positive bird observed in this study may have been shedding virus for some period prior to death, with opportunities for direct bird-to-bird or environmental transmission. Although limited by low sample size and proximity to the time of tagging, we hope that these data will provide useful information as managers continue to respond to this ongoing outbreak event.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tbed.14614DOI Listing
June 2022

Analytical evaluation of thirty-two severe acute respiratory syndrome 2 lateral flow antigen tests demonstrates sensitivity remains with the SARS-CoV-2 Gamma lineage.

Rev Soc Bras Med Trop 2022 6;55:e0016. Epub 2022 Jun 6.

Liverpool School of Tropical Medicine, Centre for Drugs and Diagnostics, Liverpool, United Kingdom.

Background: The emergence of variants of concern (VOCs) requires an ongoing assessment of the performance of antigen lateral flow tests (Ag-RDTs). The limit of detection (LOD) of 32 Ag-RDTs was evaluated using the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant.

Methods: Ag-RDTs were performed according to the manufacturer's instructions with a clinical isolate of the Gamma variant.

Results: Twenty-eight of the 32 Ag-RDTs exceeded the World Health Organization criteria.

Conclusions: This comprehensive analytical evaluation of Ag-RDTs demonstrated that the test performance was maintained with Gamma VOC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/0037-8682-0016-2022DOI Listing
June 2022

Neuropathologic Findings in Elderly HIV-Positive Individuals.

J Neuropathol Exp Neurol 2022 Jun;81(7):565-576

Section of Neuropathology, Department of Pathology and Laboratory Medicine, Ronald Reagan UCLA Medical Center and David Geffen School of Medicine, Los Angeles, CA, USA.

The elderly HIV-positive population is growing due to the widespread use of combination antiretroviral therapy (cART), but the effects of longstanding HIV infection on brain aging are unknown. A significant proportion of HIV-positive individuals develop HIV-associated neurocognitive disorder (HAND) even on cART, but the pathogenesis of HAND is unknown. Although neuroinflammation is postulated to play an important role in aging and neurodegenerative diseases such as Alzheimer disease (AD), it is unclear whether HIV accelerates aging or increases the risk for AD. We examined the brains of 9 elderly HIV-positive subjects on cART without co-infection by hepatitis C virus compared to 7 elderly HIV-negative subjects. Microglial and astrocyte activation and AD pathologic change in association with systemic comorbidities and neurocognitive assessment were evaluated. There was no difference in microglial or astrocyte activation between our HIV-positive and HIV-negative cohorts. One HIV-positive subject and 2 HIV-negative subjects demonstrated significant amyloid deposition, predominantly in the form of diffuse senile plaques, but these individuals were cognitively normal. Neurofibrillary tangles were sparse in the HIV-positive cohort. There was a high prevalence of cardiovascular comorbidities in all subjects. These findings suggest that multiple factors likely contribute to aging and cognitive impairment in elderly HIV-positive individuals on cART.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnen/nlac040DOI Listing
June 2022

Stereotactic Magnetic Resonance Guided Adaptive Radiation Therapy (SMART) for Abdominopelvic Oligometastases.

Int J Radiat Oncol Biol Phys 2022 May 19. Epub 2022 May 19.

Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:

Purpose: Stereotactic body radiation therapy can be an effective treatment for oligometastases. However, safe delivery of ablative radiation is frequently limited by the proximity of mobile organs sensitive to high radiation doses. The goal of this study is to determine the feasibility, safety, and disease control outcomes of stereotactic magnetic resonance guided adaptive radiation therapy (SMART) in patients with abdominopelvic oligometastases.

Methods And Materials: We identified 101 patients with abdominopelvic oligometastases, including 20 patients enrolled on phase 1 protocols, who were consecutively treated with SMART on a 0.35T MR linac at a single institution from October 2019 to September 2021. Local control and overall survival were analyzed using the Kaplan-Meier method.

Results: Overall, 114 tumors were treated. The most common histology was prostate adenocarcinoma (53.5%, n=60), and 57.0% (n=65) of sites were centered in the pelvis. 79.8% of sites (n=91) were treated to 8 Gy × 5, and 43.0% (n=49) were treated with breath hold respiratory gating. Online adaptation resulted in a clinically significant improvement in coverage or organ sparing in 86.6% of delivered fractions. The median time required for adaptation was 24 minutes, and the median time in the treatment room was 58 minutes. With median follow-up of 11.4 months, the 12-month local control was 93% and higher for prostate adenocarcinoma vs other histologies (100% vs 84%, P=0.009). The 12-month overall survival was 96% and higher for prostate adenocarcinoma vs other histologies (100% vs 91%, P=0.046). Three patients (3.0%) developed grade 3 toxicities (colonic hemorrhage at 3.4 months and urinary tract obstructions at 10.1 and 18.4 months).

Conclusions: SMART is feasible, safe, and effective for delivering ablative radiotherapy to abdominopelvic metastases. Adaptive planning was necessary in the large majority of cases. The advantages of SMART warrant its further investigation as a standard option for the treatment of abdominopelvic oligometastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2022.05.016DOI Listing
May 2022

Stereotactic Magnetic Resonance Guided Adaptive Radiation Therapy (SMART) for Abdominopelvic Oligometastases.

Int J Radiat Oncol Biol Phys 2022 May 19. Epub 2022 May 19.

Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:

Purpose: Stereotactic body radiation therapy can be an effective treatment for oligometastases. However, safe delivery of ablative radiation is frequently limited by the proximity of mobile organs sensitive to high radiation doses. The goal of this study is to determine the feasibility, safety, and disease control outcomes of stereotactic magnetic resonance guided adaptive radiation therapy (SMART) in patients with abdominopelvic oligometastases.

Methods And Materials: We identified 101 patients with abdominopelvic oligometastases, including 20 patients enrolled on phase 1 protocols, who were consecutively treated with SMART on a 0.35T MR linac at a single institution from October 2019 to September 2021. Local control and overall survival were analyzed using the Kaplan-Meier method.

Results: Overall, 114 tumors were treated. The most common histology was prostate adenocarcinoma (53.5%, n=60), and 57.0% (n=65) of sites were centered in the pelvis. 79.8% of sites (n=91) were treated to 8 Gy × 5, and 43.0% (n=49) were treated with breath hold respiratory gating. Online adaptation resulted in a clinically significant improvement in coverage or organ sparing in 86.6% of delivered fractions. The median time required for adaptation was 24 minutes, and the median time in the treatment room was 58 minutes. With median follow-up of 11.4 months, the 12-month local control was 93% and higher for prostate adenocarcinoma vs other histologies (100% vs 84%, P=0.009). The 12-month overall survival was 96% and higher for prostate adenocarcinoma vs other histologies (100% vs 91%, P=0.046). Three patients (3.0%) developed grade 3 toxicities (colonic hemorrhage at 3.4 months and urinary tract obstructions at 10.1 and 18.4 months).

Conclusions: SMART is feasible, safe, and effective for delivering ablative radiotherapy to abdominopelvic metastases. Adaptive planning was necessary in the large majority of cases. The advantages of SMART warrant its further investigation as a standard option for the treatment of abdominopelvic oligometastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2022.05.016DOI Listing
May 2022

Role of HER2 in Prognosis of Salivary Duct Carcinoma: A Systematic Review and Meta-Analysis.

Laryngoscope 2022 May 14. Epub 2022 May 14.

Department of Otolaryngology, Head and Neck Surgery, Southern Illinois University, Springfield, Illinois, U.S.A.

Objectives: Salivary duct carcinoma (SDC) is a rare, aggressive malignancy with a poor prognosis. These tumors frequently stain positive for HER2/ErbB2, but data on the prognostic significance of HER2 status in SDC are mixed. We sought to determine whether HER2 status affects survival outcomes in SDC.

Methods: PubMed, Embase, and Web of Science databases were searched from inception to October 2020. Eligibility was restricted to studies reporting HER2/ErbB2 overexpression in histologically confirmed de novo SDC or SDC ex pleomorphic adenoma, with corresponding overall (OS) and disease-free (DFS) survival measures. Separate multivariable and univariable meta-analyses were performed using random-effects models. Statistical heterogeneity was estimated by Cochran's Q and I tests. Funnel plots were generated and Egger's test was used to assess for publication bias. The risk of bias was assessed with the Newcastle-Ottawa Scale.

Results: Of 183 unique citations, 14 studies of 663 patients were included. Most included studies determined HER2 status according to ASCO/CAP guidelines. The univariable meta-analysis did not reveal an effect between HER2 status and OS (HR 1.09, 95% CI 0.84-1.42). In the multivariable analysis, HER2 positivity was associated with a HR of 1.49 for OS (95% CI 0.96-2.30). Fewer studies reported data for DFS than OS, with no relationship between HER2 status and DFS found on multivariable or univariable meta-analyses.

Conclusion: In patients with salivary duct carcinoma, HER2 positivity was not found to be associated with worse overall survival. This information may be useful when counseling patients and considering treatment options. Laryngoscope, 2022.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.30214DOI Listing
May 2022

3D Printing Carbonaceous Objects from Polyimide Pyrolysis.

ACS Macro Lett 2021 04 17;10(4):412-418. Epub 2021 Mar 17.

Arizona State University, School of Molecular Science and Biodesign Center for Sustainable Macromolecular Materials and Manufacturing, Tempe, Arizona 85281, United States.

Fully aromatic polyimides are amenable to efficient carbonization in thin two-dimensional (2D) films due to a complement of aromaticity and planarity of backbone repeating units. However, repeating unit rigidity traditionally imposes processing limitations, restricting many fully aromatic polyimides, e.g., pyromellitic dianhydride with 4,4'-oxidianiline (PMDA-ODA) polyimides, to a 2D form factor. Recently, research efforts in our laboratories enabled additive manufacturing of micron-scale resolution PMDA-ODA polyimide objects using vat photopolymerization (VP) and ultraviolet-assisted direct ink write (UV-DIW) following careful thermal postprocessing of the three-dimensional (3D) organogel precursors to 400 °C. Further thermal postprocessing of printed objects to 1000 °C induced pyrolysis of the PMDA-ODA objects to disordered carbon. The pyrolyzed objects retained excellent geometric resolution, and Raman spectroscopy displayed characteristic disordered (D) and graphitic (G) carbon bands. Scanning electron microscopy probed the cross-sectional homogeneity of the carbonized samples, revealing an absence of pore formation during carbonization. Likewise, impedance analysis of carbonized specimens indicated only a moderate decrease in conductivity compared to thin films that were pyrolyzed using an identical carbonization process. Facile pyrolysis of PMDA-ODA objects now enables the production of carbonaceous monoliths with complex and predictable three-dimensional geometries using commercially available starting materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsmacrolett.1c00032DOI Listing
April 2021

A Competency-Guided Approach to Optimizing a Physician-Scientist Curriculum.

Med Sci Educ 2022 Apr 7;32(2):523-528. Epub 2022 Mar 7.

Medical Scientist Training Program, Office of Health Science Education, Room 222 Eskind Biomedical Library and Learning Center, 2209 Garland Avenue, Nashville, TN 37240 USA.

Physician-scientists are uniquely positioned to achieve significant biomedical advances to improve the human condition. Their clinical and scientific training allows them to bridge fields and contribute to cutting-edge, clinically relevant research. The need for a highly skilled physician-scientist workforce has never been more acute. We propose a competency-guided program design (CGPD) framework that focuses on core skills to enhance the physician-scientist training curriculum. In partnership with clinical and graduate curricula, the CGPD framework can be employed as a tool to meaningfully integrate physician-scientist training, address barriers to attract and sustain the physician-scientist workforce, and avoid overprogramming that detracts from a solid foundation of clinical and graduate research training.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40670-022-01525-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9054991PMC
April 2022

MTG16 regulates colonic epithelial differentiation, colitis, and tumorigenesis by repressing E protein transcription factors.

JCI Insight 2022 May 23;7(10). Epub 2022 May 23.

Program in Cancer Biology and.

Aberrant epithelial differentiation and regeneration contribute to colon pathologies, including inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Myeloid translocation gene 16 (MTG16, also known as CBFA2T3) is a transcriptional corepressor expressed in the colonic epithelium. MTG16 deficiency in mice exacerbates colitis and increases tumor burden in CAC, though the underlying mechanisms remain unclear. Here, we identified MTG16 as a central mediator of epithelial differentiation, promoting goblet and restraining enteroendocrine cell development in homeostasis and enabling regeneration following dextran sulfate sodium-induced (DSS-induced) colitis. Transcriptomic analyses implicated increased Ephrussi box-binding transcription factor (E protein) activity in MTG16-deficient colon crypts. Using a mouse model with a point mutation that attenuates MTG16:E protein interactions (Mtg16P209T), we showed that MTG16 exerts control over colonic epithelial differentiation and regeneration by repressing E protein-mediated transcription. Mimicking murine colitis, MTG16 expression was increased in biopsies from patients with active IBD compared with unaffected controls. Finally, uncoupling MTG16:E protein interactions partially phenocopied the enhanced tumorigenicity of Mtg16-/- colon in the azoxymethane/DSS-induced model of CAC, indicating that MTG16 protects from tumorigenesis through additional mechanisms. Collectively, our results demonstrate that MTG16, via its repression of E protein targets, is a key regulator of cell fate decisions during colon homeostasis, colitis, and cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.153045DOI Listing
May 2022

A pyrosequencing protocol for rapid identification of SARS-CoV-2 variants.

J Med Virol 2022 Aug 21;94(8):3661-3668. Epub 2022 Apr 21.

Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

Next-generation sequencing (NGS) is the primary method used to monitor the distribution and emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants around the world; however, it is costly and time-consuming to perform and is not widely available in low-resourced geographical regions. Pyrosequencing has the potential to augment surveillance efforts by providing information on specific targeted mutations for rapid identification of circulating and emerging variants. The current study describes the development of a reverse transcription (RT)-PCR-pyrosequencing assay targeting >65 spike protein gene (S) mutations of SARS-CoV-2, which permits differentiation of commonly reported variants currently circulating in the United States with a high degree of confidence. Variants typed using the assay included B.1.1.7 (Alpha), B.1.1.529 (Omicron), B.1.351 (Beta), B.1.375, B.1.427/429 (Epsilon), B.1.525 (Eta), B.1.526.1 (Iota), B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.621 (Mu), P1 (Gamma), and B.1.1 variants, all of which were confirmed by the NGS data. An electronic typing tool was developed to aid in the identification of variants based on mutations detected by pyrosequencing. The assay could provide an important typing tool for rapid identification of candidate patients for monoclonal antibody therapies and a method to supplement SARS-CoV-2 surveillance efforts by identification of circulating variants and novel emerging lineages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.27770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088475PMC
August 2022

Subchondral versus intra-articular orthobiologic injections for the treatment of knee osteoarthritis: a review.

Regen Med 2022 06 12;17(6):389-400. Epub 2022 Apr 12.

Department of Orthopaedics, Emory University, Atlanta, GA 30322, USA.

Recent perspectives suggest that osteoarthritis (OA) is a disease involving not only the articular cartilage but also the osteochondral unit, including the synovium, supportive cartilage and subchondral bone. Current conservative treatments for OA are symptomatic and do not prevent progression or reverse the disease process. Compelling data show that intra-articular orthobiologic injections, such as platelet-rich plasma and mesenchymal stromal cells, are effective in providing relief of OA symptoms. However, recent data suggest that injections of orthobiologics into the subchondral bone may be superior to intra-articular injections for the management of OA. This review highlights the rationale and current evidence for intra-articular and subchondral bone injections of orthobiologics for the treatment of OA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/rme-2021-0174DOI Listing
June 2022

Piperacillin/tazobactam-resistant, cephalosporin-susceptible bloodstream infections are driven by multiple acquisition of resistance across diverse sequence types.

Microb Genom 2022 04;8(4)

Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.

Resistance to piperacillin/tazobactam (TZP) in has predominantly been associated with mechanisms that confer resistance to third-generation cephalosporins. Recent reports have identified strains with phenotypic resistance to piperacillin/tazobactam but susceptibility to third-generation cephalosporins (TZP-R/3GC-S). In this study we sought to determine the genetic diversity of this phenotype in (=58) isolated between 2014-2017 at a single tertiary hospital in Liverpool, UK, as well as the associated resistance mechanisms. We compare our findings to a UK-wide collection of invasive isolates (=1509) with publicly available phenotypic and genotypic data. These data sets included the TZP-R/3GC-S phenotype (=68), and piperacillin/tazobactam and third-generation cephalosporin-susceptible (TZP-S/3GC-S, =1271) phenotypes. The TZP-R/3GC-S phenotype was displayed in a broad range of sequence types, which was mirrored in the same phenotype from the UK-wide collection, and the overall diversity of invasive isolates. The TZP-R/3GC-S isolates contained a diverse range of plasmids, indicating multiple acquisition events of TZP resistance mechanisms rather than clonal expansion of a particular plasmid or sequence type. The putative resistance mechanisms were equally diverse, including hyperproduction of TEM-1, either via strong promoters or gene amplification, carriage of inhibitor-resistant β-lactamases, and an S133G mutation detected for the first time in clinical isolates. Several of these mechanisms were present at a lower abundance in the TZP-S/3GC-S isolates from the UK-wide collection, but without the associated phenotypic resistance to TZP. Eleven (19%) of the isolates had no putative mechanism identified from the genomic data. Our findings highlight the complexity of this cryptic phenotype and the need for continued phenotypic monitoring, as well as further investigation to improve detection and prediction of the TZP-R/3GC-S phenotype from genomic data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1099/mgen.0.000789DOI Listing
April 2022

Understanding unidentified human remains investigations through the United States census data.

Forensic Sci Int Synerg 2022 28;4:100225. Epub 2022 Mar 28.

RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709, USA.

Each year, thousands of unidentified human remains (UHR) cases are reported in the U.S. Technological advances have greatly enhanced the forensic community's capacity and capability to solve UHR cases, but little is known about the extent to which these resources are used by medical examiners and coroners (MECs). Using public datasets, the study purpose is to describe the current state MEC system with respect to UHR cases, the resources used to investigate these cases, and the evidence retention polices in place. There was an overall decline in UHR cases reported between 2004 and 2018. Less than half of MECs in both study years reported having established written final disposition and evidence retention policies for UHR cases. National missing persons databases were underused. This study provides an important window into the present state of UHRs being handled by our Nation's MEC offices and the resources available to solve these difficult cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsisyn.2022.100225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968461PMC
March 2022

Pearls of wisdom for aspiring physician-scientist residency applicants and program directors.

JCI Insight 2022 03 22;7(6). Epub 2022 Mar 22.

Department of Medicine, Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Veterans Affairs Tennessee Valley Health Care System, Nashville, Tennessee, USA; Vanderbilt Ingram Cancer Center, Nashville, Tennessee, USA.

Postgraduate physician-scientist training programs (PSTPs) enhance the experiences of physician-scientist trainees following medical school graduation. PSTPs usually span residency and fellowship training, but this varies widely by institution. Applicant competitiveness for these programs would be enhanced, and unnecessary trainee anxiety relieved, by a clear understanding of what factors define a successful PSTP matriculant. Such information would also be invaluable to PSTP directors and would allow benchmarking of their admissions processes with peer programs. We conducted a survey of PSTP directors across the US to understand the importance they placed on components of PSTP applications. Of 41 survey respondents, most were from internal medicine and pediatrics residency programs. Of all components in the application, two elements were considered very important by a majority of PSTP directors: (a) having one or more first-author publications and (b) the thesis advisor's letter. Less weight was consistently placed on factors often considered more relevant for non-physician-scientist postgraduate applicants - such as US Medical Licensing Examination scores, awards, and leadership activities. The data presented here highlight important metrics for PSTP applicants and directors and suggest that indicators of scientific productivity and commitment to research outweigh traditional quantitative measures of medical school performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.158467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986063PMC
March 2022

Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis.

Int J Mol Sci 2022 Mar 7;23(5). Epub 2022 Mar 7.

Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 1415 S. Martin L. King Jr. Blvd., Tallahassee, FL 32307, USA.

Aromatase inhibitors (AIs) are standard treatment for estrogen-dependent postmenopausal breast tumors; however, resistance develops leading to tumor relapse and metastasis. We previously demonstrated that glyceollin inhibits proliferation, survival, and migration of hormone-independent letrozole-resistant breast cancer. Since many AI-resistant tumors remain hormone-dependent, identifying distinctions between estrogen-receptor-positive (ER+) and ER-negative (ER-) AI-resistant tumor response to therapy is critical. We hypothesize that treating ER+ letrozole-resistant T47D breast cancer cells (T47DaromLR) with a combination of 10 μM glyceollin and 0.5 μM lapatinib (a dual EGFR/HER2 inhibitor) will decrease cell proliferation through induction of apoptosis. The T47DaromLR cells were found to overexpress HER2 and MAPK while maintaining aromatase and ER levels compared to their letrozole-sensitive (T47Darom) counterparts. In the absence of estrogen stimulation, glyceollin ± lapatinib had no effect on the proliferation of the T47Darom cells, while glyceollin treatment caused 46% reduction in the proliferation of T47DaromLR cells, which was further diminished when combined with lapatinib. While neither agent influenced cell migration, glyceollin and lapatinib reduced S and G2/M phase cell entry and exclusively induced apoptosis by 1.29-fold in the T47DaromLR cells. Taken together, these results suggest that glyceollins and lapatinib may have potential as a novel combination therapeutic approach for hormone-dependent, letrozole-resistant tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms23052887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911299PMC
March 2022

COVID-19 vaccine uptake and effectiveness in adults aged 50 years and older in Wales UK: a 1.2m population data-linkage cohort approach.

Hum Vaccin Immunother 2022 12 3;18(1):2031774. Epub 2022 Mar 3.

Population Data Science, Health Data Research UK, Swansea University Medical School, Swansea, UK.

Vaccination programs against COVID-19 vary globally with estimates of vaccine effectiveness (VE) affected by vaccine type, schedule, strain, outcome, and recipient characteristics. This study assessed VE of BNT162b2 and ChAdOx1 vaccines against PCR positive SARS-CoV-2 infection, hospital admission, and death among adults aged 50 years and older in Wales, UK during the period 7 December 2020 to 18 July 2021, when Alpha, followed by Delta, were the predominant variants. We used individual-level linked routinely collected data within the Secure Anonymized Information Linkage (SAIL) Databank. Data were available for 1,262,689 adults aged 50 years and over; coverage of one dose of any COVID-19 vaccine in this population was 92.6%, with coverage of two doses 90.4%. VE against PCR positive infection at 28-days or more post first dose of any COVID-19 vaccine was 16.0% (95%CI 9.6-22.0), and 42.0% (95%CI 36.5-47.1) seven or more days after a second dose. VE against hospital admission was higher at 72.9% (95%CI 63.6-79.8) 28 days or more post vaccination with one dose of any vaccine type, and 84.9% (95%CI 78.2-89.5) at 7 or more days post two doses. VE for one dose against death was estimated to be 80.9% (95%CI 72.1-86.9). VE against PCR positive infection and hospital admission was higher for BNT162b2 compared to ChAdOx1. In conclusion, vaccine uptake has been high among adults in Wales and VE estimates are encouraging, with two doses providing considerable protection against severe outcomes. Continued roll-out of the vaccination programme within Wales, and globally, is crucial in our fight against COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21645515.2022.2031774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993055PMC
December 2022

SARS-CoV-2 enzyme-linked immunosorbent assays as proxies for plaque reduction neutralisation tests.

Sci Rep 2022 03 1;12(1):3351. Epub 2022 Mar 1.

Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Liverpool, UK.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread globally since its emergence in 2019. Most SARS-CoV-2 infections generate immune responses leading to rising levels of immunoglobulins (Ig) M, A and G which can be detected using diagnostic tests including enzyme-linked immunosorbent assays (ELISA). Whilst implying previous SARS-CoV-2 infection, the detection of Ig by ELISA does not guarantee the presence of neutralising antibodies (NAb) that can prevent the virus infecting cells. Plaque reduction neutralisation tests (PRNT) detect NAb, but are not amenable to mass testing as they take several days and require use of SARS-CoV-2 in high biocontainment laboratories. We evaluated the ability of IgG and IgM ELISAs targeting SARS-CoV-2 spike subunit 1 receptor binding domain (S1-RBD), and spike subunit 2 (S2) and nucleocapsid protein (NP), at predicting the presence and magnitude of NAb determined by PRNT. IgG S2 + NP ELISA was 96.8% [95% CI 83.8-99.9] sensitive and 88.9% [95% CI 51.8-99.7] specific at predicting the presence of NAbs (PRNT > 1:40). IgG and IgM S1-RBD ELISAs correlated with PRNT titre, with higher ELISA results increasing the likelihood of a robust neutralising response. The IgM S1-RBD assay can be used as a rapid, high throughput test to approximate the magnitude of NAb titre.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-022-07263-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888744PMC
March 2022

Low back pain presentations to rural, regional, and metropolitan emergency departments.

Aust J Rural Health 2022 Mar 1. Epub 2022 Mar 1.

School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.

Objective: To describe the context of low back pain (LBP) presentations to emergency departments (EDs) by remoteness areas, hospital delineation level and staffing portfolios.

Design: A retrospective observational study using routinely captured ED and admission data over a 5-year period (July 2014-June 2019).

Settings: Thirty seven EDs across a large health district in NSW, Australia, covering major cities, inner regional areas and outer regional areas.

Participants: Emergency department (ED) presentations with a principal or secondary diagnosis of LBP based on ICD-10 code (M54.5).

Main Outcome Measures: ED presentation and associated admission measures, including presentation rate, referral source, time in ED, re-presentation rate, admission details and cost to the health system.

Results: There were 26 509 ED presentations for LBP across the 5 years. Time spent in ED was 206 min for EDs in major cities, 146 min for inner regional EDs and 89 min for outer regional EDs. Re-presentation rates were 6% in major cities, 8.8% in inner regional EDs and 11.8% in outer regional EDs. Admission rates were 20.4%, 15.8% and 18.8%, respectively.

Conclusions: This study describes LBP presentations across 37 EDs, highlighting the potential burden these presentations place on hospitals. LBP presentations appear to follow different pathways depending on the ED remoteness area, delineation level and staff portfolio.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajr.12854DOI Listing
March 2022

Fluoroscopic 3D Image Generation from Patient-Specific PCA Motion Models Derived from 4D-CBCT Patient Datasets: A Feasibility Study.

J Imaging 2022 Jan 18;8(2). Epub 2022 Jan 18.

Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

A method for generating fluoroscopic (time-varying) volumetric images using patient-specific motion models derived from four-dimensional cone-beam CT (4D-CBCT) images was developed. 4D-CBCT images acquired immediately prior to treatment have the potential to accurately represent patient anatomy and respiration during treatment. Fluoroscopic 3D image estimation is performed in two steps: (1) deriving motion models and (2) optimization. To derive motion models, every phase in a 4D-CBCT set is registered to a reference phase chosen from the same set using deformable image registration (DIR). Principal components analysis (PCA) is used to reduce the dimensionality of the displacement vector fields (DVFs) resulting from DIR into a few vectors representing organ motion found in the DVFs. The PCA motion models are optimized iteratively by comparing a cone-beam CT (CBCT) projection to a simulated projection computed from both the motion model and a reference 4D-CBCT phase, resulting in a sequence of fluoroscopic 3D images. Patient datasets were used to evaluate the method by estimating the tumor location in the generated images compared to manually defined ground truth positions. Experimental results showed that the average tumor mean absolute error (MAE) along the superior-inferior (SI) direction and the 95th percentile in two patient datasets were 2.29 and 5.79 mm for patient 1, and 1.89 and 4.82 mm for patient 2. This study demonstrated the feasibility of deriving 4D-CBCT-based PCA motion models that have the potential to account for the 3D non-rigid patient motion and localize tumors and other patient anatomical structures on the day of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jimaging8020017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879782PMC
January 2022

Online Cognitive Behavioral Therapy (CBT) Life Skills Program for Depression: Pilot Randomized Controlled Trial.

JMIR Form Res 2022 Feb 17;6(2):e30489. Epub 2022 Feb 17.

Sir Henry Wellcome Building for Mood Disorders Research, University of Exeter, Exeter, United Kingdom.

Background: Depression is a common mental health problem with significant personal and social consequences. Studies have suggested that cognitive behavioral therapy (CBT) is an effective treatment for depression and anxiety when delivered one-to-one by an expert practitioner, but access to this talking therapy is often limited, and waiting lists can be long. However, a range of low-intensity interventions that can increase access to services are available including guided CBT self-help materials delivered via books, classes, and online packages.

Objective: This project aimed to pilot a randomized controlled trial (RCT) of an online CBT-based life skills course with community-based individuals experiencing depression.

Methods: Individuals with symptoms of depression were recruited directly from the community via newspaper advertisements. Participants were remotely randomized to receive either immediate access (IA) or delayed access (DA) to a research version of the Living Life to the Full online CBT-based life skills package (3rd edition) with telephone support provided by nonspecialist, charity-based workers while they used the online intervention. The primary end point was at 3 months postrandomization, at which point, the DA group were offered the intervention. Levels of depression, anxiety, social functioning, and satisfaction were assessed.

Results: There were effective recruitment, randomization, and uptake, with 19 IA and 17 DA control participants entering the pilot study via newspaper advertisements and 13 of the 19 participants taking up the intervention. Overall, 72% (26/36) were not currently under the care of their general practitioner. The online package was acceptable to participants; the mean satisfaction score on the Client Satisfaction Questionnaire was 21 out of 32 (SD 8.89). At 3 months, data collection was achieved from 78% (28/36) of the participants. The efficacy and retention data were used for a power calculation indicating that 72 participants in total will be required for a future substantive RCT.

Conclusions: The research design successfully tested the recruitment, data collection, and intervention delivery. The pilot study has provided data for the required sample size for the full RCT.

Trial Registration: ISRCTN registry ISRCTN12890709; https://doi.org/10.1186/ISRCTN12890709.

International Registered Report Identifier (irrid): RR2-10.1186/s13063-016-1336-y.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/30489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895278PMC
February 2022

A molecular simulation study into the stability of hydrated graphene nanochannels used in nanofluidics devices.

Nanoscale 2022 Mar 7;14(9):3467-3479. Epub 2022 Mar 7.

Department of Chemical Engineering and Analytical Science, School of Engineering, The University of Manchester, Manchester, UK.

Graphene-based nanochannels are a popular choice in emerging nanofluidics applications because of their tunable and nanometer-scale channels. In this work, molecular dynamics (MD) simulations were employed both to (i) assess the stability of dry and hydrated graphene nanochannels and (ii) elucidate the properties of water confined in these channels, using replica-scale models with 0.66-2.38 nm channel heights. The use of flexible nanochannel walls allows the nanochannel height to relax in response to the solvation forces arising from the confined fluid and the forces between the confining surfaces, without the need for application of arbitrarily high external pressures. Dry nanochannels were found to completely collapse if the initial nanochannel height was less than 2 nm, due to attractive van der Waals interactions between the confining graphene surfaces. However, the presence of water was found to prevent total nanochannel collapse, due to repulsive hydration forces opposing the attractive van der Waals force. For nanochannel heights less than ∼1.7 nm, the confining surfaces must be relaxed to obtain accurate hydration pressures and water diffusion coefficients, by ensuring commensurability between the number of confined water layers and the channel height. For very small (∼0.7 nm), hydrated channels a pressure of 231 MPa due to the van der Waals forces was obtained. In the same system, the confined water forms a mobile, liquid monolayer with a diffusion coefficient of 4.0 × 10 cm s, much higher than bulk liquid water. Although this finding conflicts with most classical MD simulations, which predict in-plane order and arrested dynamics, it is supported by experiments and recently published first-principles MD simulations. Classical simulations can therefore be used to predict the properties of water confined in sub-nanometre graphene channels, providing sufficiently realistic molecular models and accurate intermolecular potentials are employed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1nr08275bDOI Listing
March 2022

Streptococcus pneumoniae colonization associates with impaired adaptive immune responses against SARS-CoV-2.

J Clin Invest 2022 04;132(7)

Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

BackgroundAlthough recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, cases of coinfection with Streptococcus pneumoniae in patients with coronavirus disease 2019 (COVID-19) during hospitalization have been reported infrequently. This apparent contradiction may be explained by interactions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pneumococci in the upper airway, resulting in the escape of SARS-CoV-2 from protective host immune responses.MethodsHere, we investigated the relationship of these 2 respiratory pathogens in 2 distinct cohorts of health care workers with asymptomatic or mildly symptomatic SARS-CoV-2 infection identified by systematic screening and patients with moderate to severe disease who presented to the hospital. We assessed the effect of coinfection on host antibody, cellular, and inflammatory responses to the virus.ResultsIn both cohorts, pneumococcal colonization was associated with diminished antiviral immune responses, which primarily affected mucosal IgA levels among individuals with mild or asymptomatic infection and cellular memory responses in infected patients.ConclusionOur findings suggest that S. pneumoniae impair host immunity to SARS-CoV-2 and raise the question of whether pneumococcal carriage also enables immune escape of other respiratory viruses and facilitates reinfection.Trial registrationISRCTN89159899 (FASTER study) and ClinicalTrials.gov NCT03502291 (LAIV study).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI157124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970672PMC
April 2022

Technical note: Toward implementation of MR-guided radiation therapy for laryngeal cancer with healthy volunteer imaging and a custom MR-CT larynx phantom.

Med Phys 2022 Mar 4;49(3):1814-1821. Epub 2022 Feb 4.

Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Purpose: Internal motion of the larynx can cause normal tissue toxicity and/or tumor underdosage during radiotherapy. MR-guided radiation therapy (MRgRT) provides improved soft-tissue contrast for patient setup and real-time gating of radiation based on cine imaging of tumor motion, potentially making it an advantageous modality for laryngeal treatments. However, there are potential concerns regarding the small target size, proximity to heterogeneous tissue interfaces in the airway that may cause dosimetric errors in the presence of the magnetic field, and uncertainty about the ability of MR-linear accelerator (MR-Linac) systems to visualize and track laryngeal motion. To date, there have been no reports of the use of MRgRT for laryngeal treatments.

Methods: A healthy volunteer was imaged on a ViewRay MRIdian MR-Linac. Organs-at-risk and a laryngeal pseudo target were contoured and used to generate a stereotactic body radiotherapy plan. A custom phantom was created using 3D-printing based on structures delineated on the volunteer images to construct an enclosure containing the target and airway anatomy, with a gap for radiochromic film, and filled with gelatin . The treatment plan was mapped onto the phantom and delivered dose assessed on radiochromic film with global normalization and a 10% dose threshold. A cine MR of the volunteer was acquired to assess the magnitude of larynx motion with speaking and swallowing, and system's ability to gate radiation.

Results: A clinically acceptable laryngeal treatment plan and larynx phantom that was MR and computed tomography-visible were successfully created. The delivered dose had good agreement with the treatment plan with a gamma passing rate of 96.5% (3%/2 mm). The MR-Linac was able to visualize, track, and gate larynx motion.

Conclusions: The MRgRT workflow for laryngeal treatments was assessed and performed in preparation for clinical implementation on the MR-Linac, demonstrating that it is feasible to treat laryngeal cancer patients on the MR-Linac.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mp.15472DOI Listing
March 2022

Moderated Basicity of Endohedral Amine Groups in an Octa-Cationic Self-Assembled Cage.

Angew Chem Int Ed Engl 2022 03 27;61(11):e202117011. Epub 2022 Jan 27.

Department of Chemistry and the UCR Center for Catalysis, University of California-Riverside, Riverside, CA, 92521, USA.

A self-assembled Fe L cage was synthesized with 12 internal amines in the cavity. The cage forms as the dodeca-ammonium salt, despite the cage carrying an overall 8+ charge at the metal centers, extracting protons from displaced water in the reaction. Despite this, the basicity of the internal amines is lower than their counterparts in free solution. The 12 amines have a sliding scale of basicity, with a ≈6 pK unit difference between the first and last protons to be removed. This moderation of side-chain basicity in an active site is a hallmark of enzymatic catalysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202117011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885886PMC
March 2022

Epigenetic Regulation of Associates With Myocardial Infarction and Platelet Function.

Circ Res 2022 02 11;130(3):384-400. Epub 2022 Jan 11.

MRC Integrative Epidemiology Unit at University of Bristol, United Kingdom (L.J.C., L.F., A.G., L.P., M.R.M., C.R., J.L.M., G.D.S., N.J.T.).

Background: DNA hypomethylation at the (F2R like thrombin or trypsin receptor 3) locus has been associated with both smoking and atherosclerotic cardiovascular disease; whether these smoking-related associations form a pathway to disease is unknown. encodes protease-activated receptor 4, a potent thrombin receptor expressed on platelets. Given the role of thrombin in platelet activation and the role of thrombus formation in myocardial infarction, alterations to this biological pathway could be important for ischemic cardiovascular disease.

Methods: We conducted multiple independent experiments to assess whether DNA hypomethylation at in response to smoking is associated with risk of myocardial infarction via changes to platelet reactivity. Using cohort data (N=3205), we explored the relationship between smoking, DNA hypomethylation at , and myocardial infarction. We compared platelet reactivity in individuals with low versus high DNA methylation at (N=41). We used an in vitro model to explore the biological response of to cigarette smoke extract. Finally, a series of reporter constructs were used to investigate how differential methylation could impact gene expression.

Results: Observationally, DNA methylation at mediated an estimated 34% of the smoking effect on increased risk of myocardial infarction. An association between methylation group (low/high) and platelet reactivity was observed in response to PAR4 (protease-activated receptor 4) stimulation. In cells, cigarette smoke extract exposure was associated with a 4.9% to 9.3% reduction in DNA methylation at and a corresponding 1.7-(95% CI, 1.2-2.4, =0.04) fold increase in mRNA. Results from reporter assays suggest the exon 2 region of may help control gene expression.

Conclusions: Smoking-induced epigenetic DNA hypomethylation at appears to increase PAR4 expression with potential downstream consequences for platelet reactivity. Combined evidence here not only identifies DNA methylation as a possible contributory pathway from smoking to cardiovascular disease risk but from any feature potentially influencing regulation in a similar manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCRESAHA.121.318836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812435PMC
February 2022

Are you happier if you reap what you sow? A commentary on compensation and morale among current reproductive endocrinology and infertility specialists.

Fertil Steril 2022 02 31;117(2):431-432. Epub 2021 Dec 31.

Division of Reproductive Endocrinology and Infertility, University of Virginia, Virginia Fertility and IVF, Charlottesville, Virginia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2021.11.036DOI Listing
February 2022

Compliance with telephone-based lifestyle weight loss programs improves low back pain but not knee pain outcomes: complier average causal effects analyses of 2 randomised trials.

Pain 2022 Jul 12;163(7):e862-e868. Epub 2021 Oct 12.

School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.

Abstract: We conducted a complier average causal effect (CACE) analyses for 2 pragmatic randomised controlled trials. We aimed to assess the effectiveness of telephone-based lifestyle weight loss interventions compared with usual care among compliers. Participants from 2 trials with low back pain (n = 160) and knee osteoarthritis (n = 120) with a body mass index ≥27 kg/m2 were included. We defined adherence to the telephone-based lifestyle weight loss program as completing 60% (6 from 10) of telephone health coaching calls. The primary outcomes for CACE analyses were pain intensity (0-10 Numerical Rating Scale) and disability (Roland Morris Disability Questionnaire for low back pain and Western Ontario and McMaster Universities Osteoarthritis Index for knee osteoarthritis). Secondary outcomes were weight, physical activity, and diet. We used an instrumental variable approach to estimate CACE in compliers. From the intervention groups of the trials, 29% of those with low back pain (n = 23/80) and 34% of those with knee osteoarthritis (n = 20/60) complied. Complier average causal effect estimates showed potentially clinically meaningful effects, but with low certainty because of wide confidence intervals, for pain intensity (-1.4; 95% confidence interval, -3.1, 0.4) and small but also uncertain effects for disability (-2.1; 95% confidence interval, -8.6, 4.5) among compliers in the low back pain trial intervention compared with control but not in the knee osteoarthritis trial. Our findings showed that compliers of a telephone-based weight loss intervention in the low back pain trial generally had improved outcomes; however, there were inconsistent effects in compliers from the knee osteoarthritis trial. Complier average causal effect estimates were larger than intention-to-treat results but must be considered with caution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.pain.0000000000002506DOI Listing
July 2022

The Virtues of Justice: Toward a Moral and Jurisprudential Psychology.

Int J Offender Ther Comp Criminol 2022 07 17;66(9):962-979. Epub 2021 Dec 17.

UNC Charlotte CLAS, NC, USA.

Within the theoretical literature on crime control and offender therapy, little has been written about the importance of virtue ethics in the experience of human justice and in the evolution of the common good. As a theory of being, the aretaic tradition extols eudemonic existence (i.e., excellence, flourishing) as a relational habit of developing character that is both practiced and embodied over time. What this implies is that virtue justice depends on a set of assumptions and predispositions-both moral and jurisprudential-whose meanings are essential to comprehending its psychological structure. This article sets out to explore several themes that our integral to our thesis on the virtues (i.e., the being) of justice. We reclaim justice's aretaic significance, critique the common conflation of justice and law, discuss how the dominant legalistic conception of justice is rooted in a particular view of human nature, suggest how justice might be more properly grounded in natural moral sensibilities, and provide a tentative explication of the psychological character of justice as a twofold moral disposition. Given this exploratory commentary, we conclude by reflecting on how individual well-being, system-wide progress, and transformative social change are both possible and practical, in the interest of promoting the virtues of justice within the practice of crime control and offender therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0306624X211066832DOI Listing
July 2022
-->