CT esophagogram in the emergency setting: typical findings and suggested workflow.

PURPOSE: Esophageal perforation (EP) can be a diagnostic challenge. Computed tomography (CT) and CT esophagography (CTE) are often used to rule out EP in the emergency setting with promising diagnostic performance, but the standard of care remains fluoroscopic esophagography (FE). We assess the diagnostic performance of CT and CTE when interpreted by expert and generalist radiologists and created an imaging workflow guide. METHODS: Retrospective study of patients presenting with suspected EP. Two expert radiologists independently reviewed blinded CT/CTE studies, recorded CT findings, and assigned an esophageal injury grade. We also collected initial (general radiologist) CT findings and interpretation and FE diagnoses. We assessed inter-reader reliability and diagnostic performance. RESULTS: EP was diagnosed in 46/139 (33%) encounters. The most common CT/CTE findings in EP were esophageal wall thickening (46/46, 100%), pneumomediastinum (42/46, 91%), and mediastinal stranding (39/46, 85%). CT and CTE sensitivity for detecting EP was 89% and 89% for expert radiologists, respectively, and 79% and 82% for general radiologists, compared with 46% for FE. Inter-reader agreement for detecting EP by CT and CTE was kappa 0.35 and 0.42 (both p < .001) between expert and generalist radiologists. We present radiographic images for key CT/CTE findings and a suggested workflow for the evaluation of possible EP. CONCLUSION: CT and CTE are more sensitive than FE for EP in the emergency setting. Due to the rarity of EP and current wide variability in imaging interpretation, an imaging workflow and injury grading system based on esophageal and mediastinal CT findings are offered to help guide management.

Probabilistic reaction norm reveals family-related variation in the association between size, condition, and sexual maturation onset in Atlantic salmon (Salmo salar).

This study investigated the relationship between the size, condition, year class, family, and sexual maturity of Atlantic salmon (Salmo salar) using data collected in an aquaculture selective breeding programme. Males that were sexually mature at 2 years of age (maiden spawn) have, on average, greater fork length and condition factor (K) at 1 year of age than their immature counterparts. For every 10-mm increase in fork length or 0.1 increase in K at 1 year of age, the odds of sexual maturity at 2 years of age increased by 1.48 or 1.22 times, respectively. Females that were sexually mature at 3 years of age (maiden spawn) have, on average, greater fork length and K at 2 years of age than their immature counterparts. For every 10-mm increase in fork length or 0.1 increase in K at 2 years of age, the odds of sexual maturity at 3 years of age increased by 1.06 or 1.44 times, respectively. The family explained 34.93% of the variation in sexual maturity among 2-year-old males that was not attributable to the average effects of fork length and K at 1 year of age and year class. The proportion of variation in sexual maturity among 3-year-old females explained by the family could not be investigated. These findings suggest that the onset of sexual maturation in Atlantic salmon is conditional on performance (with respect to energy availability) surpassing a threshold, the magnitude of which can vary between families and is determined by a genetic component. This could support the application of genetic selection to promote or inhibit the onset of sexual maturation in farmed stocks.

Automated Bioanalytical Workflow for Ligand Binding-Based Pharmacokinetic Assay Development.

The growth of therapeutic monoclonal antibodies (mAbs) continues to accelerate due to their success as treatments for many diseases. As new therapeutics are developed, it is increasingly important to have robust bioanalytical methods to measure the pharmacokinetics (PK) of circulating therapeutic mAbs in serum. Ligand-binding assays such as enzyme-linked immunosorbent assays (ELISAs) with anti-idiotypic antibodies (anti-IDs) targeting the variable regions of the therapeutic antibody are sensitive and specific bioanalytical methods to measure levels of therapeutic antibodies in a biological matrix. However, soluble circulating drug mAb targets can interfere with the anti-IDs binding to the therapeutic mAb, thereby resulting in an underestimation of total drug concentration. Therefore, in addition to a high binding affinity for the mAb, the selection of anti-IDs and the assay format that are not impacted by soluble antigens and have low matrix interference is essential for developing a robust PK assay. Standardized automated approaches to screen and select optimal reagents and assay formats are critical to increase efficiency, quality, and PK assay robustness. However, there does not exist an integrated screening and analysis platform to develop robust PK assays across multiple formats. We have developed an automated workflow and scoring platform with multiple bioanalytical assay parameters that allow for ranking of candidate anti-IDs. A primary automated indirect electrochemiluminescence (ECL) was utilized to shortlist the anti-IDs that were selected for labeling and screening in pairs. A secondary screen using an ECL sandwich assay with labeled-anti-ID pairings was used to test multiple PK assay formats to identify the best anti-ID pairing/PK assay format. We developed an automated assay using fixed plate maps combined with a human-guided graphical user interface-based scoring system and compared it to a data-dependent scoring system using Gaussian mixture models for automated scoring and selection. Our approach allowed for screening of anti-IDs and identification of the most robust PK assay format with significantly reduced time and resources compared with traditional approaches. We believe that such standardized, automated, and integrated platforms that accelerate the development of PK assays will become increasingly important for supporting future human clinical trials.

Participant experiences using novel home-based blood collection device for viral load testing in HIV cure trials with analytical treatment interruptions

Background: HIV cure-directed clinical trials using analytical treatment interruptions (ATIs) require participants to adhere to frequent monitoring visits for viral load tests. Novel viral load monitoring strategies are needed to decrease participant burden during ATIs.Objective: To examine acceptability of a novel home-based blood collection device for viral load testing in the context of two ongoing ATI trials in Philadelphia, PA, United States.Methods: From January 2021 to February 2022, participants completed three in-depth interviews via teleconference during their participation in an ATI: (1) within two weeks of enrollment in the device study, (2) approximately four weeks after beginning to use the device, and (3) within two weeks of the end of the ATI when ART was re-initiated. We used conventional content analysis to analyze the data.Results: We recruited 17 participants: 15 were cisgender males, 1 cisgender female, and 1 transgender woman. We observed an overall 87% success rate in drawing blood with the device from home collection and found overall high acceptance of the device. A mean of 91.5 devices per participant were used for home-based blood collection. Most PWH viewed the device as relatively convenient, painless, easy to use, and a simple solution to frequent blood draws. The main challenge encountered was the inability to completely fill up devices with blood in some cases. Most participants reported positive experiences with mailing blood samples and could see themselves using the device on a regular basis outside of ATIs.Conclusions: Our study showed participant valued the novel home-based peripheral blood collection for viral load testing in the context of ATI trials. More research will be necessary to optimize implementation of the device and to assess whether blood collected can reliably measure viral loads in the context of ATI trials.

Developmental changes in gene expression and gonad morphology during sex differentiation in Atlantic salmon (Salmo salar).

The Atlantic salmon (Salmo salar) is a globally important species for its value in fisheries and aquaculture, and as a research model. In order to characterise aspects of sex differentiation at the morphological and mRNA level in this species, the present study examined developmental changes in gonad morphology and gene expression in males and females between 0 and 79 days post hatch (dph). Morphological differentiation of the ovary (indicated by the formation of germ cell cysts) became apparent from 52 dph. By 79 dph, ovarian phenotype was evident in 100% of genotypic females. Testes remained in an undifferentiated-like state throughout the experiment, containing germ cells dispersed singularly within the gonadal region distal to the mesentery. There were no significant sex-related differences in gonad cross-section size, germ cell number or germ cell diameter during the experiment. The expression of genes involved in teleost sex differentiation (anti-müllerian hormone (amh), cytochrome P450, family 19, subfamily A, polypeptide 1a (cyp19a1a), forkhead box L2a (foxl2a), gonadal soma-derived factor (gsdf), r-spondin 1 (rspo1), sexually dimorphic on the Y chromosome (sdY)), retinoic acid-signalling (aldehyde dehydrogenase 1a2 (aldh1a2), cytochrome P450 family 26 a1 (cyp26a1), cytochrome P450 family 26 b1 (cyp26b1), t-box transcription factor 1 (tbx1a)) and neuroestrogen production (cytochrome P450, family 19, subfamily A, polypeptide 1b (cyp19a1b)) was investigated. Significant sex-related differences were observed only for the expression of amh, cyp19a1a, gsdf and sdY. In males, amh, gsdf and sdY were upregulated from 34, 59 and 44 dph respectively. In females, cyp19a1a was upregulated from 66 dph. Independent of sex, foxl2a expression was highest at 0 dph and had reduced âˆ¼ 47-fold by the time of morphological sex differentiation at 52 dph. This study provides new insights into the timing and sequence of some physiological changes associated with sex differentiation in Atlantic salmon. These findings also reveal that some aspects of the mRNA sex differentiation pathways in Atlantic salmon are unique compared to other teleost fishes, including other salmonids.

"We are looking at the future right now": community acceptability of a home-based viral load test device in the context of HIV cure-related research with analytical treatment interruptions in the United States.

BACKGROUND: People with HIV (PWH) and community members have advocated for the development of a home-based viral load test device that could make analytical treatment interruptions (ATIs) less burdensome. OBJECTIVE: We assessed community acceptability of a novel home-based viral load test device. METHODS: In 2021, we conducted 15 interviews and 3 virtual focus groups with PWH involved in HIV cure research. We used conventional thematic analysis to analyze the data. RESULTS: PWH viewed the home-based viral load test device as a critical adjunct in ongoing HIV cure trials with ATIs. The ability to test for viral load at home on demand would alleviate anxiety around being off ART. Participants drew parallels with glucometers used for diabetes. A preference was expressed for the home-based test to clearly indicate whether one was detectable or undetectable for HIV to mitigate risk of HIV transmission to partners. Perceived advantages of the device included convenience, sense of control, and no puncturing of veins. Perceived concerns were possible physical marks, user errors and navigating the logistics of mailing samples to a laboratory and receiving test results. Participants expressed mixed effects on stigma, such as helping normalize HIV, but increased potential for inadvertent disclosure of HIV status or ATI participation. Increasing pluri-potency of the device beyond viral load testing (e.g., CD4+ count test) would increase its utility. Participants suggested pairing the device with telemedicine and mobile health technologies. CONCLUSIONS: If proven effective, the home-based viral load test device will become a critical adjunct in HIV cure research and HIV care.

Preliminary Acceptability of a Home-Based Peripheral Blood Collection Device for Viral Load Testing in the Context of Analytical Treatment Interruptions in HIV Cure Trials: Results from a Nationwide Survey in the United States.

Frequent viral load testing is necessary during analytical treatment interruptions (ATIs) in HIV cure-directed clinical trials, though such may be burdensome and inconvenient to trial participants. We implemented a national, cross-sectional survey in the United States to examine the acceptability of a novel home-based peripheral blood collection device for HIV viral load testing. Between June and August 2021, we distributed an online survey to people with HIV (PWH) and community members, biomedical HIV cure researchers and HIV care providers. We performed descriptive analyses to summarize the results. We received 73 survey responses, with 51 from community members, 12 from biomedical HIV cure researchers and 10 from HIV care providers. Of those, 51 (70%) were cisgender men and 50 (68%) reported living with HIV. Most (>80% overall) indicated that the device would be helpful during ATI trials and they would feel comfortable using it themselves or recommending it to their patients/participants. Of the 50 PWH, 42 (84%) indicated they would use the device if they were participating in an ATI trial and 27 (54%) also expressed a willingness to use the device outside of HIV cure studies. Increasing sensitivity of viral load tests and pluri-potency of the device (CD4 count, chemistries) would augment acceptability. Survey findings provide evidence that viral load home testing would be an important adjunct to ongoing HIV cure-directed trials involving ATIs. Survey findings may help inform successful implementation and uptake of the device in the context of personalized HIV care.

Publisher Correction: Discordance for genotypic sex in phenotypic female Atlantic salmon (Salmo salar) is related to a reduced sdY copy number.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Discordance for genotypic sex in phenotypic female Atlantic salmon (Salmo salar) is related to a reduced sdY copy number.

The master sex determinant in rainbow trout (Oncorhynchus mykiss), sexually dimorphic on the Y chromosome (sdY), is strongly but not perfectly associated with male phenotype in several other species from the family Salmonidae. Currently, the cause and implications of discordance for sdY-predicted genotypic sex and phenotypic sex in these species is unclear. Using an established multiplex PCR test for exons 2 and 3 of sdY, we demonstrated that sdY-predicted genotypic sex was discordant with histologically evidenced phenotypic sex in 4% of 176 Tasmanian Atlantic salmon. All discordant individuals were phenotypic females presenting a male genotype. Using real-time qPCR assays that we developed and validated for exons 2, 3 and 4 of sdY, all genotype-phenotype discordant females were confirmed to possess sdY, albeit at a reduced number of copies when compared to phenotypic males. The real-time qPCR assays also demonstrated reduced levels of sdY in 30% of phenotypic females that the established multiplex PCR-based test indicated to be devoid of sdY. These findings suggest sdY may be reduced in copy number or mosaicked in the genomic DNA of sdY-positive phenotypic female Atlantic salmon and highlight the importance of understanding the effects of reduced sdY copies on the development of phenotypic sex.

Bivalent rLP2086 (Trumenba®): Development of a well-characterized vaccine through commercialization.

The phrase "Process is the Product" is often applied to biologics, including multicomponent vaccines composed of complex components that evade complete characterization. Vaccine production processes must be defined and locked early in the development cycle to ensure consistent quality of the vaccine throughout scale-up, clinical studies, and commercialization. This approach of front-loading the development work helped facilitate the accelerated approval of the Biologic License Application for the well-characterized vaccine bivalent rLP2086 (Trumenba®, Pfizer Inc) in 2014 under Breakthrough Therapy Designation. Bivalent rLP2086 contains two rLP2086 antigens and is licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B in individuals 10-25years of age in the United States. This paper discusses the development of the manufacturing process of the two antigens for the purpose of making it amenable to any manufacturing facility. For the journey to commercialization, the operating model used to manage this highly accelerated program led to a framework that ensured "right the first time" execution, robust process characterization, and proactive process monitoring. This framework enabled quick problem identification and proactive resolutions, resulting in a robust control strategy for the commercial process.

Process development of a FGF21 protein-antibody conjugate.

A scalable, viable process was developed for the Fibroblast Growth Factor 21 (FGF21) protein-antibody conjugate, CVX-343, an extended half-life therapeutic for the treatment of metabolic disease. CVX-343 utilizes the CovX antibody scaffold technology platform that was specifically developed for peptide and protein half-life extension. CVX-343 is representative of a growing number of complex novel peptide- and protein-based bioconjugate molecules currently being explored as therapeutic candidates. The complexity of these bioconjugates, assembled using well-established chemistries, can lead to very difficult production schemes requiring multiple starting materials and a combination of diverse technologies. Key improvements had to be made to the original CVX-343 Phase 1 manufacturing process in preparation for Phase 3 and commercial manufacturing. A strategy of minimizing FGF21A129C dimerization and stabilizing the FGF21A129C Drug Substance Intermediate (DSI), linker, and activated FGF21 intermediate was pursued. The use of tris(2-carboxyethyl)phosphine (TCEP) to prevent FGF21A129C dimerization through disulfide formation was eliminated. FGF21A129C dimerization and linker hydrolysis were minimized by formulating and activating FGF21A129C at acidic instead of neutral pH. An activation use test was utilized to guide FGF21A129C pooling in order to minimize misfolds, dimers, and misfolded dimers in the FGF21A129C DSI. After final optimization of reaction conditions, a process was established that reduced the consumption of FGF21A129C by 36% (from 4.7 to 3.0 equivalents) and the consumption of linker by 55% (from 1.4 to 0.95 equivalents for a smaller required amount of FGF21A129C ). The overall process time was reduced from ∼5 to ∼3 days. The product distribution improved from containing ∼60% to ∼75% desired bifunctionalized (+2 FGF21) FGF21-antibody conjugate in the crude conjugation mixture and from ∼80% to ∼85% in the final CVX-343 Drug Substance (DS), while maintaining the same overall process yield based on antibody scaffold input.

Comparison of intramedullary nail, plate, and external fixation in the treatment of distal tibia nonunions.

PURPOSE: The purpose of this study was to examine time to union of extra-articular distal tibia nonunions based on fracture type and fixation methods: intramedullary nail (IMN), plate osteosynthesis (PO), and external fixation (EF). METHODS: This retrospective chart review included all patients who presented at a Level I trauma center with AO/OTA 43A & distal third 42A-C fracture nonunions between 2008 and 2014. Fixation methods were recorded and patient course was followed until nonunion had healed clinically. RESULTS: Thirty-three distal tibia nonunions were included, and 29 reached eventual union (88%). Five AO/OTA fracture types were present. Mean times to union from nonunion diagnosis between original fracture types were compared (p = 0.203). Comminuted fracture types had longer times to union from nonunion diagnosis compared to simple fracture types (78 vs. 46 weeks, p = 0.051) and more revision fixations (1.5 vs. 0.5, p = 0.037). Mean time to union from nonunion diagnosis was shorter when no revision fixation was done compared to revisions (15 vs. 42 weeks, p = 0.102). Times to union from nonunion diagnosis without revision fixation were: IMN (12 weeks), PO (27 weeks), and EF (13 weeks) (p = 0.202). Times to union from definitive revision fixation were: IMN (17 weeks), PO (21 weeks), and EF (66 weeks) (p = 0.009), with EF taking significantly longer than both other methods. 21 patients (64%) underwent revision fixation. Revision fail rates were: IMN (0/6, 0%), PO (2/8, 25%), and EF (15/21, 71%). Time to union was longer in revisions that changed fixation method compared to revisions that used the same method (51 vs. 18 weeks, p = 0.030). Deep infections were also associated with longer union times (81 vs. 47 weeks, p = 0.040). CONCLUSIONS: In this nonunion population, comminuted fracture types needed more time and revisions to reach union. Time to union was only clinically shorter when revision fixation was not performed, but IMN and PO were both successful fixation options with significantly shorter times to union than EF. Mean time to union increased even more when revision of fixation method was performed vs. exchange revision, as did nonunions with deep infections.

Diabetes and bone health: latest evidence and clinical implications.

As the prevalence of diabetes is increasing worldwide, research on some of the lesser-known effects, including impaired bone health, are gaining a lot of attention. The two most common forms of diabetes are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). These two differ in their physiology, with T1DM stemming from an inability to produce insulin, and T2DM involving an insufficient response to the insulin that is produced. This review aims to highlight the most current information regarding diabetes as it relates to bone health. It looks at biochemical changes that characterize diabetic bone; notably increased adiposity, altered bone metabolism, and variations in bone mineral density (BMD). Then several hypotheses are analyzed, concerning how these changes may be detrimental to the highly orchestrated processes that are involved in bone formation and turnover, and ultimately result in the distinguishing features of diabetic bone. The review proceeds by explaining the effects of antidiabetes medications on bone health, then highlighting several ways that diabetes can play a part in other clinical treatment outcomes. With diabetes negatively affecting bone health and creating other clinical problems, and its treatment options potentiating these effects, physicians should consider the use of anti-osteoporotic drugs to supplement standard anti-diabetes medications in patients suffering with diabetic bone loss.

Inhibition of the Nuclear Export Receptor XPO1 as a Therapeutic Target for Platinum-Resistant Ovarian Cancer.

Purpose: The high fatality-to-case ratio of ovarian cancer is directly related to platinum resistance. Exportin-1 (XPO1) is a nuclear exporter that mediates nuclear export of multiple tumor suppressors. We investigated possible clinicopathologic correlations of XPO1 expression levels and evaluated the efficacy of XPO1 inhibition as a therapeutic strategy in platinum-sensitive and -resistant ovarian cancer.Experimental Design: XPO1 expression levels were analyzed to define clinicopathologic correlates using both TCGA/GEO datasets and tissue microarrays (TMA). The effect of XPO1 inhibition, using the small-molecule inhibitors KPT-185 and KPT-330 (selinexor) alone or in combination with a platinum agent on cell viability, apoptosis, and the transcriptome was tested in immortalized and patient-derived ovarian cancer cell lines (PDCL) and platinum-resistant mice (PDX). Seven patients with late-stage, recurrent, and heavily pretreated ovarian cancer were treated with an oral XPO1 inhibitor.Results: XPO1 RNA overexpression and protein nuclear localization were correlated with decreased survival and platinum resistance in ovarian cancer. Targeted XPO1 inhibition decreased cell viability and synergistically restored platinum sensitivity in both immortalized ovarian cancer cells and PDCL. The XPO1 inhibitor-mediated apoptosis occurred through both p53-dependent and p53-independent signaling pathways. Selinexor treatment, alone and in combination with platinum, markedly decreased tumor growth and prolonged survival in platinum-resistant PDX and mice. In selinexor-treated patients, tumor growth was halted in 3 of 5 patients, including one with a partial response, and was safely tolerated by all.Conclusions: Taken together, these results provide evidence that XPO1 inhibition represents a new therapeutic strategy for overcoming platinum resistance in women with ovarian cancer. Clin Cancer Res; 23(6); 1552-63. ©2016 AACR.

Annual colonoscopy volume and maintenance of competency for surgeons.

INTRODUCTION: To determine whether the annual case volume of general surgeons (greater or less than 200 colonoscopies) is associated with quality outcomes. METHODS: This retrospective cohort study involved all adults who underwent colonoscopy by a surgeon in the city of St. John's, NL, during the first 6 months of 2012. Subjects were identified through records from the health authority, and data were recorded on a standardized data sheet. Univariate analysis followed by stepwise multivariable logistic regression was performed to determine whether there was an association between quality outcomes (colonoscopy completion rate, adenoma detection rate) and predictors of these outcomes including annual colonoscopy volume, patient age, gender, indication for colonoscopy, and ASA score. A Chi-squared test was used to determine whether other outcomes were associated with annual colonoscopy volume. RESULTS: Data were collected on 1060 patients. Mean age was 59.5 (sd 12.2) years with 550 females. A total of 13 surgeons were studied, of which 7 performed less than 200 annual colonoscopies over the previous 2 years (low-volume group) and 6 performed more than 200 annual colonoscopies over the previous 2 years (high-volume group). While there was a significant difference in the colonoscopy completion rate favoring the high-volume group (82.2 vs. 91.1 %, p < 0.001), no difference was noted in the adenoma detection rate between groups (16.7 vs. 17.7 %, p = 0.762). The regression model revealed that colonoscopy completion was also associated with an indication of screening or surveillance and an ASA score of 1 or 2. The adenoma detection rate was associated with older age and male gender. There was no statistically significant association between annual colonoscopy volume and other safety outcome measures. CONCLUSION: Performing over 200 colonoscopies annually is associated with higher colonoscopy completion rates, but does not appear to be associated with other quality measures.

Effect of Colonoscopy Volume on Quality Indicators.

Background. The purpose of this study is to determine if colonoscopy quality is associated with the annual case volume of endoscopists. Methods. A retrospective cohort study was performed on 3235 patients who underwent colonoscopy in the city of St. John's, NL, between January and June 2012. Data collected included completion of colonoscopy (CCR) and adenoma detection rates (ADR). Endoscopists were divided into quintiles based on annual case volume. To account for potential confounding variables, univariate analyses followed by multivariable logistic regression were used to identify variables independently associated with CCR and ADR. Results. A total of 13 surgeons and 8 gastroenterologists were studied. There was a significant difference in CCR (p < 0.001) and ADR (p < 0.001) based on annual volume. Following multivariable regression, predictors of successful colonoscopy completion included annual colonoscopy volume, lower age, male sex, an indication of screening or surveillance, and a low ASA score. Predictors of adenoma detection included older age, male sex, an indication of screening or surveillance, and gastroenterology specialty. Conclusion. Higher annual case volume is associated with better quality of colonoscopy in terms of completion. However, gastroenterology specialty appears to be a better predictor of ADR than annual case volume.

Development of a Nutrition Screening Tool for an Outpatient Wound Center.

OBJECTIVE: To construct a quickly and easily administered nutrition screening tool using variables believed to be predictive of malnutrition risk in the wound patient population. DESIGN: A prospective pilot study assessed patients on a list of suspected variables, as well as the Scored Patient-Generated Subjective Global Assessment (PG-SGA), chosen as the criterion standard. Variables were analyzed to select the most appropriate items for inclusion on a new nutrition screening tool using preliminary bivariate correlations and χ tests of association. Items significantly associated with malnutrition were dichotomized, and binary logistic regression analyses were performed to arrive at a final model. A sum score was computed, and receiver operating characteristic analysis was used to determine designation of risk. SETTING: An outpatient wound center in Northeast Ohio. PARTICIPANTS: The pilot study included a convenience sample of 105 outpatients with at least 1 active wound. MAIN OUTCOME MEASURES: Malnutrition as assessed by the Scored PG-SGA. MAIN RESULTS: The final nutrition screening tool, the MEAL Scale, is composed of 4 dichotomous elements: multiple wounds (number of wounds), eats less than 3 meals per day, appetite decrease (eats less than usual), and level of activity. These variables predicted 83.7% of the malnutrition cases assessed by the Scored PG-SGA. The receiver operating characteristic analysis showed an acceptable area under the curve (0.8581), and a cutoff score of 2 or greater was selected to indicate risk (median sensitivity = 91.4%, median specificity = 60.9%). CONCLUSIONS: Although further studies of validity and reliability are necessary to establish the tool before widespread use, the MEAL Scale is a needed step toward nutrition screening in a wound patient population.

Does the hands-on, technical training of residents in colonoscopy affect quality outcomes?

INTRODUCTION: The training of residents in colonoscopy has become an important topic as more attention is being paid to quality outcomes. PURPOSE: To determine whether colonoscopy quality outcomes are adversely affected by allowing residents to perform colonoscopies under supervision. METHODS: This retrospective cohort study was performed on all adults who underwent colonoscopy in the city of St. John's, NL, from January to June 2012 by an endoscopist who trains residents. Subjects were identified through records from the health authority. Data were extracted from the electronic medical record, including the endoscopy procedure report, the nursing record of the endoscopy, and the pathology report. Data were recorded on a standardized data sheet and entered into SPSS version 19.0 for analysis. A Chi-squared test was used for categorical data and a t test was used for continuous data. RESULTS: A total of 867 cases involving seven endoscopists and three trainees were studied. The colonoscopy was performed by an endoscopist in 673 cases and performed by a trainee in 194 cases. Mean age [59.3 (SD 12.44) years] and gender (51.7% female) were similar between groups. There was no difference in cecal intubation rate (90.6 vs. 89.2%, p = 0.544) between endoscopists and trainees. There was a difference in polyp detection (23.3 vs. 33.5%, p = 0.004) and adenoma detection (12.8 vs. 22.7%, p = 0.034) favoring the trainees. There was no difference in the average dose of Fentanyl given (98.4 vs. 94.9 mg, p = 0.066), but there was less use of Versed favoring the trainee group (3.59 vs. 3.31 mg, p = 0.002). There was no difference in the endoscopy nurses' perception of patient discomfort between groups (28.7 vs. 26.7%, p = 0.632). CONCLUSION: The presence of a trainee does not appear to adversely affect quality outcomes in colonoscopy. When the polyp and adenoma detection rates of endoscopists are low, the addition of a trainee may improve these detection rates.

Expression analysis of sex-determining pathway genes during development in male and female Atlantic salmon (Salmo salar).

We studied the expression of 28 genes that are involved in vertebrate sex-determination or sex-differentiation pathways, in male and female Atlantic salmon (Salmo salar) in 11 stages of development from fertilization to after first feeding. Gene expression was measured in half-sibs that shared the same dam. The sire of family 1 was a sex-reversed female (i.e., genetically female but phenotypically male), and so the progeny of this family are all female. The sire of family 2 was a true male, and so the offspring were 50% male and 50% female. Gene expression levels were compared among three groups: 20 female offspring of the cross between a regular female and the sex-reversed female (family 1, first group), ∼ 10 females from the cross between a regular female and a regular male (family 2, second group) and ∼ 10 males from this same family (family 2, third group). Statistically significant differences in expression levels between males and the two groups of females were observed for two genes, gsdf and amh/mis, in the last four developmental stages examined. SdY, the sex-determining gene in rainbow trout, appeared to be expressed in males from 58 days postfertilization (dpf). Starting at 83 dpf, ovarian aromatase, cyp19a, expression appeared to be greater in both groups of females compared with males, but this difference was not statistically significant. The time course of expression suggests that sdY may be involved in the upregulation of gsdf and amh/mis and the subsequent repression of cyp19a in males via the effect of amh/mis.

Registered report: Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases.

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered report describes the proposed replication plan of key experiments from 'Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases' by Xu and colleagues, published in Cancer Cell in 2011 (Xu et al., 2011). The key experiments being replicated include Supplemental Figure 3I, which demonstrates that transfection with mutant forms of IDH1 increases levels of 2-hydroxyglutarate (2-HG), Figures 3A and 8A, which demonstrate changes in histone methylation after treatment with 2-HG, and Figures 3D and 7B, which show that mutant IDH1 can effect the same changes as treatment with excess 2-HG. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife.