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Although there have been momentous and critical advancements in serious mental illness (SMI) psychology doctoral training models and competencies, there is still much systemic change needed to increase access to evidence-based SMI training for psychologists. In the last decade, there has been little to no growth or expansion of SMI training opportunities in clinical psychology doctoral programs in the United States, and psychologists are underrepresented in serving clients with SMI. As trainees and trainers committed to careers in SMI, the contributors aimed to identify barriers and facilitators throughout each stage of the SMI doctoral training pathway, including pregraduate school, graduate school, and internship to reflect critically on systemic issues that have impeded trainees from accessing the appropriate tools for SMI training. This conceptual article reviews the existing literature on barriers and facilitators to accessing SMI training. In centering trainee perspectives, the contributors also reflect on their own experiences through brief narratives illustrating the barriers and facilitators they have faced across training stages with existing empirical research. Recommendations made by the contributors include increasing access to financial support and mechanisms, diversifying departments and practicum sites to include SMI-focused training, and people in positions of power advocating for and centering trainee voices in departmental training decisions and development. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

The production of plutonium-238 through irradiation of neptunium-237 (237Np) target materials for the use in radioisotope thermoelectric generators is paramount for continued deep space exploration. This work employs scanning electron microscopy to analyze 237Np materials coupled with a well-developed image analysis framework (Morphological Analysis for Material Attribution, or MAMA) to determine the degree of micron-scale homogeneity in the materials. This work demonstrated how the quantification of particle characteristics can validate production materials and affirm the qualitative similarities observed in micrographs. The 237Np oxide particle analysis determined that the materials from five production runs were quantitatively homogenous (significant at α = 0.05) in particle area, circularity, equivalent circular diameter, and ellipse aspect ratio, with two of the sampling dates having statistically significant different means for one of the four characteristics. These metrics not only confirm general homogeneity of the material but also expand the application of MAMA workflows to 237Np materials, demonstrating the utility of MAMA analysis for a wider breadth of nuclear materials than previously reported. In the open literature, this study is the first time that these microanalytical techniques were applied to 237Np materials to this degree., Competing Interests: Conflict of Interest. The authors declare that they have no competing interest., (Published by Oxford University Press on behalf of the Microscopy Society of America 2024.)

Crystallization of alloys from a molten state is a fundamental process underpinning metallurgy. Here the direct imaging of an intermetallic precipitation reaction at equilibrium in a liquid-metal environment is demonstrated. It is shown that the outer layers of a solidified intermetallic are surprisingly unstable to the depths of several nanometers, fluctuating between a crystalline and a liquid state. This effect, referred to herein as crystal interface liquefaction, is observed at remarkably low temperatures and results in highly unstable crystal interfaces at temperatures exceeding 200 K below the bulk melting point of the solid. In general, any liquefaction process would occur at or close to the formal melting point of a solid, thus differentiating the observed liquefaction phenomenon from other processes such as surface pre-melting or conventional bulk melting. Crystal interface liquefaction is observed in a variety of binary alloy systems and as such, the findings may impact the understanding of crystallization and solidification processes in metallic systems and alloys more generally., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Low-melting liquid metals are emerging as a new group of highly functional solvents due to their capability to dissolve and alloy various metals in their elemental state to form solutions as well as colloidal systems. Furthermore, these liquid metals can facilitate and catalyze multiple unique chemical reactions. Despite the intriguing science behind liquid metals and alloys, very little is known about their fundamental structures in the nanometric regime. To bridge this gap, this work employs small angle neutron scattering and molecular dynamics simulations, revealing that the most commonly used liquid metal solvents, EGaIn and Galinstan, are surprisingly structured with the formation of clusters ranging from 157 to 15.7 Å. Conversely, noneutectic liquid metal alloys of GaSn or GaIn at low solute concentrations of 1, 2, and 5 wt%, as well as pure Ga, do not exhibit these structures. Importantly, the eutectic alloys retain their structure even at elevated temperatures of 60 and 90 °C, highlighting that they are not just simple homogeneous fluids consisting of individual atoms. Understanding the complex soft structure of liquid alloys will assist in comprehending complex phenomena occurring within these fluids and contribute to deriving reaction mechanisms in the realm of synthesis and liquid metal-based catalysis., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

The rise of antibiotic resistance in pathogenic bacteria requires new therapeutics to be developed. Several metallic nanoparticles such as those made from silver, copper, and zinc have shown significant antibacterial activity, in part due to metal ion leaching. Ga 3+ containing compounds have also been shown to have antibacterial properties. Accordingly, it is estimated that metallic Ga droplets may be antibacterial, and some studies to date have confirmed this. Here, multiple concentrations of Ga droplets were tested against the antibiotic resistant Gram-positive bacteria methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa) Despite a high concentration (2 mg/mL), Ga droplets had only modest antibacterial activity against both bacteria after 24 h of interaction. Finally, we demonstrated that Ga droplets were easily functionalized through a galvanic replacement reaction to develop antibacterial particles with copper and silver demonstrating a total detectable reduction of MRSA and >96% reduction of P. aeruginosa . Altogether, these results contradict previous literature and show that Ga droplets demonstrate no antibacterial activity at concentrations comparable to those of conventional antibiotics and well-established antibacterial nanomaterials and only modest antibacterial activity at very high concentrations. However, we demonstrate that their antibacterial activity can be easily enhanced by functionalization.

Introduction: South Asian refugees experience a high risk of obesity and diabetes yet are often underrepresented in studies on chronic diseases and their risk factors. The gut microbiota and gut permeability, as assessed through circulating lipopolysaccharide binding protein (LBP), may underlie the link between chronic inflammation and type 2 diabetes (T2D). The composition of the gut microbiota varies according to multiple factors including demographics, migration, and dietary patterns, particularly fiber intake. However, there is no evidence on the composition of the gut microbiota and its relationship with metabolic health in refugee populations, including those migrating to the United States from Bhutan. The objective of this study was to examine glycemic status in relation to LBP, systemic inflammation fiber intake, and gut microbiota composition in Bhutanese refugee adults residing in New Hampshire ( n = 50)., Methods: This cross-sectional study included a convenience sample of Bhutanese refugee adults ( N = 50) in NH. Established bioinformatics pipelines for metagenomic analysis were used to determine relative genus abundance, species richness, and alpha diversity measures from shallow shotgun sequences. The relationships between inflammatory markers, gut microbiota composition, dietary fiber, and glycemic status were analyzed., Results: We identified a substantial chronic disease burden in this study population, and observed a correlation between glycemic status, LBP, and inflammation, and a correlation between glycemic status and gut microbiome alpha diversity. Further, we identified a significant correlation between proinflammatory taxa and inflammatory cytokines. SCFA-producing taxa were found to be inversely correlated with age., Conclusion: To date, this is the most comprehensive examination of metabolic health and the gut microbiome in a Bhutanese refugee population in NH. The findings highlight areas for future investigations of inflammation and glycemic impairment, in addition to informing potential interventions targeting this vulnerable population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Moser, Moore, Khadka, Lyons, Foxall, Andam, Parker, Ochin, Garelnabi, Sevigny, Thomas, Bigornia and Dao.)

Background: Physical therapists use verbal cueing extensively during gait rehabilitation. Nevertheless, little is known about the ability of individuals post-stroke to make immediate changes to targeted spatiotemporal gait parameters from verbal commands. Additionally, adequate muscle strength may be necessary to promote positive alterations in gait., Objectives: To determine the influence of targeted verbal cues on spatiotemporal gait parameters for individuals with chronic stroke. Further, we assessed the potential of a relationship between cue-induced gait modifications and paretic lower limb strength., Methods: Using a within-subjects design, twenty-seven adults with chronic stroke walked over a pressure mat with verbal cues to walk at (1) comfortable and (2) fast speeds, with increased (3) arm swing, (4) foot height, (5) step length, (6) push off, and (7) cadence. We also assessed lower extremity strength using a hand-held dynamometer. We measured gait speed, step length, stance time, and cadence for comparisons between conditions and performed correlational analyses to assess the influence of strength on gait alterations., Results: Specific cues elicited increased walking speed, cadence, step lengths and paretic limb stance time. Only greater paretic hip and knee flexion strength was related to the ability to increase cadence when cued to do so (r > 0.41)., Conclusion: With targeted verbal cueing, clinicians can improve step length, gait speed, stance time and cadence for individuals with chronic stroke. Lower extremity strength does not appear to be related to the ability to alter gait with verbal cueing in individuals with chronic stroke.

The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Recent studies by others suggested that the genotype of the transporter protein ABCB6 contribute to the porphyria phenotype. Identifying the molecule(s) that are transported by ABCB6 has been problematic and has led to uncertainty with respect to how or if variants/mutants contribute to phenotypic heterogeneity. Knockout mouse models of Abcb6 have not provided a direction for investigation as homozygous knockout animals do not have a discrete phenotype. To address the proposed link between ABC6 genotype and porphyria phenotype, a large cohort of patients with acute hepatic porphyria and erythropoietic protoporphyria was analyzed. Our studies showed that ABCB6 genotype did not correlate with disease severity. Therefore, genotyping of ABCB6 in patients with acute hepatic porphyria and erythropoietic protoporphyria is not warranted., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

When more than one audible alarm is heard simultaneously, discrimination may be compromised. This experiment compares near-simultaneous clinical alarms in two styles, the first are the tonal 'melodies' from the 2012/2006 version of a global medical device safety standard (IEC 60601-1-8) and the second are the auditory-icon-style recommended in the 2020 version of the same standard. Sixty-six participants were required to identify the meaning and priority of four different clinical alarms for one of the two styles of alarm (between-subjects). Alarms sounded both singly and in pairs (within-subjects). Results showed that the auditory icon alarms outperformed the tonal alarms on all measures except one, both for overall accuracy (recognizing both priority and function) and for partial accuracy (recognizing priority or function but not both). The results add to the growing body of evidence supporting the use of auditory icon alarms in clinical environments., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The fashion industry cannot use 3 D Body Scanning to create custom garment patterns because its measurements fail to meet ISO 20685:2010's tolerances. To advance 3 D Body Scanning's precision, we present Gryphon: an algorithm that removes the two most extreme measurements from five body scans; removing potentially erroneous data. We assess Gryphon's precision against current industry practice, determine if consecutive and non-consecutive data capture influences precision, and determine 3 D Body Scanning's inherent imprecision inherent. We analyse 97 participants over 121 industry-standard measurements for consecutive and non-consecutive data-capture through MANOVA statistical analysis. Under current industry practice, only one measurement meets ISO 20685. However, under Gryphon and consecutive scanning, 97.5% of measurements meet ISO 20685. We also prove that the body's in-scan movement does not affect reliability. Ultimately, we offer the fashion industry, ergonomists, and practitioners an accessible method to increase 3 D Body Scanning's precision at a level unavailable under previous methods. Practitioner Summary: Ergonomists need precise data, yet we prove 0% of 3 D Body Scanning's measurements meet ISO 20685's tolerances. Our analysis of 97 participants scans, shows consecutive scanning is necessary to achieve data suitable for anthropometric applications. We develop the Gryphon process with consecutive scanning, making 97.3% of measurements meet ISO 20685. Abbreviations: ISO: International Organisation for Standards; Three Dimensional: 3D; MANOVA: Multivariate analysis of variance.

Portal hypertension (pHTN) complicates myeloproliferative neoplasms (MPNs), and usually occurs due to Budd-Chiari syndrome or splanchnic vein thrombosis. Current management modalities for MPN-associated pHTN include anticoagulation, transjugular intrahepatic portosystemic shunt (TIPS), and orthotopic liver transplant. Data on the thrombotic and bleeding outcomes of this practice is of poor quality, and whether direct oral anticoagulants (DOACs) are effective in this setting is unknown. We describe failure of DOACs to prevent post-TIPS complications in two case reports of patients with MPN-associated pHTN and review the associated literature. We conducted a comprehensive search in Embase (embase.com), Scopus (scopus.org), and PubMed for existing data on MPN-associated pHTN post-TIPS procedure. Four studies (n = 251) of patients with pHTN post-TIPS were eligible (MPN, n = 143). A review of the literature suggests that patients with MPN-associated pHTN may be at higher risk for post-TIPS complications including stent thrombosis and stenosis, compared with other causes of thrombotic pHTN. DOAC use has not been studied in this setting. While further studies to guide optimal management of MPN-associated pHTN post-TIPS are needed, available evidence suggests that life-long anticoagulation is warranted. DOACs should not be considered standard of care because of lack of evidence of efficacy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This paper demonstrates the effects of slight differences in measurement definitions on resultant body shape classification. Ergonomic researchers consider the Female Figure Identification Technique (FFIT) a 'gold standard' body shape classification system to describe variation in a population's 3 D profile. Nevertheless, researchers use FFIT without a scientific basis or considering their ergonomic suitability. This paper rigorously evaluates FFIT, focussing on ergonomics, garment construction, and scientific research applications. Through analysing 1,679 3 D Body Scans, we assess the level of agreement between the FFIT's body shape classification when measurements placed following FFIT's or SizeUK's guidance. We establish how different interpretations of FFIT's measurement placement cause the same body to be categorised into different shapes - in up to 40% of cases. FFIT omits shoulder measurements that have little relationship to body shape yet are vital in garment construction. Using FFIT with different datasets and definitions, therefore, leads to inconsistent conclusions about shape differences.

Clinical chaplains are exposed to varying degrees of suffering and are not exempt from suffering themselves. This study took a phenomenological approach to examining self-compassion among 11 clinical chaplains, all of which had suffered from personal and/or professional hardships while providing spiritual care to medical staff, patients, and families. The three elements of self-compassion are mindfulness, self-kindness, and common humanity. Results showed that clinical chaplains' understanding of the aspects of self-compassion are limited or non-existent. Participants in this study ardently shared their experiences as they related to self-care activities during times of personal hardship. However, the intentional implementation of self-compassion practice was not displayed in these narratives. The need for education in this area would prove to enhance self-awareness and overall self-care within the profession of clinical chaplaincy.

Background: Medical students must meet curricular expectations and pass national licensing examinations to become physicians. However, no previous studies explicitly modeled stages of medical students acquiring basic science knowledge. In this study, we employed an innovative statistical model to characterize students' growth using progress testing results over time and predict licensing examination performance., Methods: All students matriculated from 2016 to 2017 in our medical school with USMLE Step 1 test scores were included in this retrospective cohort study (N = 358). Markov chain method was employed to: 1) identify latent states of acquiring scientific knowledge based on progress tests and 2) estimate students' transition probabilities between states. The primary outcome of this study, United States Medical Licensing Examination (USMLE) Step 1 performance, were predicted based on students' estimated probabilities in each latent state identified by Markov chain model., Results: Four latent states were identified based on students' progress test results: Novice, Advanced Beginner I, Advanced Beginner II and Competent States. At the end of the first year, students predicted to remain in the Novice state had lower mean Step 1 scores compared to those in the Competent state (209, SD = 14.8 versus 255, SD = 10.8 respectively) and had more first attempt failures (11.5% versus 0%). On regression analysis, it is found that at the end of the first year, if there was 10% higher chance staying in Novice State, Step 1 scores will be predicted 2.0 points lower (95% CI: 0.85-2.81 with P < .01); while 10% higher chance in Competent State, Step 1scores will be predicted 4.3 points higher (95% CI: 2.92-5.19 with P < .01). Similar findings were also found at the end of second year medical school., Conclusions: Using the Markov chain model to analyze longitudinal progress test performance offers a flexible and effective estimation method to identify students' transitions across latent stages for acquiring scientific knowledge. The results can help identify students who are at-risk for licensing examination failure and may benefit from targeted academic support.

Normal human red blood cells have an average life span of about 120 days in the circulation after which they are engulfed by macrophages. This is an extremely efficient process as macrophages phagocytose about 5 million erythrocytes every second without any significant release of hemoglobin in the circulation. Despite large number of investigations, the precise molecular mechanism by which macrophages recognize senescent red blood cells for clearance remains elusive. Red cells undergo several physicochemical changes as they age in the circulation. Several of these changes have been proposed as a recognition tag for macrophages. Most prevalent hypotheses for red cell clearance mechanism(s) are expression of neoantigens on red cell surface, exposure phosphatidylserine and decreased deformability. While there is some correlation between these changes with aging their causal role for red cell clearance has not been established. Despite plethora of investigations, we still have incomplete understanding of the molecular details of red cell clearance. In this review, we have reviewed the recent data on clearance of senescent red cells. We anticipate recent progresses in in vivo red cell labeling and the explosion of modern proteomic techniques will, in near future, facilitate our understanding of red cell senescence and their destruction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Thiagarajan, Parker and Prchal.)

Erythropoietic protoporphyria (EPP), the most common porphyria of childhood and the third most common porphyria of adulthood, is characterized clinically by painful, non-blistering cutaneous photosensitivity. Two distinct inheritance patterns involving mutations affecting genes that encode enzymes of the heme biosynthetic pathway underlie the clinical phenotype. Aminolevulinic acid synthase 2 (ALAS2), the rate limiting enzyme of the heme pathway in the erythron, is a therapeutic target in EPP because inhibiting enzyme function would reduce downstream production of protoporphyrin IX (PPIX), preventing accumulation of the toxic molecule and thereby ameliorating symptoms. Isoniazid (INH) is widely used for treatment of latent and active M. tuberculosis (TB). Sideroblastic anemia is observed in some patients taking INH, and studies have shown that this process is a consequence of inhibition of ALAS2 by INH. Based on these observations, we postulated that INH might have therapeutic activity in patients with EPP. We challenged this hypothesis in a murine model of EPP and showed that, after 4 weeks of treatment with INH, both plasma PPIX and hepatic PPIX were significantly reduced. Next, we tested the effect of INH on patients with EPP. After eight weeks, no significant difference in plasma or red cell PPIX was observed among the 15 patients enrolled in the study. These results demonstrate that while INH can lower PPIX in an animal model of EPP, the standard dose used to treat TB is insufficient to affect levels in humans., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Mucosotropic human papillomaviruses (HPVs) cause prevalent anogenital infections, some of which can progress to cancers. It is imperative to identify efficacious drug candidates, as there are few therapeutic options. We have recapitulated a robust productive program of HPV-18 in organotypic raft cultures of primary human keratinocytes. The HPV E7 protein induces S phase reentry, along with DNA damage response (DDR) in differentiated cells to support viral DNA amplification. A number of small molecule inhibitors of DDR regulators are in clinical use or clinical trials to treat cancers. Here, we used our raft culture system to examine effects of inhibitors of ATR/Chk1 and ATM/Chk2 on HPV infection. The inhibitors impaired S-phase reentry and progression as well as HPV DNA amplification. The Chk1 inhibitor MK-8776 was most effective, reducing viral DNA amplification by 90-99% and caused DNA damage and apoptosis, preferentially in HPV infected cells. We found that this sensitivity was imparted by the E7 protein and report that MK-8776 also caused extensive cell death of cervical cancer cell lines. Furthermore, it sensitized the cells to cisplatin, commonly used to treat advanced cervical cancer. Based on these observations, the Chk1 inhibitors could be potential effective agents to be re-purposed to treat the spectrum of HPV infections in single or combination therapy.

Romiplostim is a thrombopoietin receptor agonist approved for the treatment of immune thrombocytopenia purpura. When following FDA-approved romiplostim prescribing recommendations to withhold treatment for platelet counts above 400k/µL, some patients exhibit a precipitous decline in their platelet count potentially causing patient harm. We present two cases where stable platelet counts were achieved only through persistent weekly dosing of romiplostim despite platelet counts above 400k/µL on the day of administration. Therefore, continuous weekly dosing of romiplostim despite platelet count being above 400k/µL combined with twice weekly vigilant monitoring is an alternative method of romiplostim dosing that mitigates severe fluctuations in platelets. We also discuss important details, postulated mechanisms, and evidence-based mitigation strategies.

Introduction: Communities That Care, refined and tested for more than 25years, offers a step-by-step coalition-based approach to promote well-being and prevent risk behaviors among youth. Communities That Care guides coalitions to identify and prioritize underlying risk and protective factors; set specific, measurable community goals; adopt tested, effective prevention programs to target selected factors; and implement chosen programs with fidelity. Communities That Care has been implemented in a variety of communities, but has only recently begun to be systematically evaluated in diverse, urban communities., Methods: This paper presents a process evaluation of Communities That Care implementation within a Midwestern ethnically diverse, urban community. In-depth surveys of 25 black male youth aged 8-14years and their caregivers were conducted to determine the degree to which coalition-selected priorities aligned with the experience of black families. Implementation and survey data were collected in 2014-2017 and analyzed in 2017-2018., Results: Roughly 30% of youth reported ever being bullied or bullying someone else on school property; this aligned with the coalition's decision to focus on positive social skills and bullying prevention. Additional data aligned with the coalition's intent to expand its community action plan to encompass other priorities, including family transitions and mobility. For example, roughly one third of caregivers went on welfare and one third of families moved to a new home or apartment in the past year., Conclusions: In communities whose residents have experienced historical and current inequities, an effective community prevention plan may need to address structural as well as social determinants of well-being among youth and their families., Supplement Information: This article is part of a supplement entitled African American Men's Health: Research, Practice, and Policy Implications, which is sponsored by the National Institutes of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: This manuscript highlights initial activities from a 5-year project to build a community coalition focused on the promotion of family, school, and community connectedness; academic investment; and social and emotional well-being among black male youth and their families, as well as the prevention and reduction of risk behaviors. Project activities were planned according to the step-by-step coalition-based prevention system, Communities That Care., Methods: During Year 1 (2013/2014), semi-structured interviews were conducted with 14 community members (parents, school administrators and teachers, and community leaders and volunteers) to evaluate readiness to adopt Communities That Care. Participants were asked to (1) define community; (2) identify community strengths; (3) recommend methods to strengthen community relationships; (4) envision ideal coalition functions; (5) identify current community resources; (6) recommend prevention targets and methods; (7) identify potential barriers to coalition participation; and (8) assess overall community readiness to adopt Communities That Care. Analyses were conducted in Year 3 (2015/2016)., Results: Participants expressed eagerness and readiness to adopt Communities That Care. They identified community strengths and local resources that could contribute to coalition success, as well as potential barriers to participation and group cohesion that if left unaddressed could diminish coalition impact. Participants believed that links between multiple environments (home, school, community) should be strengthened in order to promote the well-being of youth. They envisioned the Communities That Care coalition as a task force of community members with varying talents invested in youth across their entire life course., Conclusions: Community members' insights may be used to guide implementation of Communities That Care by this coalition and others., Supplement Information: This article is part of a supplement entitled African American Men's Health: Research, Practice, and Policy Implications, which is sponsored by the National Institutes of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction and Aim: We sought to identify independent risk factors for cirrhosis in HFE p.C282Y homozygotes in a cross-sectional study., Material and Methods: We evaluated 368 p.C282Y homozygotes who underwent liver biopsy and compared characteristics of those with and without cirrhosis. We performed multivariable logistic regression on cirrhosis with: age; sex; race/ethnicity; diabetes; blood pints/units donated voluntarily; erythrocyte pints/units received; iron supplement use; alcohol intake, g/d; body mass index, kg/m2; swollen/tender 2nd/3rd metacarpophalangeal joints; elevated alanine aminotransferase; elevated aspartate aminotransferase; steatosis/fatty liver; iron removed by phlebotomy, g; and GNPAT p.D519G positivity., Results: Mean age of 368 participants (73.6% men) was 47 ± 13 (standard deviation) y. Cirrhosis was diagnosed in 86 participants (23.4%). Participants with cirrhosis had significantly greater mean age, proportion of men, diabetes prevalence, mean daily alcohol intake, prevalence of swollen/ tender 2nd/3rd metacarpophalangeal joints, mean serum ferritin, elevated alanine aminotransferase, elevated aspartate aminotransferase, and mean iron removed; and significantly fewer mean blood pints/units donated. GNPAT p.D519G positivity was detected in 82 of 188 participants (43.6%). In a multivariable model for cirrhosis, there were four significant positive associations: age (10-y intervals) (odds ratio 2.2 [95% confidence interval 1.5, 3.3]); diabetes (3.3; [1.1, 9.7]); alcohol intake (14 g alcohol drinks/d) (1.5 [1.2, 1.8]); and iron removed, g (1.3 [1.2, 1.4]). There was no statistical evidence of two-way interactions between these variables., Conclusion: In conclusion, cirrhosis in HFE p.C282Y homozygotes is significantly associated with age, diabetes, daily alcohol intake, and iron removed by phlebotomy, taking into account the effect of other variables.

Introduction: Medical students often do not value attending in-person large group sessions. It is also not clear from prior research whether attendance at large group sessions impact on performance in medical school. The goal of this study was to assess the relationship between voluntary attendance in large group sessions organized as a "flipped classroom" in a new innovative curriculum and students' mastery of clinical applications of basic science knowledge., Methodology: Our students' ability to apply basic science knowledge to clinical problems is assessed via progress testing using three methodologies: a locally developed multiple-choice examination, written examination developed through the National Board of Medical Examiners (NBME) Customized Assessment Services Program and post encounter questions included in a clinical skills examination. We analyzed the relationship between voluntary attendance at weekly large group "flipped classroom" sessions and the students' performance on examinations given at four intervals over the initial 24-week module of the medical school curriculum., Results: Complete data were available for 167 students. A total of 82 students (49.1%) attended all large group sessions, 65 students (38.9%) missed one or two sessions and 20 students (12.0%) missed three or more sessions. There were no difference between the students in the groups on their medical admission (MCAT) examination scores. The growth in performance from each time point until the next was statistically significant. There was no statistically significant difference in growth between the students who had no absences and those who had one or two absences. Students who missed three or more sessions performed significantly lower than their peers over the 24 week module and were more likely to score one or more standard deviations below the class mean on the assessments., Conclusions: We found no relationship between attendance and MCAT scores suggesting the differences in performance on the progress tests was not due to initial differences in knowledge or reasoning skills. While the study was not experimental, it suggests large group sessions using a "flipped classroom" approach to provide reinforcement, feedback and practice may be effective for increasing learning and retention in the application of basic science knowledge among first year medical students., Competing Interests: The authors declare there are no competing interests.

Previous work suggested that hemoglobin (Hb) tetramer formation slows autoxidation and hemin loss and that the naturally occurring mutant, Hb Providence (HbProv; βK82D), is much more resistant to degradation by H 2 O 2 We have examined systematically the effects of genetic cross-linking of Hb tetramers with and without the HbProv mutation on autoxidation, hemin loss, and reactions with H 2 O 2 , using native HbA and various wild-type recombinant Hbs as controls. Genetically cross-linked Hb Presbyterian (βN108K) was also examined as an example of a low oxygen affinity tetramer. Our conclusions are: (a) at low concentrations, all the cross-linked tetramers show smaller rates of autoxidation and hemin loss than HbA, which can dissociate into much less stable dimers and (b) the HbProv βK82D mutation confers more resistance to degradation by H 2 O 2 , by markedly inhibiting oxidation of the β93 cysteine side chain, particularly in cross-linked tetramers and even in the presence of the destabilizing Hb Presbyterian mutation. These results show that cross-linking and the βK82D mutation do enhance the resistance of Hb to oxidative degradation, a critical element in the design of a safe and effective oxygen therapeutic., (© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Ergonomic measurement is central to product design and development; especially for body worn products and clothing. However, there is a large variation in measurement definitions, complicated by new body scanning technology that captures measurements in a posture different to traditional manual methods. Investigations of hip measurement definitions in current clothing measurement practices supports analysis of the effect of scan posture and hip measurement definition on the circumferences of the hip. Here, the hip girth is a key clothing measurement that is not defined in current body scanning measurement standards. Sixty-four participants were scanned in the standard scan posture of a [TC] 2 body scanner, and also in a natural posture similar to that of traditional manual measurement collection. Results indicate that scan posture affects hip girth circumferences, and that some current clothing measurement practices may not define the largest lower body circumference. Recommendations are made concerning how the hip is defined in measurement practice and within body scanning for clothing product development. Practitioner Summary: The hip girth is an important measurement in garment design, yet its measurement protocol is not currently defined. We demonstrate that body posture during body scanning affects hip circumferences, and that current clothing measurement practices may not define the largest lower body circumference. This paper also provides future measurement practice recommendations.

Background: GNPAT p.D519G positivity is significantly increased in HFE p.C282Y homozygotes with markedly increased iron stores. We sought to determine associations of p.D519G and iron-related variables with iron stores in p.C282Y homozygotes., Methods: We defined markedly increased iron stores as serum ferritin >2247pmol/L (>1000μg/L) and either hepatic iron >236μmol/g dry weight or iron >10g by induction phlebotomy (men and women). We defined normal or mildly elevated iron stores as serum ferritin <674.1pmol/L (<300μg/L) or either age≥40y with iron ≤2.5g iron by induction phlebotomy or age≥50y with ≤3.0g iron by induction phlebotomy (men only). We compared participant subgroups using univariate methods. Using multivariable logistic regression, we evaluated associations of markedly increased iron stores with these variables: age; iron supplement use (dichotomous); whole blood units donated; erythrocyte units received as transfusion; daily alcohol consumption, g; and p.D519G positivity (heterozygosity or homozygosity)., Results: The mean age of 56 participants (94.6% men) was 55±10 (SD) y; 41 had markedly increased iron stores. Prevalences of swollen/tender 2nd/3rd metacarpophalangeal joints and elevated aspartate or alanine aminotransferase were significantly greater in participants with markedly increased iron stores. Only participants with markedly increased iron stores had cirrhosis. In multivariable analyses, p.D519G positivity was the only exposure variable significantly associated with markedly increased iron stores (odds ratio 9.9, 95% CI [1.6, 60.3], p=0.0126)., Conclusions: GNPAT p.D519G is strongly associated with markedly increased iron stores in p.C282Y homozygotes after correction for age, iron-related variables, and alcohol consumption., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Once suspected, the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) is straightforward when flow cytometric analysis of the peripheral blood reveals a population of glycosyl phosphatidylinositol anchor protein-deficient cells. But PNH is clinically heterogeneous, with some patients having a disease process characterized by florid intravascular, complement-mediated hemolysis, whereas in others, bone marrow failure dominates the clinical picture with modest or even no evidence of hemolysis observed. The clinical heterogeneity is due to the close, though incompletely understood, relationship between PNH and immune-mediated bone marrow failure, and that PNH is an acquired, nonmalignant clonal disease of the hematopoietic stem cells. Bone marrow failure complicates management of PNH because compromised erythropoiesis contributes, to a greater or lesser degree, to the anemia; in addition, the extent to which the mutant stem cell clone expands in an individual patient determines the magnitude of the hemolytic component of the disease. An understanding of the unique pathobiology of PNH in relationship both to complement physiology and immune-mediated bone marrow failure provides the basis for a systematic approach to management., (© 2016 by The American Society of Hematology. All rights reserved.)

Both familial and sporadic porphyria cutanea tarda (PCT) are iron dependent diseases. Symptoms of PCT resolve when iron stores are depleted by phlebotomy, and a sequence variant of HFE (C282Y, c.843G>A, rs1800562) that enhances iron aborption by reducing hepcidin expression is a risk factor for PCT. Recently, a polymorphic variant (D519G, c.1556A>G, rs11558492) of glyceronephosphate O-acyltransferase (GNPAT) was shown to be enriched in male patients with type I hereditary hemochromatosis (HFE C282Y homozygotes) who presented with a high iron phenotype, suggesting that GNPAT D519G, like HFE C282Y, is a modifier of iron homeostasis that favors iron absorption. To challenge this hypothesis, we investigated the frequency of GNPAT D519G in patients with both familial and sporadic PCT. Patients were screened for GNPAT D519G and allelic variants of HFE (both C282Y and H63D). Nucleotide sequencing of uroporphyrinogen decarboxylase (URO-D) identified mutant alleles. Patients with low erythrocyte URO-D activity or a damaging URO-D variant were classified as familial PCT (fPCT) and those with wild-type URO-D were classified as sporadic PCT (sPCT). GNPAT D519G was significantly enriched in the fPCT patient population (p = 0.0014) but not in the sPCT population (p = 0.4477). Both HFE C282Y and H63D (c.187C>G, rs1799945) were enriched in both PCT patient populations (p<0.0001) but showed no greater association with fPCT than with sPCT., Conclusion: GNPAT D519G is a risk factor for fPCT, but not for sPCT., Competing Interests: The authors have declared that no competing interests exist.

Diagnostic genetic testing for hereditary hemochromatosis is readily available for clinically relevant HFE variants (i.e., those that generate the C282Y, H63D and S65C HFE polymorphisms); however, genetic testing for other known causes of iron overload, including mutations affecting genes encoding hemojuvelin, transferrin receptor 2, HAMP, and ferroportin is not. As an alternative to conventional genetic testing we propose diagnostic use of whole exome sequencing for characterization of non-HFE hemochromatosis. To illustrate the effectiveness of whole exome sequencing as a diagnostic tool, we present the case of an 18-year-old female with a probable case of juvenile hemochromatosis, who was referred for specialty care after testing negative for commonly occurring HFE variants. Whole exome sequencing offered complete coverage of target genes and is a fast, cost effective diagnostic tool for characterization of non-HFE hemochromatosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by increased complement-mediated lysis of erythrocytes (RBCs) because of low/absent glycophosphatidylinositol (GPI) anchors of numerous cell surface proteins., Methods: Rare event analysis was applied to 120 million RBCs (12 normal individuals) and 102 million RBCs (102 normal individuals) to establish a reference range and verify a methodology for rare event analysis. Patient PNH testing (n = 10,984) was performed over 47 months using the 2010 consensus guidelines with CD59-PE and glycophorin A-FITC for RBCs and FLAER-Alexa 488, CD33-PerCP-Cy5.5, CD15-APC, CD14-APC-Cy7, and CD24-PE for WBCs., Results: The distribution of CD59- RBCs in the normal population was asymmetric with a mean of 5.9, median between 3 and 4, and mode of 2 per million RBCs. The normal range of CD59- RBCs was 0-17/million RBCs. A natural cutoff of 2.5% of the peak expression of CD59 delineates CD59+ from CD59- populations. The incidence of GPI- samples received by the laboratory was 6-7% without correlation to age (P = 0.35) or sex (P = 0.45). The percentage of GPI- neutrophils and monocytes were strongly correlated (R(2) = 0.96) and usually greater than the percentage of GPI- RBCs., Conclusion: PNH RBC testing is a good example of rare event analysis applied to clinical cytometry—only 2.5 min are required to collect 1 million RBCs. With an established normal range of CD59- RBCs, the correlation between total cell count and sensitivity for detecting an abnormal population can be calculated using Poisson statistics., (© 2015 International Clinical Cytometry Society.)

Bordetella pertussis is the causative agent of whooping cough. This pathogenic bacterium can obtain the essential nutrient iron using its native alcaligin siderophore and by utilizing xeno-siderophores such as desferrioxamine B, ferrichrome, and enterobactin. Previous genome-wide expression profiling identified an iron repressible B. pertussis gene encoding a periplasmic protein (FbpABp). A previously reported crystal structure shows significant similarity between FbpABp and previously characterized bacterial iron binding proteins, and established its iron-binding ability. Bordetella growth studies determined that FbpABp was required for utilization of not only unchelated iron, but also utilization of iron bound to both native and xeno-siderophores. In this in vitro solution study, we quantified the binding of unchelated ferric iron to FbpABp in the presence of various anions and importantly, we demonstrated that FbpABp binds all the ferric siderophores tested (native and xeno) with μM affinity. In silico modeling augmented solution data. FbpABp was incapable of iron removal from ferric xeno-siderophores in vitro. However, when FbpABp was reacted with native ferric-alcaligin, it elicited a pronounced change in the iron coordination environment, which may signify an early step in FbpABp-mediated iron removal from the native siderophore. To our knowledge, this is the first time the periplasmic component of an iron uptake system has been shown to bind iron directly as Fe(3+) and indirectly as a ferric siderophore complex.

Objective: The contribution of sexual transmission to genital Candida infection remains unclear. This study sought to investigate whether sexual behaviours were associated with the presence of genital Candida species among a cohort of women who have sex with women (WSW) in addition to determining the genetic concordance of genital Candida spp. among WSW in sexual partnerships., Methods: WSW ≥18 years of age presenting to the Mississippi State Department of Health STD Clinic during 2009-2010 completed a sexual behaviour survey. Culture of vaginal fluid was performed for Candida spp. identification; associations with participant characteristics were determined using logistic regression analysis. Random amplified polymorphic DNA (RAPD) PCR was performed on DNA extracted from yeast cultures of WSW in sexual partnerships in which both partners had isolates of Candida spp. identified and among a set of age/sexual behaviour matched controls. RAPD genetic fingerprints were evaluated by hierarchical cluster analysis for concordance., Results: Genital Candida spp. were isolated in 105/196 (53.6%) of women: 13/105 (12.4%) had symptomatic vulvovaginal candidiasis while 92/105 (87.6%) had asymptomatic vaginal colonisation. Bisexual identity, sex with women and men during the past 12 months and numbers of male sexual partners during the past 12 months were the only significant predictors of genital Candida spp. in bivariate analysis. 13 pairs of WSW in sexual partnerships in which both partners had genital Candida spp. and 11 WSW with genital Candida spp. not in sexual partnerships were identified. Candida spp. RAPD banding patterns were discordant for all isolates among WSW within partnerships and in controls., Conclusions: This study found no evidence supporting sexual transmission of genital Candida spp. between women.

This paper investigates the influence of presenting volunteered and professionally created geographic information to 101 wheelchair users through an interactive website that included information collected by wheelchair-using volunteers. The aim of this experiment was to understand the influence that (1) knowing a map-based website contains volunteered information and (2) actually including volunteered information within an online interactive map (a mashup) have on the perceived trust of the user, described in terms of quality and authority. Analysis using Kruskal-Wallis showed that judgements of currency were influenced by including geo-information from untrained volunteers (volunteered geographic information) within the mashup, but not influenced by the participant being told that the online map contained volunteered information. The participants appeared to make judgements based on what information they saw, rather than what they were told about the source of the information., Practitioner Summary: Since 2004, information services have combined crowdsourced (volunteered) alongside professional information within online interactive maps. An online experiment presented both of these information types to wheelchair users within a travel context. Including volunteered information was shown to increase the perceptions of how up-to-date the maps were.

This paper explored the question of how volunteered and professional geographic information (VGI and PGI) can be used together in an outdoor recreation context. In particular, consideration is given to what makes each information source valuable to the user, and how this can be used to help developers of GIS provide more useful, usable and satisfying products. The assumption that VGI is inferior to PGI is shown to be unfounded; rather each has its own strengths in describing particular aspects of the user information landscape. Considering the opportunities to influence user activities, both VGI and PGI have a greater ability to influence the user in the planning phase than actually during the activity. The importance of the author of the information (volunteer or professional) is shown to be of less importance to the end-user than the characteristics which describe the information in terms of communication, frequency of updates and accessibility., (Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

Boron in the ocean is generally considered a nonbiological element due to its relatively high concentration (0.4 mM) and depth independent concentration profile. Here we report an unexpected role for boron in the iron transport system of the marine bacterium Marinobacter algicola. Proteome analysis under varying boron concentrations revealed that the periplasmic ferric binding protein (Mb-FbpA) was among the proteins whose expression was most affected, strongly implicating the involvement of boron in iron utilization. Here we show that boron facilitates Fe(3+) sequestration by Mb-FbpA at pH 8 (oceanic pH) by acting as a synergistic anion (B(OH)4(1-)). Fe(3+) sequestration does not occur at pH 6.5 where boric acid (B(OH)3; pK(a) = 8.55) is the predominant species. Borate anion is also shown to bind to apo-Mb-FbpA with mM affinity at pH 8, consistent with the biological relevance implied from boron's oceanic concentration (0.4 mM). Borate is among those synergistic anions tested which support the strongest Fe(3+) binding to Mb-FbpA, where the range of anion dependent affinity constants is log K'(eff) = 21-22. Since the pKa of boric acid (8.55) lies near the pH of ocean water, changes in oceanic pH, as a consequence of fluctuations in atmospheric CO2, may perturb iron uptake in many marine heterotrophic bacteria due to a decrease in oceanic borate anion concentration.