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This review analyzes the experiences of patients and clinicians with regards to international cross-border reproductive care (CBRC) for the purpose of conception.Electronic databases PubMed, Embase, Web of Science, and Scopus were searched using 'medical tourism' AND 'assisted reproductive technology' from 1978 to 2020.Predominant patient motivators for CBRC were cost and legality of assisted reproduction technology (ART) in one's home country, followed by cultural factors like shared language, religion, and cultural familiarity. Clinicians suggested global laws for CBRC would reduce the potential for exploitation of vulnerable populations but believed the enactment of international regulations unlikely and, even if enacted, difficult to enforce.While patient and clinician experiences with CBRC varied, patients frequently cited financial and legal reasons for pursuing CBRC, while many providers had concern for the patient's safety.This review recommends clinicians involved in family planning counsel patients seeking treatment abroad by: (i) informing patients of the risks and benefits of treatment abroad, (ii) establishing guidelines and standards for clinicians on resuming patient care post-CBRC, and (iii) creating a directory of reputable CBRC clinicians and experts.

Patients with primary sclerosing cholangitis (PSC) commonly undergo ileal pouch-anal anastomosis (IPAA) for medically-refractory ulcerative colitis (UC) or colorectal dysplasia. Pouchitis develops more frequently in patients with PSC, potentially leading to increased morbidity. We aimed to assess clinical characteristics and treatment outcomes for pouchitis in patients with PSC compared to a matched, non-PSC cohort.All patients with PSC who underwent IPAA and were diagnosed with pouchitis (PSC-pouchitis) were identified. A matched cohort composed of non-PSC patients who underwent IPAA for UC and subsequently developed pouchitis (UC-pouchitis) was developed. Relevant demographic, clinical, endoscopic, histologic, and treatment data were collected and compared between groups.Of those with PSC-pouchitis (n=182), 53.9% and 46.1% underwent IPAA for medically-refractory disease and dysplasia, respectively, compared to 88.7% and 11.3% in the UC-pouchitis group (P.001). Patients with PSC-pouchitis were more likely to develop chronic pouchitis (68.1% vs 34.1%; P.001), have moderate-to-severe pouch inflammation (54.9% vs 32.4%; P.001), and prepouch ileitis (34.1% vs 11.5%; P.001) compared to UC-pouchitis. Of those with PSC-pouchitis, 50.6% and 17.6% developed chronic antibiotic-dependent or antibiotic-refractory pouchitis, respectively, compared to 25.8% and 7.7% with UC-pouchitis. There was no difference in treatment response between the two groups with use of thiopurines, anti-tumor necrosis factor agents, and newer biologics.PSC-associated pouchitis presents with a unique clinical phenotype, characterized by increased risk of chronic pouchitis, moderate-to-severe pouch inflammation, prepouch ileitis, and less response to conventional antimicrobial therapy.

Purpose To investigate patient-level factors associated with first-line glaucoma therapy with laser trabeculoplasty (LT) versus topical medication. Design Population-based study. Participants All patients 66 years of age and older in Ontario, Canada, receiving first-ever therapy for glaucoma with either LT or topical medication between April 1, 2007, and March 31, 2019. Methods Linked health care databases were used to identify patients receiving first-line glaucoma therapy and to ascertain patient-level factors potentially associated with receipt of LT versus medication. Multivariate logistic regression analyses were undertaken. Main Outcome Measures Factors associated with receiving LT versus medications were evaluated using adjusted odds ratios (ORs) for age, gender, previous cataract surgery, previous corneal transplantation, previous retina surgery, level of systemic comorbidity, socioeconomic status (SES), and rural versus urban residence. Results In total, 194 759 patients were included. Older patients were less likely to be treated with LT versus medication (≥81 years of age vs. 66–70 years of age: OR, 0.49; 95% confidence interval [CI], 0.48–0.50), whereas women were more likely than men to receive LT (OR, 1.42; 95% CI, 1.39–1.45). Previous ocular surgeries were associated with decreased probability of treatment with LT, including cataract surgery (OR, 0.31; 95% CI, 0.30–0.32), corneal transplantation (OR, 0.39; 95% CI, 0.31–0.49), and retina surgery (OR, 0.46; 95% CI, 0.41–0.51). Patients with high comorbidity were less likely to receive LT (highest vs. lowest level of comorbidity: OR, 0.94; 95% CI, 0.91–0.97). Laser trabeculoplasty use was less likely among patients at higher levels of SES (highest vs. lowest level: OR, 0.86; 95% CI, 0.84–0.89) and from a rural residence (versus urban: OR, 0.92; 95% CI, 0.90–0.95). Increasing utilization of LT over time was noted (for each additional calendar year: OR, 1.05 per year; 95% CI, 1.05–1.05 per year). Conclusions Our results identified patient characteristics associated with use of LT as primary therapy for glaucoma, including factors related to patient demographics, ocular history, and comorbidity. Many of these associations are unexpected based on efficacy data or evidence-based guidelines. These results are topical considering growing evidence supporting use of first-line LT.

Purpose To quantify healing rates and patient-reported outcome scores following repair of radial meniscus tears. Methods PubMed, Scopus, and Embase databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria included: human subjects with meniscal tears, full-text English language, average follow-up of at 1 year, and publication after the 2000. Exclusion criteria included technical, biomechanical, and cadaveric studies. Study quality was assessed using Coleman Methodology Scores and Methodological Index for Non-Randomized Studies (MINORS) criteria. Results Twelve studies reported on the repair of 243 radial tears in 241 patients. The mean Modified Coleman Methodology Score was 46.8, range 26-60, with a mean level of evidence of 3.5. Arthroscopic techniques were used in all studies, with 1 study using an arthroscopic-assisted 2-tunnel trans-tibial pullout technique. The mean patient age was 32 years (11-71). The mean follow-up was 35 months (12 to 75.6). The average time to surgery was 10.9 months (0.5-22.4). Eight of the 12 studies reported concomitant anterior cruciate ligament (ACL) reconstruction, with 64% having concomitant ACL injury. The most common outcome measure was the Lysholm score, which improved from 47-68.9 preoperatively to 86.4-95.6 postoperatively. Tegner Activity Scale improved from 2.5-3.1 preoperatively to 4.7-6.7 postoperatively. Healing rates were reported via magnetic resonance imaging and second-look arthroscopy. Second-look arthroscopy was performed for a variety of indications, including removal of screw, washers or plates, dissatisfaction with original procedure, partial healing found on magnetic resonance imaging, or desire of the patient to know the true healing status before return to sport. Of those assessed, 62.0% had complete healing, 30.0% partial healing, and 8.0% failure to heal. Conclusions Patient-reported outcomes of radial meniscus repair with and without ACL reconstruction are encouraging, with high patient-reported outcomes reported at final follow-up when compared with preoperative scores. Among all meniscus repairs assessed for healing, the majority demonstrated at least some healing with an overall low rate of failure. Level of Evidence IV; systematic review of level III-IV studies.

Objectives Sexual and gender minority (SGM) individuals experience cancer-related health disparities and reduced quality of cancer care compared to the general population in part due to a lack of knowledgeable providers. This study explored oncologists’ experiences and perspectives in providing patient-centered care for SGM individuals with cancer. Methods We conducted a qualitative analysis of oncologists’ responses to four open-ended items on a national survey eliciting their experiences, reservations, and suggestions in treating SGM patients. Results Over 50 % of the 149 respondents of the national survey responded to at least one open-ended item. Many oncologists reported positive experiences reflecting personal growth and affirmative care practices, such as open, non-judgmental communication, compassion, competence, and supporting patients’ identity. There was a notable lack of experience with transgender patients in particular. Lack of knowledge, interpersonal communication concerns (e.g., fear of offending patients), and microaggressions (“don’t ask, don’t tell”) were identified as barriers to providing affirming care. Conclusions Oncologists recognize their knowledge deficits and need strategies to overcome communication barriers and microaggressions among the cancer care team to provide SGM-affirming care. Practice implications Curricula are needed to train oncologists in SGM healthcare needs and affirming communication skills to facilitate patient-centered care for SGM individuals with cancer.

Graphical abstract, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections remain unmanageable in some parts of the world. As with other RNA viruses, mutations in the SARS-CoV-2 gene have been continuously evolving. Recently, four variants have been identified, B.1.1.7, B.1.351, P.1 and CAL.20C. These variants appear to be more infectious and transmissible than the original Wuhan-Hu-1 virus. Using a combination of bioinformatics and structural analyses, we show that the new SARS-CoV-2 variants emerged in the background of an already known Spike protein mutation D614G together with another mutation P323L in the RNA polymerase of SARS-CoV-2. The phylogenetic analysis showed that the CAL.20C and B.1.351 shared one common ancestor, whereas the B.1.1.7 and P.1 shared a different ancestor. Structural comparisons did not show any significant difference between the wild-type and mutant ACE2/Spike complexes. Structural analysis indicated that the N501Y mutation may increase hydrophobic interactions at the ACE2/Spike interface. However, reported greater binding affinity of N501Y Spike with ACE2 does not seem to be entirely due to increased hydrophobic interactions, given that Spike mutation R417T in P.1 or K417N in B.1.351 results in the loss of a salt-bridge interaction between ACE2 and S-RBD. The calculated change in free energy did not provide a clear trend of S protein stability of mutations in the variants. As expected, we show that the CAL.20C generally migrated from the west coast to the east coast of the USA. Taken together, the analyses suggest that the evolution of variants and their infectivity is complex and may depend upon many factors.

INTRODUCTION: Transgender and gender diverse people often face discrimination and may experience disproportionate emotional distress, leading to suicide attempts. It is, therefore, essential to estimate the frequency and potential determinants of suicide attempts among transgender and gender diverse individuals. METHODS: Longitudinal data on 6,327 transgender and gender diverse individuals enrolled in three integrated healthcare systems were analyzed to assess suicide attempt rates. Incidence was compared in transmasculine and transfeminine people, by age and race/ethnicity and according to mental health status at baseline. Cox proportional hazards models examined rates and predictors of suicide attempts during follow-up. Data were collected in 2016 and analyses were conducted in 2019. RESULTS: During follow-up, 4.8% of transmasculine and 3.0% of transfeminine patients had at least one suicide attempt. Suicide attempt rates were more than seven times higher among patients aged 45 years, more than three times higher among those with previous history of suicide ideation or suicide attempts compared with patients with no such history, and two to five times higher among those with one to two mental health diagnoses and more than two mental health diagnoses at baseline versus those with none. CONCLUSIONS: Among transgender and gender diverse inviduals, younger people, those with prior suicidal ideation or attempts, and those with multiple mental health diagnoses are at higher risk for suicide attempts. Future research should examine the impact of gender-affirming healthcare use on risk of suicide attempts and identify targets for suicide prevention interventions among transgender and gender diverse people in clinical settings.

The process of gender affirmation may have an impact on fertility. Counseling on the impact of affirmation and opportunities for fertility, future family building, and reproductive health is an important first step in the affirmation process. This article discusses the options for fertility preservation for transmen. The barriers and outcomes in this unique population are also considered. In addition, insights are provided on the future of fertility preservation and suggestions are made for how to build a comprehensive team for male transgender patients.

Introduction The purpose of this study was to test the hypothesis that patients with Medicaid insurance or Medicaid-like coverage would have longer times to follow-up and be less likely to complete colonoscopy compared with patients with commercial insurance within the same healthcare systems. Methods A total of 35,009 patients aged 50–64years with a positive fecal immunochemical test were evaluated in Northern and Southern California Kaiser Permanente systems and in a North Texas safety-net system between 2011 and 2012. Kaplan–Meier estimation was used between 2016 and 2017 to calculate the probability of having follow-up colonoscopy by coverage type. Among Kaiser Permanente patients, Cox regression was used to estimate hazard ratios and 95% CIs for the association between coverage type and receipt of follow-up, adjusting for sociodemographics and health status. Results Even within the same integrated system with organized follow-up, patients with Medicaid were 24% less likely to complete follow-up as those with commercial insurance. Percentage receiving colonoscopy within 3 months after a positive fecal immunochemical test was 74.6% for commercial insurance, 63.10% for Medicaid only, and 37.5% for patients served by the integrated safety-net system. Conclusions This study found that patients with Medicaid were less likely than those with commercial insurance to complete follow-up colonoscopy after a positive fecal immunochemical test and had longer average times to follow-up. With the future of coverage mechanisms uncertain, it is important and timely to assess influences of health insurance coverage on likelihood of follow-up colonoscopy and identify potential disparities in screening completion.

© 2018 Elsevier B.V. Phosphorus is an essential part of the world food web and a non-substitutable nutrient in all biological systems. Losses of phosphorus occur along the food-supply chain and cause environmental degradation and eutrophication. A key global challenge is to meet rising worldwide food demand while protecting water and environmental quality, and seeking to manage uncertainty around potential future phosphorus price or supply shocks. This paper presents a stakeholder-generated conceptual model of potential transformative change for implementing phosphorus sustainability on the island of Ireland via an ‘All-Island Phosphorus Sustainability’ workshop. Key transition pathways identified by stakeholders included: incentivising phosphorus recovery, developing collaborative networks to facilitate change, developing markets and value chains for recovered products; implementing data-informed practices on-farm to prevent losses and increase efficiencies, and harmonisation of technologies with end-user needs. A comparable model was previously produced for the North American region. We describe consensus and differences around key priorities between the two regions’ conceptual models, and assess how the model produced for the island of Ireland can effect system-wide change and policy moving forward. Many of the transitional pathways and future aspirations presented in both models resonate globally and are highly pertinent to other jurisdictions.

Transgender individuals may experience impaired fertility due to gender-affirming hormonal interventions (e.g., pubertal suppression treatment and/or exogenous hormones). Clinical practice guidelines recommend providers discuss fertility implications and options for fertility preservation. The goal of this study was to examine fertility knowledge, practice behaviors, and perceived barriers to fertility care among multidisciplinary providers who care for transgender pediatric and/or adult patients.A 46-item survey was distributed to relevant listservs and at conferences with a focus on transgender health.Two hundred two providers completed the survey: (1) physicians (n = 87), (2) psychologists (n = 51), (3) Master (MA)-level mental health providers (n = 39), and (4) nonphysician healthcare providers, comprising advanced practice nurses, registered nurses, and physician assistants (n = 25). Overall knowledge was high (M = 3.64, SD = 1.61). Significant differences were identified in knowledge by provider type (p.001) but not patient age group (p = .693). Physicians had significantly greater knowledge than MA-level mental health providers (p = .005). Variables associated with fertility discussion included provider-related barriers [b = -.42, p.001], and perceived patient-related barriers, including perceptions that patients are unwilling to delay treatment [b = .12, p = .011] or are unable to afford fertility preservation (FP) [b = .12, p = .029].While overall fertility-related knowledge was high, there was variability in domains of knowledge, as well as provider practice behaviors related to fertility counseling and referral for FP. Findings related to perceived barriers to fertility counseling and fertility preservation warrant further investigation; qualitative studies may be particularly helpful in understanding how specific provider- and patient-related barriers impact counseling and referral for fertility-related care.

Background Physicians are encouraged through formalized systems to discuss their own errors with peers for the purposes of quality improvement. However, no clear professional norms exist regarding peer review when physicians discover errors that occurred at other institutions before referral. Our objective was to determine specialist physicians’ attitudes and practices regarding providing feedback to referring physicians when prereferral errors are discovered. Methods We conducted semistructured interviews of specialists from two National Cancer Institute–designated Cancer Centers. Thematic analysis of transcripts was performed to determine physicians' attitudes toward the delivery of negative feedback regarding prereferral errors, whether and how they communicate these errors to referring physicians, and perceived barriers to doing so. Results We purposively sampled specialists by discipline, gender, and experience level, who described greater than 50% reliance on external referrals (n = 30). Specialists believed regular, explicit feedback was ideal, but the majority of participants reported practices that did not meet this standard. While there were some structural barriers to providing feedback (lack of time or contact information), the majority of barriers were internal psychological concerns (general discomfort with providing negative feedback, fear of conflict, or defensive reactions) or fears about implications for future referrals or medicolegal risk. Conclusions Policies and interventions that structure the approach to this sometimes difficult, yet critically important, opportunity for reducing medical errors warrant investigation as potential mechanisms by which to improve consistency and quality of care while maintaining positive professional relationships.

Genomic wide association studies identified the CACNA1C locus as genetically associated with both schizophrenia and bipolar affective disorder. CACNA1C encodes Cav1.2, one of four subunits of L-type voltage gated calcium channels. Variation resides in non-coding regions of CACNA1C which interact with the promoter and are validated expression quantitative trait loci. Using reporter gene constructs we demonstrate the CACNA1C promoter is a major mediator of inducible regulation of CACNA1C activity in the SH-SY5Y neuroblastoma cell line. Exposure of SH-SY5Y cells to lithium and cocaine modulated both the endogenous CACNA1C gene and the promoter in reporter gene constructs. Deletion analysis of the promoter demonstrated the actions of both lithium and cocaine were mediated by the proximal promoter. Initial interrogation of ENCODE ChIP-seq data over the CACNA1C promoter indicated binding of the transcription factor ‘Enhancer of zeste homolog 2’ (EZH2), which was consistent with our data that overexpression of EZH2 repressed CACNA1C promoter reporter gene expression. Array data from the Human Brain Transcriptome demonstrated that EZH2 was highly expressed across the developing brain, but subsequently maintained at low levels after birth and adulthood. RNA-seq data obtained from PD_NGSAtlas, a reference database for epigenomic and transcriptomic data for psychiatric disorders, demonstrated a 3-fold increase in EZH2 expression in the anterior cingulate cortex of individuals with schizophrenia compared to controls. We propose that EZH2 may contribute to schizophrenia risk at two distinct time points either through disruption in development leading to neurodevelopmental changes, or through anomalous reactivation of expression in the adult brain.

Objective To compare fertility and childbearing attitudes and decisions of Portuguese and American female reproductive aged breast cancer survivors. Methods This was a cross-sectional study of 102 young breast cancer survivors (59 from Portugal and 43 from USA). Demographic, clinical and reproductive information were collected. Fertility and parenthood attitudes and decisions were assessed through a self-report questionnaire devised specifically for the study. Results Fertility issues became very important after the diagnosis for most of the women (51%). Few differences existed between USA and Portuguese participants. USA participants were more likely to undergo FP (23% USA vs Portugal 5%, p = 0.01). Portuguese women were more dissatisfied with their physician's explanations about fertility (Portugal: 23% vs USA: 3%; p = 0.01). Overall, women relied on their oncologist for fertility information (70%); only Portuguese women discussed fertility with their family medicine physician (11%). Overall, women showed positive attitudes towards motherhood. Portuguese women were more likely to report their partners placed more value on the family after their illness (Portuguese agree: 55% vs USA agree: 14%; p Conclusions Fertility and childbearing after breast cancer are important issues regardless of culture, background or country's heath care system. Overall, few differences across the USA and Portuguese samples were found on fertility and childbearing attitudes and decisions.

The Bronze Age was a period of significant socio-economic transformation that gave rise to the first complex regional polities with institutionalized inequality in Europe. Communities in southwest Transylvania, a major source of gold, copper, and salt, played a critical role in this transformation. This article examines how socio-economic changes affected how people situated settlements in resource procurement zones during the Early and Middle Bronze Age (2700–1500 cal. BCE). Taking advantage of the heterogeneous distribution of natural resources across the landscape, a GIS catchment analysis of the orientation of settlements toward particular constellations of resources is presented. Our results show increased preference for access to high quality agricultural land and access to interregional trade through the Mureș River corridor over the course of the Bronze Age. Despite the increased importance of metal within Bronze Age economies, there is no evidence that Transylvanian communities placed their settlements to maximize their ability to contest or secure access to the metal ore sources in the Apuseni Mountains. The organization of settlement systems in the Bronze Age demonstrates that Transylvanian communities prioritized socio-economic institutions beyond metal procurement. This study demonstrates that tracing how humans situate themselves in variable landscapes can provide new insights into the conditions and mechanisms of social change.

Purpose To describe the relationship between the incidence of age-related macular degeneration (AMD) and nonsteroidal anti-inflammatory drug (NSAIDs) use. Design Prospective cohort study. Methods This study consisted of participants in the California Men's Health Study. Those who completed surveys in 2002-2003 and 2006 were included. Men who self-reported use of aspirin, ibuprofen, naproxen, valdecoxib, celecoxib, and/or rofecoxib at least 3 days per week were considered NSAID users. Patients were categorized as non-users, former users, new users, or longer-term users based on survey responses. NSAID use was also categorized by type: any NSAIDs, aspirin, and/or non-aspirin NSAIDs. Age, race/ethnicity, smoking status, education, income, alcohol use, and Charlson comorbidity index score were included in the multivariate analysis as risk factors for AMD. Results A total of 51 371 men were included. Average follow-up time was 7.4 years. There were 292 (0.6%) and 1536 (3%) cases of exudative and nonexudative AMD, respectively. Longer-term use of any NSAID was associated with lower risk of exudative AMD (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.50-0.96, P = .029). New users of any NSAIDs (HR = 0.79, 95% CI 0.68-0.93, P = .0039) and aspirin (HR = 0.82, 95% CI 0.70-0.97, P = .018) had a lower risk of nonexudative AMD, although this trend did not persist in longer-term users. The relationship between exudative or nonexudative AMD and the remaining categories of NSAID use were not significant. Conclusion The overall impact of NSAIDs on AMD incidence is small; however, the lower risk of exudative AMD in longer-term NSAID users may point to a protective effect and deserves further study as a possible mechanism to modulate disease risk.

Developing fast, cost-effective assessments of wild animal abundance is an important goal for many researchers, and environmental DNA (eDNA) holds much promise for this purpose. However, the quantitative relationship between species abundance and the amount of DNA present in the environment is likely to vary substantially among taxa and with ecological context. Here, we report a strong quantitative relationship between eDNA concentration and the abundance of spawning sockeye salmon in a small stream in Alaska, USA, where we took temporally- and spatially-replicated samples during the spawning period. This high-resolution dataset suggests that (1) eDNA concentrations vary significantly day-to-day, and likely within hours, in the context of the dynamic biological event of a salmon spawning season; (2) eDNA, as detected by species-specific quantitative PCR probes, seems to be conserved over short distances (tens of meters) in running water, but degrade quickly over larger scales (ca. 1.5 km); and (3) factors other than the mere presence of live, individual fish — such as location within the stream, live/dead ratio, and water temperature — can affect the eDNA-biomass correlation in space or time. A multivariate model incorporating both biotic and abiotic variables accounted for over 75% of the eDNA variance observed, suggesting that where a system is well-characterized, it may be possible to predict species' abundance from eDNA surveys, although we underscore that species- and system-specific variables are likely to limit the generality of any given quantitative model. Nevertheless, these findings provide an important step toward quantitative applications of eDNA in conservation and management.

Objective The collection of posthumous tissue from advanced stage lung cancer patients is beneficial to medical science. Recruiting living patients to a Rapid Tissue Donation Program (RTD) poses several psychosocial challenges and little is known about perceptions of joining this type of program. This study qualitatively examined perceptions of advanced stage lung cancer patients (n = 14) participating in a lung cancer RTD program, their NoK (n = 11), and physicians (n = 6) at the Thoracic Oncology Clinic at H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida USA. Methods Semi-structured interviews were conducted with participants and interview transcripts were analyzed using the constant comparison method. Results Majority of patients joined to give back to research, discussed participation with family members, and desired for family to receive information about the use of the tissue after their death. All participating NoK were supportive of their family member’s decision. Physicians described the program as running smoothly, but provided suggestions for process improvements. Conclusion Participants joined with intention to give back to research community and families were supportive of loved one’s participation in RTD. Physicians agreed with overall process. Practice implications Key factors for a successful RTD program is tailoring to institutional and individual needs.

Anthrax lethal factor (LF) is a zinc-dependent endoprotease and a critical virulence factor for Bacillus anthracis, the causative agent of anthrax. The mass spectrometry (MS) method for total-LF quantification includes three steps; 1) LF specific antibody capture/concentration, 2) LF-specific hydrolysis of a peptide substrate, and 3) detection and quantification of LF-cleaved peptides by isotope-dilution MALDI-TOF/MS. Recombinant LF spiked plasma was used for calibration and quality control (QC) materials. Specificity was 100% from analysis of serum and plasma from 383 non-infected humans, 31 rabbits, and 24 rhesus macaques. Sensitivity was 100% from 32 human clinical anthrax cases including infections by inhalation, ingestion, cutaneous and injection exposures and experimental infections for 29 rabbits and 24 rhesus macaques with inhalation anthrax. Robustness evaluation included sample storage, serum and plasma, antimicrobial and antitoxin effects and long-term performance. Data from 100 independent runs gave detection limits 0.01 ng/mL (111 amol/mL) for the 4-h method and 0.0027 ng/mL (30 amol/mL) for an alternate 20-h method. QC precision ranged from 7.7 to 14.8% coefficient of variation and accuracy from 0.2 to 9.8% error. The validated LF MS method provides sensitive quantification of anthrax total-LF using a robust high throughput platform for early diagnosis and evaluation of therapeutics during an anthrax emergency.

Aquafeed manufacturers are increasingly interested in ensuring consistently high-quality products, while relying heavily on poultry offal meal (POM), which is inevitably variable. This study examined the chemical composition of 22 different commercially and experimentally produced POM to determine which chemical variables best predict in vivo protein digestibility in Atlantic salmon (Salmo salar) and to evaluate which production variable, rendering temperature or raw material freshness, has a greater impact on digestibility. The chemical composition of commercially and experimentally produced POM was extremely variable. Significant relationships were found between in vivo dietary protein digestibility and D-glutamic acid (R2 = 0.64) and D-aspartic acid (R2 = 0.62). Rendering temperature and raw material freshness had significant effects on D-amino acids and biogenic amines. D-glutamic and D-aspartic acids may provide rapid-assessment indication of POM quality, as these D-amino acids were linked to protein digestibility and affected by the production variables. This study supports the well-held notion that POM is subject to significant variability and addresses the specific chemical characterisation of POM and the production conditions which impact nutrient digestibility in Atlantic salmon. These results prove beneficial to aquafeed manufactures aiming to ensure consistency and high nutritional quality in protein sources for aquafeed.

Electronic Nicotine Delivery Systems, also called electronic cigarettes or e-cigarettes, have been available for over a decade and use has been increasing dramatically. The primary reported reasons for use are to aid smoking cessation or reduction, yet a significant proportion appear to be long-term users of both products (“dual users”). Dual users may be motivated to quit smoking and might benefit from a behavioral intervention for smoking cessation. This paper describes the intervention development, as well as the design, methods, and data analysis plans for an ongoing randomized controlled trial (RCT). Formative research and learner verification were conducted to create a usable, understandable, and acceptable self-help intervention targeting dual users. The efficacy is being tested in an RCT with current dual users (N=2900) recruited nationally and randomized to one of three conditions. The Assessment Only (ASSESS) group only completes assessments. The Generic Self-Help (GENERIC) group receives non-targeted smoking cessation booklets and supplemental materials sent monthly over 18 months. The e-cigarette Targeted Self-Help (eTARGET) group receives the newly developed intervention (targeted booklets and supplemental materials) sent over the same period. All participants complete self-report surveys every 3 months over 2 years. The primary study outcome is self-reported 7-day point prevalence abstinence. Cost-effectiveness metrics for the GENERIC and eTARGET interventions will also be calculated.

Background & Aims Nonrelaxing pelvic floor dysfunction (N-RPFD), or dyssynergic defecation, is the paradoxical contraction and/or impaired relaxation of pelvic floor and anal muscles during defecation. Few studies have evaluated this disorder in patients with an ileal pouch–anal anastomosis (IPAA). We investigated the frequency of N-RPFD in patients with and without chronic pouchitis following IPAA and the effectiveness of biofeedback therapy within this population. Methods We conducted a retrospective study of all patients with an IPAA who underwent anorectal manometry between January 2000 and March 2015 (n = 111). N-RPFD was diagnosed in patients with symptoms consistent with a pouch evacuation disorder and 1 or more of the following abnormal tests: anorectal manometry, balloon expulsion test, barium or magnetic resonance defecography, or external anal sphincter electromyography. Patients who completed biofeedback therapy were identified and assessed to determine symptomatic response. Results Of the 111 patients evaluated, 83 (74.8%) met criteria for N-RPFD. A significantly higher proportion of patients with chronic pouchitis were diagnosed with N-RPFD than patients without chronic pouchitis (83.3% vs 62.2%, respectively; P = .012). Most patients diagnosed with N-RPFD had abnormal results from the balloon expulsion test (78.3%); 53.0% of patients diagnosed with N-RPFD had abnormal findings from external anal sphincter electromyography, 25.3% had abnormal defecography findings, and 20.5% had abnormal findings from anorectal manometry. Twenty-two patients completed biofeedback therapy: 15 patients (68.2%) had mild–moderate improvement and 5 patients (22.7%) had significant improvement of symptoms. Conclusions N-RPFD occurs in almost 75% of patients with an IPAA, especially in patients with chronic pouchitis. Biofeedback seems to be an effective therapy for patients with an IPAA and N-RPFD, but further studies are needed for validation.

Purpose Research demonstrates a negative psychosocial impact of infertility among otherwise healthy adults, and distress among adolescents facing the prospect of future infertility due to various medical conditions and treatments that impair reproductive health. Guidelines state that providers should counsel transgender youth about potential infertility and fertility preservation (FP) options prior to initiation of hormone therapy. The purpose of this study was to examine the rates of fertility counseling and utilization of FP among a cohort of adolescents with gender dysphoria seen at a large gender clinic. Methods An Institutional Review Board–approved retrospective review of electronic medical records was conducted of all patients with ICD-9/10 codes for gender dysphoria referred to Pediatric Endocrinology for hormone therapy (puberty suppression and/or cross-sex hormones) from January 2014 to August 2016. Results Seventy-eight patients met inclusion criteria. Five children were prepubertal, no hormone therapy was considered, and they were therefore excluded. Of the remaining 73 patients, 72 had documented fertility counseling prior to initiation of hormone therapy and 2 subjects attempted FP; 45% of subjects mentioned a desire or plan to adopt, and 21% said they had never wanted to have children. Conclusions Utilization rates of FP are low among transgender adolescents. More research is needed to understand parenthood goals among transgender youth at different ages and developmental stages and to explore the impact of gender dysphoria on decision-making about FP and parenthood. Discussions about infertility risk, FP, and other family building options should be prioritized in this vulnerable adolescent population.

Signaling via the receptor tyrosine kinase CSF1R is thought to play an important role in recruitment and differentiation of tumor-associated macrophages (TAMs). TAMs play pro-tumorigenic roles, including the suppression of anti-tumor immune response, promotion of angiogenesis and tumor cell metastasis. Because of the role of this signaling pathway in the tumor microenvironment, several small molecule CSF1R kinase inhibitors are undergoing clinical evaluation for cancer therapy, either as a single agent or in combination with other cancer therapies, including immune checkpoint inhibitors. Herein we describe our lead optimization effort that resulted in the identification of a potent, cellular active and orally bioavailable bis-amide CSF1R inhibitor. Docking and biochemical analysis allowed the removal of a metabolically labile and poorly permeable methyl piperazine group from an early lead compound. Optimization led to improved metabolic stability and Caco2 permeability, which in turn resulted in good oral bioavailability in mice.

Introduction Until recently, there has not been a valid and reliable screening test for lung cancer. As compared to chest X-ray, low-dose computed tomography (LDCT) lung cancer screening has demonstrated greater sensitivity resulting in lung cancer diagnosis at an earlier stage, thereby reducing lung cancer mortality among high-risk individuals by 20%. In the current study, we sought to examine knowledge and attitudes about LDCT screening for lung cancer among an ethnically and racially diverse sample of high risk (HR) community members and primary care providers (PCP). Methods Eligible individuals participated in a focus group using semi-structured interview guides. Focus groups were conducted with PCPs (by telephone) and HRs (in-person). Sessions were audio-taped and transcribed verbatim. The constant comparison method and content analysis were used to analyze results. Results The majority of PCPs had limited knowledge of lung cancer CT screening. PCPs cited barriers to recommendation including, cost/insurance barriers and the potential for false positives. PCPs perceived the main benefit to be early detection of lung cancer. The majority of HRs had never heard of lung LDCT screening and had never had a healthcare provider recommend it to them. Perceived barriers included fear of results (bad news) and financial costs. The main perceived benefit was early detection. Conclusion Lack of knowledge about LDCT was a key a barrier across both the PCP and HR. respondents. Understanding the barriers to lung screening across diverse community populations is necessary to improve screening rates and shared decision-making.

Pre-spawning mortality (PSM) has been occasionally observed in association with high densities of adult Pacific salmon ( Oncorhynchus spp.), but because large escapements are rare, the phenomenon remains poorly understood. A large spawning escapement (∼12 times the 54 year median, and 3X the previous maximum) to a small stream in Alaska provided a unique opportunity to explore the factors that contribute to density-driven spawning ground mortality. After comparing patterns of mortality in 2014 with over 20 years of prior abundance and environmental data, we identified low dissolved oxygen (DO) as likely contributing to PSM. We then utilized a fish habitat-DO model to explore the roles of density-dependent and -independent factors in reducing DO. Stream flow and spawning density were identified as primary drivers of oxygen availability. Despite suboptimal oxygen levels the salmon did not die abruptly. Rather, on average they lived as long as in previous years (mean = 9.99 d), but many (55%) failed to complete spawning prior to death. Our results suggest that this mortality was ultimately a density-dependent process, exacerbated by low-flow conditions. Given projected effects of climate change on river flows and temperatures, similar events may occur more frequently in parts of the range of salmon where abundances remain high.