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Aims/hypothesis: Although statistical models for predicting type 1 diabetes risk have been developed, approaches that reveal the heterogeneity of the at-risk population by identifying clinically meaningful clusters are lacking. We aimed to identify and characterise clusters of islet autoantibody-positive individuals who share similar characteristics and type 1 diabetes risk. Methods: We tested a novel outcome-guided clustering method in initially non-diabetic autoantibody-positive relatives of individuals with type 1 diabetes, using the TrialNet Pathway to Prevention study data (n=1123). The outcome of the analysis was the time to development of type 1 diabetes, and variables in the model included demographic characteristics, genetics, metabolic factors and islet autoantibodies. An independent dataset (the Diabetes Prevention Trial of Type 1 Diabetes Study) (n=706) was used for validation. Results: The analysis revealed six clusters with varying type 1 diabetes risks, categorised into three groups based on the hierarchy of clusters. Group A comprised one cluster with high glucose levels (median for glucose mean AUC 9.48 mmol/l; IQR 9.16–10.02) and high risk (2-year diabetes-free survival probability 0.42; 95% CI 0.34, 0.51). Group B comprised one cluster with high IA-2A titres (median 287 DK units/ml; IQR 250–319) and elevated autoantibody titres (2-year diabetes-free survival probability 0.73; 95% CI 0.67, 0.80). Group C comprised four lower-risk clusters with lower autoantibody titres and glucose levels (with 2-year diabetes-free survival probability ranging from 0.84–0.99 in the four clusters). Within group C, the clusters exhibit variations in characteristics such as glucose levels, C-peptide levels and age. A decision rule for assigning individuals to clusters was developed. Use of the validation dataset confirmed that the clusters can identify individuals with similar characteristics. Conclusions/interpretation: Demographic, metabolic, immunological and genetic markers may be used to identify clusters of distinctive characteristics and different risks of progression to type 1 diabetes among autoantibody-positive individuals with a family history of type 1 diabetes. The results also revealed the heterogeneity in the population and complex interactions between variables. [ABSTRACT FROM AUTHOR]

Electron-ion collision spectroscopy of the KLL dielectronic recombination (DR) resonances of hydrogenlike xenon ions was performed at a heavy-ion storage ring with a resolving power that is competitive with x-ray spectroscopy of inner-shell transitions in highly charged ions. The K L 1 / 2 L 1 / 2 , K L 1 / 2 L 3 / 2 , and K L 3 / 2 L 3 / 2 resonance groups and even parts of their fine structure are individually resolved. The resonance strengths were measured on an absolute scale and compared with results from multi-configuration Dirac–Fock (MCDF) calculations. These are in excellent agreement with the experimental findings when QED effects on the resonance energies and the Breit interaction are considered. As already found for DR of hydrogenlike uranium (Bernhardt et al. in Phys Rev A 83:020701(R), 2011), this interaction is particularly strong for the K L 1 / 2 L 1 / 2 resonance group. For U 91 + , it increases the K L 1 / 2 L 1 / 2 DR resonance strength by 40%. For Xe 53 + , the increase is found to amount to 25%, confirming the prediction that the influence of the Breit interaction grows with increasing nuclear charge. A comprehensive appendix treats the derivation of experimental and theoretical merged-beams recombination rate coefficients for interacting beams of relativistic electrons and ions. [ABSTRACT FROM AUTHOR]

Excessive and improper use of antibiotics causes antimicrobial resistance which is a major threat to global health security. Hospitals in sub-Saharan Africa (SSA) has the highest prevalence of antibiotic use. This systematic review and meta-analysis aimed to determine the pooled point prevalence (PPP) of evidence-based antimicrobial use among hospitalized patients in SSA. Literature was retrieved from CINAHL, EMBASE, Google Scholar, PubMed, Scopus, and Web of Science databases. Meta-analysis was conducted using STATA version 17. Forest plots using the random-effect model were used to present the findings. The heterogeneity and publication bias were assessed using the I2 statistics and Egger's test. The protocol was registered in PROSPERO with code CRD42023404075. The review was conducted according to PRISMA guidelines. A total of 26, 272 study participants reported by twenty-eight studies published from 10 countries in SSA were included. The pooled point prevalence of antimicrobial use in SSA were 64%. The pooled estimate of hospital wards with the highest antibiotic use were intensive care unit (89%). The pooled prevalence of the most common clinical indication for antibiotic use were community acquired infection (41%). The pooled point prevalence of antimicrobial use among hospitalized patients were higher in SSA. Higher use of antibiotics was recorded in intensive care units. Community acquired infection were most common clinical case among hospitalized patients. Health systems in SSA must design innovative digital health interventions to optimize clinicians adhere to evidence-based prescribing guidelines and improve antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Purpose: We determined the proportion of cancer survivors who met each of five health behavior guidelines recommended by the American Cancer Society (ACS), including consuming fruits and vegetables at least five times/day, maintaining a body mass index (BMI) < 30 kg/m2, engaging in 150 min or more of physical activity weekly, not currently smoking, and not excessively drinking alcohol. Methods: Using data from the 2019 Behavioral Risk Factor Surveillance System (BRFSS), 42,727 survey respondents who reported a previous diagnosis of cancer (excluding skin cancer) were included. Weighted percentages with 95% confidence intervals (95% CI) were estimated for the five health behaviors accounting for BRFSS' complex survey design. Results: The weighted percentage of cancer survivors who met ACS guidelines was 15.1% (95%CI: 14.3%, 15.9%) for fruit and vegetable intake; 66.8% (95%CI: 65.9%, 67.7%) for BMI < 30 kg/m2; 51.1% (95%CI: 50.1%, 52.1%) for physical activity; 84.9% (95%CI: 84.1%, 85.7%) for not currently smoking; and 89.5% (95%CI: 88.8%, 90.3%) for not drinking excessive alcohol. Adherence to ACS guidelines among cancer survivors generally increased with increasing age, income, and education. Conclusions: While the majority of cancer survivors met the guidelines for not smoking and limiting alcohol drinking, one-third had elevated BMI, almost half did not meet recommended physical activity levels, and the majority had inadequate fruit and vegetable intake. Implications for Cancer Survivors: Adherence to guidelines was lowest among younger cancer survivors and those with lower income and education, suggesting these may be populations where resources could be targeted to have the greatest impact. [ABSTRACT FROM AUTHOR]

We prove that the ladder with 3 rungs and the house graph have the edge-Erdős–Pósa property, while ladders with 14 rungs or more have not. Additionally, we prove that the latter bound is optimal in the sense that the only known counterexample graph does not permit a better result. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the cross-sectional association between healthy dietary patterns [alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), alternative Healthy Eating Index (aHEI), and Healthy Eating Index 2015 (HEI-2015)] and urinary biomarkers of oxidative stress. Methods: Between 2003 and 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35 to 74 (non-Hispanic White, 83.7%). Data were analyzed for 844 premenopausal and 454 postmenopausal women who had urine samples analyzed for F2-isoprostanes and non-missing covariate data. Food frequency questionnaire responses were used to calculate dietary pattern scores. Concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were measured in urine samples by GC/MS for premenopausal women and LC/MS for postmenopausal women. Multivariable linear regression models were used to estimate associations between aMED, DASH, aHEI, and HEI-2015 and urinary F2-isoprostanes by menopausal status. Effect modification by sociodemographic, lifestyle, and clinical characteristics was also evaluated. Results: Among premenopausal women, the four dietary indices were inversely associated with 8-iso-PGF2α (aMED βQ4vsQ1: − 0.17, 95% CI − 0.27, − 0.08; DASH βQ4vsQ1: − 0.18, 95% CI − 0.28, − 0.08; aHEI βQ4vsQ1: − 0.20, 95% CI − 0.30, − 0.10; HEI-2015 βQ4vsQ1: − 0.19, 95% CI − 0.29, − 0.10). In contrast, inverse associations with 8-iso-PGF2α-M were found for the continuous aMED, aHEI, and HEI-2015. Associations between dietary indices and 8-iso-PGF2α were generally stronger among younger women, women with lower income, and women with higher BMI. Similar results were observed among postmenopausal women, though only the continuous DASH and aHEI models were statistically significant. Conclusion: Healthy dietary patterns were associated with lower levels of oxidative stress. [ABSTRACT FROM AUTHOR]

Rubbers reinforced with rigid particles are used in high-volume applications, including tyres, dampers, belts and hoses1. Many applications require high modulus to resist excessive deformation and high fatigue threshold to resist crack growth under cyclic load. The particles are known to greatly increase modulus but not fatigue threshold. For example, adding carbon particles to natural rubber increases its modulus by one to two orders of magnitude1–3, but its fatigue threshold, reinforced or not, has remained approximately 100 J m−2 for decades4–7. Here we amplify the fatigue threshold of particle-reinforced rubbers by multiscale stress deconcentration. We synthesize a rubber in which highly entangled long polymers strongly adhere with rigid particles. At a crack tip, stress deconcentrates across two length scales: first through polymers and then through particles. This rubber achieves a fatigue threshold of approximately 1,000 J m−2. Mounts and grippers made of this rubber bear high loads and resist crack growth over repeated operation. Multiscale stress deconcentration expands the space of materials properties, opening doors to curtailing polymer pollution and building high-performance soft machines.A rubber in which highly entangled long polymers strongly adhere with rigid particles deconcentrates stress across multiple scales, amplifying the fatigue threshold. [ABSTRACT FROM AUTHOR]

This paper deals with regularized Newton methods, a flexible class of unconstrained optimization algorithms that is competitive with line search and trust region methods and potentially combines attractive elements of both. The particular focus is on combining regularization with limited memory quasi-Newton methods by exploiting the special structure of limited memory algorithms. Global convergence of regularization methods is shown under mild assumptions and the details of regularized limited memory quasi-Newton updates are discussed including their compact representations. Numerical results using all large-scale test problems from the CUTEst collection indicate that our regularized version of L-BFGS is competitive with state-of-the-art line search and trust-region L-BFGS algorithms and previous attempts at combining L-BFGS with regularization, while potentially outperforming some of them, especially when nonmonotonicity is involved. [ABSTRACT FROM AUTHOR]

Even though it has been known for a long time that traces of perfluorinated vapors suppress gas exchange (coarsening) between the bubbles of aqueous foams, its stabilizing impact on foam coalescence has been evidenced only recently. While previous work has demonstrated this effect for different surfactant types, we investigate here the influence of the surfactant concentration. We compared the foam properties of aqueous solutions of the non-ionic surfactant dodecyldimethylphospine oxide (C12DMPO) in the absence and presence of perfluorohexane (PFH) in the gas phase. In order to decouple foam coarsening and coalescence, we accompany the foam stability experiments with (a) lifetime statistics of individual, vertical foam films pulled from the same solutions and (b) surface tension measurements in controlled gas environments. All measurements show a clear increase of foam and film stability in the presence of PFH, its effect being most pronounced above the cmc of the surfactant. The surface tension measurements show a clear co-adsorption of the PFH up to the formation of macroscopic films at saturation. We complete the analysis by showing that alkane vapors also have a stabilizing effect for the same surfactant solutions, yet much less pronounced than that of PFH. The precise origin of the stabilizing action of these hydrophobic vapors remains to be elucidated. [ABSTRACT FROM AUTHOR]

Background: Huntington's disease (HD) is a genetic, neurodegenerative disease. Due to the progressive nature of HD and the absence of a cure, (health-related) quality of life ((HR)QoL) is an important topic. Several studies have investigated (HR)QoL in HD, yet a clear synthesis of the existing literature is lacking to date. We performed a systematic review on self-reported (HR)QoL, and factors and intervention effects associated with (HR)QoL in premanifest and manifest HD gene expansion carriers (pHDGECs and mHDGECs, respectively). Methods: PubMed, EMBASE, Web of Science, and PsycINFO were searched systematically from September 17th, 2021, up to August 11th, 2022. Methodological and conceptual quality of the included studies was assessed with two appraisal tools. Results: 30 out of 70 eligible articles were included. mHDGECs experienced lower (HR)QoL compared to pHDGECs and controls, whereas mixed findings were reported when compared to other neurological diseases. Several factors were associated with (HR)QoL that might contribute to lower (HR)QoL in mHDGECs, including depressive symptoms, physical and psychological symptoms, lower functional capacity, lower support, and unmet needs. Multidisciplinary rehabilitation programs and a respiratory muscle training were beneficial for (HR)QoL in mHDGECs. Discussion: (HR)QoL is experienced differently across the course of the disease. Although (HR)QoL is key for understanding the impact of HD and the effect of symptomatic treatment, there is a need to improve the methodological and conceptual shortcomings that were found in most studies, especially regarding the conceptual clarity when reporting on QoL and HRQoL. Suggestions for strengthening these shortcomings are provided in this review. [ABSTRACT FROM AUTHOR]

Background: Naloxone is a life-saving, yet underprescribed, medication that is recommended to be provided to patients at high risk of opioid overdose. Objective: We set out to evaluate the changes in prescriber practices due to the use of an electronic health record (EHR) advisory that prompted opioid prescribers to co-prescribe naloxone when prescribing a high-dose opioid. It also provided prescribers with guidance on decreasing opioid doses for safety. Design: This was a retrospective chart abstraction study looking at all opioid prescriptions and all naloxone prescriptions written as emergency department (ED) discharge, inpatient hospital discharge, or outpatient medications, between July 1, 2018, and February 1, 2020. The EHR advisory went live on June 1, 2019. Subjects: Included in the analysis were all adult patients seen in the abovementioned settings at a large county hospital and associated outpatient clinics. Main Measures: We performed an interrupted time series analysis looking at naloxone prescriptions and daily opioid dosing in morphine milligram equivalents (MMEs), before and after initiation of the EHR advisory. Key Results: The EHR advisory was associated with changes in prescribers' behavior, leading to increased naloxone prescriptions and decreased prescribed opioid doses. Conclusions: EHR advisories are an effective systems-level intervention to enhance the safety of prescribed opioids and increase rates of naloxone prescribing. [ABSTRACT FROM AUTHOR]

T helper 9 (TH9) cells promote allergic tissue inflammation and express the type 2 cytokines, IL-9 and IL-13, as well as the transcription factor, PPAR-γ. However, the functional role of PPAR-γ in human TH9 cells remains unknown. Here, we demonstrate that PPAR-γ drives activation-induced glycolysis, which, in turn, promotes the expression of IL-9, but not IL-13, in an mTORC1-dependent manner. In vitro and ex vivo experiments show that the PPAR-γ-mTORC1-IL-9 pathway is active in TH9 cells in human skin inflammation. Additionally, we find dynamic regulation of tissue glucose levels in acute allergic skin inflammation, suggesting that in situ glucose availability is linked to distinct immunological functions in vivo. Furthermore, paracrine IL-9 induces expression of the lactate transporter, MCT1, in TH cells and promotes their aerobic glycolysis and proliferative capacity. Altogether, our findings uncover a hitherto unknown relationship between PPAR-γ-dependent glucose metabolism and pathogenic effector functions in human TH9 cells. IL-9-producing helper T (TH9) cells contribute to allergic inflammation. In this study, the authors demonstrate that the transcription factor PPAR-γ regulates TH9 effector function by promoting glucose metabolism and mTOR signaling in human allergic contact dermatitis. [ABSTRACT FROM AUTHOR]

The document is a correction notice for an article titled "Functional characterization of SLC39 family members ZIP5 and ZIP10 in overexpressing HEK293 cells reveals selective copper transport activity." The authors have decided to make the article an Open Access publication, changing the copyright to © the Author(s) 2024. The article is now distributed under the terms of the Creative Commons Attribution 4.0 International License. The document also includes information about obtaining permission for the use of third-party material. [Extracted from the article]

Background: Chronic inflammation is implicated in cancer prognosis and can be modulated by diet. We examined associations between post-diagnosis dietary inflammatory potential and mortality outcomes among post-menopausal women diagnosed with cancer in the Women's Health Initiative (WHI). Methods: Energy-adjusted dietary inflammatory index scores (E-DII) were calculated from dietary and supplemental intake data collected on the first food frequency questionnaire following the diagnosis of primary invasive cancer for 3434 women in the WHI. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for risk of death from any cause, cancer, cardiovascular disease (CVD) and other causes by post-diagnosis quartiles of E-DII. Subgroup analyses by cancer stage and grade were performed. Results: There were 1156 deaths after a median 13 years of follow-up from the date of a cancer diagnosis. In the multivariable-adjusted analyses, a more anti-inflammatory diet plus supplements after cancer diagnosis was associated with lower all-cause mortality, cancer mortality, CVD mortality and mortality from other causes with HRsQ1vs.Q4 ranging from 0.47 to 0.68 (all P-trends < 0.05). Associations were stronger for cancers diagnosed at more distant stages or moderately differentiated grades. Conclusion: A more anti-inflammatory diet plus supplements after a cancer diagnosis may improve survival for post-menopausal cancer survivors. [ABSTRACT FROM AUTHOR]

Zinc is the second most prevalent metal element present in living organisms, and control of its concentration is pivotal to physiology. The amount of zinc available to the cell cytoplasm is regulated by the activity of members of the SLC39 family, the ZIP proteins. Selectivity of ZIP transporters has been the focus of earlier studies which provided a biochemical and structural basis for the selectivity for zinc over other metals such as copper, iron, and manganese. However, several previous studies have shown how certain ZIP proteins exhibit higher selectivity for metal elements other than zinc. Sequence similarities suggest an evolutionary basis for the elemental selectivity within the ZIP family. Here, by engineering HEK293 cells to overexpress ZIP proteins, we have studied the selectivity of two phylogenetic clades of ZIP proteins, that is ZIP8/ZIP14 (previously known to be iron and manganese transporters) and ZIP5/ZIP10. By incubating ZIP over-expressing cells in presence of several divalent metals, we found that ZIP5 and ZIP10 are high affinity copper transporters with greater selectivity over other elements, revealing a novel substrate signature for the ZIP5/ZIP10 clade. [ABSTRACT FROM AUTHOR]

The Anastasia Mosquito Control District (AMCD) of St. Johns County (SJC), St. Augustine, Florida, USA, was formed in 1948 to cover the 27 km2 of Anastasia Island and control the black salt marsh mosquito, Aedes taeniorhynchus (Wiedemann). Today AMCD covers the entirety of SJC (1588 km2) and Ae. taeniorhynchus is still the most abundant mosquito species in the county. Here we present the findings from 16 years' worth of surveillance records of AMCD mosquito populations in conjunction with annual land-use land-cover (LULC) change and climate data to better understand how environmental factors have impacted SJC Ae. taeniorhynchus populations in recent history. The statistical regression and geospatial analyses demonstrated the presence of spatial and temporal clusters of Ae. taeniorhynchus populations in terms of abundance and distribution. Additionally, Ae. taeniorhynchus abundance and distribution were significantly influenced by the annual changes of LULC and climate variables. The linear regression analysis using standard least square and corrected Akaike Information Criterion revealed a migration of mangrove swamps and saltwater marshes that corresponded to a southern shift in the spatial–temporal distribution of Ae. taeniorhynchus communities. This was confirmed by the significant change in LULC characteristics between three representative years (2004, 2009, 2014) and the redistribution of Ae. taeniorhynchus abundances represented by Moran's I index values. The annual values of four climate variables (average and minimum temperature, mean dew point, and maximum vapor pressure deficit) and three LULC types (mangrove swamps, saltwater pools within saltmarshes, and upland nonforested) significantly predicted annual abundance and redistribution of Ae. taeniorhynchus. [ABSTRACT FROM AUTHOR]

Background: Cardiac dysfunction is common in the days after severe traumatic brain injury (TBI) and may contribute to hypotension episodes, leading to worse outcomes. Little is known about cardiac function in the minutes and hours immediately following TBI. By using fluid percussion TBI in a swine model, we aimed to characterize the immediate post injury cardiac function. Methods: Intubated, anesthetized immature (25.8 ± 1.5 kg) female swine were subjected to severe fluid percussion TBI (4.2 ± 0.2 atm). Beginning at 45 min, simulating hospital arrival, all animals were resuscitated with normal saline (NS), mannitol, and phenylephrine as needed to maintain a cerebral perfusion pressure more than 60 mm Hg and intracranial pressure (ICP) less than 20 mm Hg. Primary outcomes of cardiac function were cardiac output measured by thermodilution and transesophageal echo measurements of cardiac function recorded at prespecified time points and tested for trends over time using linear regression with spline at the time of resuscitation onset. Secondary outcomes included hemodynamic measurements, ICP, and cerebral perfusion pressure. Results: Eighteen animals were included. Post-TBI hemodynamic changes demonstrated an early decrease in mean arterial pressure and cerebral perfusion pressure with a corresponding increase in heart rate and ICP. Immediately after injury, there was a significant decrease in both left atrial area and tissue Doppler imaging e′ of the LV lateral wall. In addition, there was a simultaneous increase in LV end diastolic diameter and increase in E/e′ ratio of the lateral mitral annulus. All other transesophageal echo measurements demonstrated no significant changes throughout the duration of the experiment. Conclusions: Traumatic brain injury is associated with cardiac dysfunction and increased mortality, however there is still a limited understanding of the hemodynamic and echocardiographic response associated with TBI. In this study we demonstrate the hemodynamic and echocardiographic changes in the early stages of TBI in swine. The authors hope that these results may help better understanding on the management of patients with severe head injury. [ABSTRACT FROM AUTHOR]

Purpose: To examine associations between recreational and occupational physical activity and prostate cancer aggressiveness in a population-based, case-only, incident prostate cancer study. Methods: Data were analyzed from the cross-sectional North Carolina-Louisiana Prostate Cancer Project of African-American (n = 1,023) and European-American (n = 1,079) men newly diagnosed with prostate cancer (CaP). High-aggressive CaP was defined as Gleason sum ≥ 8, or prostate-specific antigen > 20 ng/ml, or Gleason sum ≥ 7 and clinical stage T3–T4. Metabolic equivalent tasks (MET) were estimated from self-reported recreational physical activity in the year prior to diagnosis assessed retrospectively via a validated questionnaire and from occupational physical activity based on job titles. Associations between physical activity variables and high-aggressive prostate cancer were estimated using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for multiple confounders. Results: There was suggestive evidence that walking for 75–150 min/week for exercise is associated with lower odds of high-aggressive prostate cancer compared to no walking (OR = 0.69, 95% CI 0.47–1.01). Physical activity at the current job was associated with 24% lower odds of high-aggressive prostate cancer (highest vs. lowest tertile OR = 0.76, 95% CI 0.56–1.04). However, total MET-h/week of recreational physical activity and accumulation of high-level physical activity at the longest-held job were not associated with high-aggressive prostate cancer. Results did not vary by race. Conclusions: The odds of high-aggressive prostate cancer were lower among men who walk for exercise and those engaged in occupations with high activity levels. [ABSTRACT FROM AUTHOR]

Purpose: We examined the associations between intake of meat and fish by preparation methods and breast cancer in the Carolina Breast Cancer Study, a racially diverse population-based case–control study. Methods: African American (AA) and European American (EA) women aged 20–74 years with a first diagnosis of invasive or in situ breast cancers were frequency matched by race and age group to controls identified through the North Carolina Division of Motor Vehicles and Medicare lists [AA: 548 cases, 452 controls; EA: 858 cases, 748 controls]. Participants self-reported meat preparation methods and intake frequencies. Adjusted odds ratios (OR) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression adjusted for age, race, alcohol intake, body mass index, family income, lactation, marital status, use of oral contraceptives, postmenopausal hormone use, smoking status, and offsets. Results: Positive associations with breast cancer were observed for intakes of grilled/barbecued hamburger (≥ once/week, OR: 1.28; 95% CI 1.01, 1.63), and pan-fried/oven-broiled beef steak (≥ once/week, OR: 1.36; 95% CI 1.08, 1.72). Inverse associations were observed for pan-fried fish (≥ once/week, OR: 0.77; 95% CI 0.60, 0.98), and for grilled/ barbecued pork chops (> 0 time/week OR: 0.81, 95% CI 0.68, 0.97). Associations tended to be stronger among EA women than among AA women. Conclusion: More frequent consumption of beef prepared with high temperature methods was associated with higher odds of breast cancer while more frequent consumption of pan-fried fish or grilled/barbecued pork chops was associated with lower odds of breast cancer. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between dietary patterns and total and obesity-related cancer risk as well as to examine if acculturation modifies this relationship. Subjects and methods: Dietary intake of postmenopausal Hispanic women (N = 5,482) enrolled in the Women's Health Initiative was estimated from a Food Frequency Questionnaire and used to calculate dietary pattern scores: Healthy Eating Index-2015 (HEI-2015), Mexican Diet (MexD) score, alternate Mediterranean Diet Score (aMED), and the energy adjusted Dietary Inflammatory Index (E-DII™). Associations were evaluated using Cox proportional hazard regression models. Results: Six hundred thirty-one cancers and 396 obesity-related cancers were diagnosed over a mean follow-up of 12 years. Across dietary scores, there were no significant associations with cancer risk or mortality. Trend analysis suggested a potentially lower risk for total cancer mortality related to the highest MexD score (HR 0.68, 95% CI 0.45–1.04, P-trend = 0.03) and lower risk for obesity-related cancer mortality related to the highest score category for MexD (HR 0.65, 95% CI 0.37–1.16, P-trend = 0.02) and aMED (HR 0.87, 95% CI 0.45–1.67, P-trend = 0.04). Further analysis suggested less acculturated women with higher MexD scores had a 56% lower risk for any cancer (HR 0.44, 95% CI 0.22–0.88, P-trend = 0.03) and 83% lower risk for cancer mortality (HR 0.17, 95% CI 0.04–0.76, P-trend = 0.01) compared to more acculturated Hispanic women. Conclusions: Dietary patterns were not associated with cancer risk and mortality in postmenopausal Hispanic women. Less acculturated, Spanish-preferred speakers who report consuming a more traditional Mexican diet may experience a lower risk of cancer and cancer mortality. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the impact of implementing community-based prostate health education programs in rural communities. Prostate cancer (PrCA) remains one of the most common cancers among men, and a growing body of literature demonstrates that large interracial differences in PrCA incidence and mortality rates consistently disfavor African Americans in comparison to European Americans. It also is evident, despite the overall decrease in cancer death rates in the USA in recent decades, rural areas are experiencing a reduction in death rates much more slowly. In this study, education session content focused on PrCA risk factors, symptoms, screening, healthy diet and exercise, treatment options, and provider communication strategies. Forty individuals participated and completed pre/post-education program surveys to assess changes in PrCA knowledge and cancer decision-making. Participants showed improvements in education and awareness following the session, and overall impressions of the program were consistently positive as exhibited by participants' answers on a satisfaction survey. The findings demonstrate the real need both in terms of research to understand the underlying problem and to provide practical solutions that can be implemented to reverse the current situation. The results obtained support community-based education programs as an effective means of delivering PrCA prevention, screening, and treatment information to rural communities. [ABSTRACT FROM AUTHOR]

Condensed phosphates may exist as linear, cyclic or branched structures. Due to their important role in nature, linear polyphosphates have been well studied. In contrast, branched phosphates (ultraphosphates) remain largely uncharacterised, because they were already described in 1950 as exceedingly unstable in the presence of water, epitomized in the antibranching-rule. This rule lacks experimental backup, since, to the best of our knowledge, no rational synthesis of defined ultraphosphates is known. Consequently, detailed studies of their chemical properties, reactivity and potential biological relevance remain elusive. Here, we introduce a general synthesis of monodisperse ultraphosphates. Hydrolysis half-lives up to days call the antibranching-rule into question. We provide evidence for the interaction of an enzyme with ultraphosphates and discover a rearrangement linearizing the branched structure. Moreover, ultraphosphate can phosphorylate nucleophiles such as amino acids and nucleosides with implications for prebiotic chemistry. Our results provide an entry point into the uncharted territory of branched condensed phosphates. The "anti-branching rule", introduced in 1950, excludes branched polyphosphates from biological relevance due to their supposedly rapid hydrolysis. Here, the authors synthesize monodisperse branched polyphosphates and demonstrate their unexpected stability in water, as well as provide evidence for their competence in phosphorylation. [ABSTRACT FROM AUTHOR]

We conducted a novel pilot randomized controlled trial of the Treatment Ambassador Program (TAP), an 8-session, peer-based, behavioral intervention for people with HIV (PWH) in South Africa not on antiretroviral therapy (ART). PWH (43 intervention, 41 controls) completed baseline, 3- and 6-month assessments. TAP was highly feasible (90% completion), with peer counselors demonstrating good intervention fidelity. Post-intervention interviews showed high acceptability of TAP and counselors, who supported autonomy, assisted with clinical navigation, and provided psychosocial support. Intention-to-treat analyses indicated increased ART initiation by 3 months in the intervention vs. control arm (12.2% [5/41] vs. 2.3% [1/43], Fisher exact p-value = 0.105; Cohen's h = 0.41). Among those previously on ART (off for > 6 months), 33.3% initiated ART by 3 months in the intervention vs. 14.3% in the control arm (Cohen's h = 0.45). Results suggest that TAP was highly acceptable and feasible among PWH not on ART. [ABSTRACT FROM AUTHOR]

Designing and implementing algorithms for medium- and large-scale quantum computers is not easy. In the previous work, we have suggested, and developed, the idea of using machine learning techniques to train a quantum system such that the desired process is "learned," thus obviating the algorithm design difficulty. This works quite well for small systems. But the goal is macroscopic physical computation. Here, we implement our learned pairwise entanglement witness on Microsoft's Q#, one of the commercially available gate model quantum computer simulators; we perform statistical analysis to determine reliability and reproducibility; and we show that after training the system in stages for an incrementing number of qubits (2, 3, 4,...) we can infer the pattern for mesoscopic N from simulation results for three-, four-, five-, six-, and seven-qubit systems. Our results suggest a fruitful pathway for general quantum computer algorithm design and for practical computation on noisy intermediate-scale quantum devices. [ABSTRACT FROM AUTHOR]

Purpose: Autoimmune diseases co-occur, perhaps due to common risk factors. The age at gluten introduction and gluten intake in early childhood has been associated with the autoimmunity preceding celiac disease (CD) and type-1 diabetes (T1D). We explored their associations with the development of thyroid autoimmunity. Methods: DAISY has prospectively followed children at increased risk for T1D and CD since 1993. During follow-up, 107 children developed thyroid autoimmunity, defined as positivity for autoantibodies against thyroid peroxidase on at least two study visits. Age at gluten introduction was ascertained from food history interviews every 3 months until 15 months of age. Gluten intake (g/day) at age 1–2 years was estimated using a food frequency questionnaire. Results: From multivariable Cox regression, there was no association between the age of gluten introduction nor the amount of gluten intake and development of thyroid autoimmunity. However, females (hazard ratio = 2.19, 95% CI: 1.46, 3.27) and cases of islet autoimmunity (HR = 2.20, 95% CI: 1.39, 3.50) were significantly more likely to develop thyroid autoimmunity, while exposure to environmental tobacco smoke decreased the risk (HR = 0.46, 95% CI: 0.30, 0.71). Conclusions: Neither the age of gluten introduction nor the amount of gluten consumed in early childhood is associated with risk of thyroid autoimmunity. [ABSTRACT FROM AUTHOR]

Advances in molecular methods and the ability to share large population-based datasets are uncovering heterogeneity within diabetes types, and some commonalities between types. Within type 1 diabetes, endotypes have been discovered based on demographic (e.g. age at diagnosis, race/ethnicity), genetic, immunological, histopathological, metabolic and/or clinical course characteristics, with implications for disease prediction, prevention, diagnosis and treatment. In type 2 diabetes, the relative contributions of insulin resistance and beta cell dysfunction are heterogeneous and relate to demographics, genetics and clinical characteristics, with substantial interaction from environmental exposures. Investigators have proposed approaches that vary from simple to complex in combining these data to identify type 2 diabetes clusters relevant to prognosis and treatment. Advances in pharmacogenetics and pharmacodynamics are also improving treatment. Monogenic diabetes is a prime example of how understanding heterogeneity within diabetes types can lead to precision medicine, since phenotype and treatment are affected by which gene is mutated. Heterogeneity also blurs the classic distinctions between diabetes types, and has led to the definition of additional categories, such as latent autoimmune diabetes in adults, type 1.5 diabetes and ketosis-prone diabetes. Furthermore, monogenic diabetes shares many features with type 1 and type 2 diabetes, which make diagnosis difficult. These challenges to the current classification framework in adult and paediatric diabetes require new approaches. The 'palette model' and the 'threshold hypothesis' can be combined to help explain the heterogeneity within and between diabetes types. Leveraging such approaches for therapeutic benefit will be an important next step for precision medicine in diabetes. [ABSTRACT FROM AUTHOR]

The objectives of the study were to compare the cephalad migration of two patient positioning pads used in robotic gynecologic surgery and to determine if any correlation exists between cephalad movement and time in Trendelenburg position or body mass index. This was a prospective randomized controlled open-label trial (Canadian Task Force classification I). Sixty women undergoing robotic-assisted laparoscopic gynecologic surgery were randomized to the Pink Pad® system or egg-crate foam pre-operatively. Patients were placed under general anesthesia and then positioned in dorsal lithotomy. The locations of the iliac crest, acromion process, and buttock were marked on the table before and after surgery to calculate cephalad migration during surgery. The primary outcome was centimeters of cephalad migration at the three anatomic landmarks. Comparing the Pink Pad® (n = 24) to the egg-crate group (n = 26) revealed similar mean cephalad migration at the iliac crest (4.8 cm vs 4.3 cm, p = 0.56) and the shoulder (4.6 cm vs 3.9 cm, p = 0.39), and less cephalad migration at the buttock (median 3.0 cm vs 2.0 cm, p = 0.041). The total time in Trendelenburg was not correlated with cephalad migration at any anatomic landmark. Body mass index was positively correlated with cephalad migration only at the iliac crest (p = 0.032) regardless of pad type. The egg-crate foam resulted in less cephalad migration at all anatomic sites and significantly less migration at the buttocks compared to the Pink Pad®. This suggests that the less-costly egg-crate foam is noninferior to the Pink Pad® system and trends at superiority. [ABSTRACT FROM AUTHOR]

Purpose: Dietary factors may influence colorectal cancer (CRC) survival through effects on inflammation. We examined the association between post-CRC diagnosis inflammatory potential of diet and all-cause and cancer-specific mortality in the Women's Health Initiative. Methods: The study included 463 postmenopausal women who developed CRC during follow-up and completed a food frequency questionnaire (FFQ), on average 1.7 years after diagnosis. Women were followed from CRC diagnosis until death, censoring, or the end of follow-up in October 2014. Energy-adjusted dietary inflammatory index (E-DII)® scores were calculated from the FFQ and dietary supplement inventory. Cox proportional hazards models were fitted to estimate multivariable-adjusted HRs and 95% confidence intervals (CIs) for all-cause, total cancer, and CRC-specific mortality with the most pro-inflammatory E-DII scores (tertile 3) as referent. Results: After a median 11.6 years of follow-up, 162 deaths occurred, including 77 from CRC. Lowest tertile (i.e., most anti-inflammatory) E-DII scores from diet plus supplements were associated with significantly lower all-cause mortality (HRT1vsT3 = 0.49; 95% CI 0.31–0.79) compared to the most pro-inflammatory E-DII tertile. Modest associations with total cancer mortality or CRC-specific mortality were observed, though 95% CIs included 1. Conclusions: Consuming a dietary pattern and supplements with more anti-inflammatory potential after CRC diagnosis may improve overall survival among postmenopausal women. [ABSTRACT FROM AUTHOR]

Purpose Of Review: About 50% of the heritability of type 1 diabetes (T1D) is attributed to human leukocyte antigen (HLA) alleles and the remainder to several (close to 50) non-HLA loci. A current challenge in the field of the genetics of T1D is to apply the knowledge accumulated in the last 40 years towards differential diagnosis and risk assessment.Recent Findings: T1D genetic risk scores seek to combine the information from HLA and non-HLA alleles to improve the accuracy of diagnosis, prediction, and prognosis. Here, we describe genetic risk scores that have been developed and validated in various settings and populations. Several genetic scores have been proposed that merge disease risk information from multiple genetic factors to optimize the use of genetic information and ultimately improve prediction and diagnosis of T1D. [ABSTRACT FROM AUTHOR]

The Lepontine gneiss dome represents a unique region of the Central Alps where Oligocene–Miocene amphibolite facies grade rocks and fold nappes of the deepest tectonic level of the Alpine orogenic belt are exposed in a tectonic window. The Cenozoic structures of the Maggia nappe reveals a giant tens of kilometre-scale tubular fold structure that cross-cut through the surrounding lower Penninic nappes from its root situated in the southern steep-belt of the Alps near Bellinzona. The Mesozoic sedimentary cover of the Maggia nappe is typical for the Helvetic stratigraphic domain. The age of formation of the lower Penninic fold-nappes by ductile detachment of the upper European crust during its underthrusting below the higher Penninic and Austroalpine orogenic lid and Adriatic indenter was estimated between 40 and 30 Ma. Maximal pressures of 8–9 kbars and temperatures of 600–700 °C were attended during and after the nappe emplacement some 30–22 Ma ago. The Maggia and surrounding nappes are crosscut by the isograds of the Barrovian regional metamorphism. [ABSTRACT FROM AUTHOR]

This paper deals with a class of cone-reducible constrained optimization problems which encompasses nonlinear programming, semidefinite programming, second-order cone programming, and any combination thereof. Using the second-order sufficient condition and a strict version of the Robinson constraint qualification, we provide a (semi-)local error bound which generalizes known results from the literature. Moreover, under the same assumptions, we prove that an augmented Lagrangian method is locally convergent with rate proportional to 1 / ρ k , where ρ k is the penalty parameter, and that { ρ k } remains bounded. [ABSTRACT FROM AUTHOR]