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Little is known regarding the relationship between common comorbidities in persons with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) and post-TB mortality. We conducted a retrospective cohort study among persons who initiated treatment for rifampicin-resistant or multi/extensively drug-resistant (RR or M/XDR) TB reported to the country of Georgia's TB surveillance during 2009–2017. Exposures included HIV serologic status, diabetes, and HCV status. Our outcome was all-cause post-TB mortality determined by cross-validating vital status with Georgia's death registry through November 2019. We estimated adjusted hazard rate ratios (aHR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without comorbidities using cause-specific hazard regressions. Among 1032 eligible participants, 34 (3.3%) died during treatment and 87 (8.7%) died post-TB treatment. The median time to post-TB death was 21 months (interquartile range 7–39) after TB treatment. After adjusting for confounders, the hazard rates of post-TB mortality were higher among participants with HIV co-infection (aHR = 3.74, 95%CI 1.77–7.91) compared to those without HIV co-infection. In our cohort, post-TB mortality occurred most commonly in the first 3 years post-TB treatment. Linkage to care for common TB comorbidities post-treatment may reduce post-TB mortality rates. [ABSTRACT FROM AUTHOR]

Lasiosiphon Fresen. (Thymelaeaceae: Thymelaeoideae) is now understood to be a morphologically diverse genus distributed across southern and tropical Africa, Madagascar, and India. It is diagnosed morphologically by ± involucrate, mostly pedunculate heads of pentamerous or tetramerous flowers, with or without petaloid scales, and a bright yellow, orange, or red corolla. The taxonomic history of Lasiosiphon has been marked by several revisions in its circumscription and status, particularly regarding its relationship with Gnidia L. Our phylogenetic analysis of nuclear (ITS) and plastid (matK, rbcL, rps16 and trnL-F) regions of an expanded sampling of the tropical African species of Gnidia provides compelling supporting evidence for existing morphological evidence to include all the tropical African species of Gnidia in Lasiosiphon. We accordingly provide 31 new combinations in Lasiosiphon for species of Gnidia that currently lack combinations in that genus. We also provide a comprehensive nomenclator of all currently recognized Lasiosiphon species at the regional level encompassing their distribution across different geographic regions globally. This will serve as the framework for future taxonomic revisions in the genus. [ABSTRACT FROM AUTHOR]

Purpose: Incisional hernia (IH) is a common complication following abdominal surgery. Surgical repair of IH is associated with the alleviation of symptoms and improvement of quality of life. Operative intervention can pose a significant burden to the patient and healthcare facilities. This study aims to describe and compare outcomes of elective and emergency surgical repair of IH. Methods: This study is a single-centre comparative retrospective study including patients who had repair of IH. Patients were divided into Group I (Emergency) and Group II (Elective), and a comparison was conducted between them. Results: Two hundred sixty-two patients were identified with a mean age of 61.8 ± 14.2 years, of which 152 (58%) were females. The mean BMI was 31.6 ± 7.2 kg/m2. More than 58% had at least one comorbidity. 169 (64.5%) patients had an elective repair, and 93 (35.5%) had an emergency repair. Patients undergoing emergency repair were significantly older and had higher BMI, p = 0.031 and p = 0.002, respectively. The significant complication rate (Clavien–Dindo III and IV) was 9.54%. 30 and 90-day mortality rates were 2.3% (n = 6) and 2.68% (n = 7), respectively. In the emergency group, the overall complications, 30-day and 90-day mortality rates were significantly higher than in the elective group, p ≤ 0.001, 0.002 and 0.001, respectively. Overall, 42 (16.1%) developed wound complications, 25 (9.6%) experienced a recurrence, and 41 (15.71%) were readmitted within 90 days, without significant differences between the two groups. Conclusion: Patients who underwent emergency repair were significantly older and had a higher BMI than the elective cases. Emergency IH repair is associated with higher complication rates and mortality than elective repair. [ABSTRACT FROM AUTHOR]

Background: Multi-disciplinary Meetings (MDM) play a crucial role in complex patient care, involving input from various specialties to formulate evidence-based management plans. However, traditional unidirectional approaches and reliance on manual processes have led to inefficiencies in the MDM pathway. Aims: This study identified and aimed to improve four critical moments where Information Communication Technologies (ICTs) could enhance the MDM process. Initial referral, information synthesis, meeting presentation and the creation of actionable/auditable items. Methods: Microsoft Office Forms, a customisable survey platform, was implemented to streamline MDM processes. Forms were created to gather patient information, develop agendas, and track outcomes. Automation through Excel scripting further optimised data organisation and agenda creation. Results: Referrals using Forms takes an average of 7 min and 21 s. Over 15 months the submission time has reduced and is trending towards under 5 min for each referral. The system's scalability has allowed 1744 cases to be discussed over a 15-month period. Active departments using Forms is expanding to seven from two prior to the pilot. Conclusion(s): Microsoft Office Forms proved to be a valuable and adaptable tool for MDMs, offering benefits such as streamlined information gathering, real-time collaboration, and scalability. The study highlights the potential of existing tools within Microsoft licenses for healthcare process optimisation, providing a cost-effective and customisable solution for MDM agendas. While recognising some limitations, the study concludes that leveraging Microsoft Office Forms can significantly improve system efficiency in a multi-disciplinary setting. [ABSTRACT FROM AUTHOR]

This article examines the use of a standardized set of outcomes, known as a Core Outcome Set (COS), in clinical trials for anxiety disorders. The study found that there was a decrease in reporting of outcome measures before the publication of the COS, but no significant change after. The most commonly measured outcomes were 'symptom burden' and 'functioning', while 'medication side effects' and 'absenteeism' were less frequently measured. The study also found that the continent and funding type of the trials had an impact on outcome measurement, with trials from Australia and those funded by industry reporting the highest percentage of COS outcomes. The lack of adherence to the COS leads to inconsistent outcomes across trials, making it difficult to compare treatments and make clinical decisions. Further research is needed to identify barriers to adherence and increase awareness of the importance of the COS. [Extracted from the article]

Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats. Psilocin increased stimulus-independent PVN activity as measured by c-Fos expression in male and female rats. Psilocin increased PVN reactivity to an aversive air-puff stimulus in males but not females. Reactivity was restored at 2- and 7-days post-injection with no group differences. Additionally, prior psilocin injection did not affect PVN reactivity following acute restraint stress. Experimental groups sub-classified by baseline threat responding indicate that increased male PVN reactivity is driven by active threat responders. These findings identify the PVN as a significant site of psychedelic drug action with implications for threat responding behavior. The neurobiological mechanisms underlying the fast acting and long-lasting effects of these drugs are not fully understood. Here authors show that the psychedelic psilocin increases reactivity in the paraventricular nucleus of the hypothalamus (PVN) in male rats but does not change acute stress response. Male reactivity changes are driven by active threat responding, with clinical implications. [ABSTRACT FROM AUTHOR]

The interplay of positive and negative species interactions controls species assembly in communities. Dryland plant communities, such as savannas, are important to global biodiversity and ecosystem functioning. Sandhill oaks in xeric savannas of the southeastern United States can facilitate longleaf pine by enhancing seedling survival, but the effects of oaks on recruitment and growth of longleaf pine have not been examined. We censused, mapped, and monitored nine contiguous hectares of longleaf pine in a xeric savanna to quantify oak-pine facilitation, and to examine other factors impacting recruitment, such as vegetation cover and longleaf pine tree density. We found that newly recruited seedlings and grass stage longleaf pines were more abundant in oak-dominated areas where densities were 230% (newly recruited seedlings) and 360% (grass stage) greater from lowest to highest oak neighborhood densities. Longleaf pine also grew faster under higher oak density. Longleaf pine recruitment was lowest under longleaf pine canopies. Mortality of grass stage and bolt stage longleaf pine was low (~1.0% yr−1) in the census interval without fire. Overall, our findings highlight the complex interactions between pines and oaks—two economically and ecologically important genera globally. Xeric oaks should be incorporated as a management option for conservation and restoration of longleaf pine ecosystems. [ABSTRACT FROM AUTHOR]

Abstract A subset of lung adenocarcinomas is driven by the EML4‐ALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to on‐target mutations or parallel pathway alterations is a major clinical challenge. Exploring these mechanisms of resistance, we found that EML4‐ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib. These compounds robustly induce apoptosis through transcriptional inhibition and downregulation of anti‐apoptotic genes. Importantly, alvocidib reduced tumour progression in xenograft mouse models. In summary, our study takes advantage of the transcriptional addiction hypothesis to propose a new treatment strategy for a subset of patients with acquired resistance to first‐, second‐ and third‐generation ALK inhibitors.

Even though Artificial Intelligence (AI) has been having a transformative effect on human life, there is currently no precise quantitative method for measuring and comparing the performance of different AI methods. Technology Improvement Rate (TIR) is a measure that describes a technology's rate of performance improvement, and is represented in a generalization of Moore's Law. Estimating TIR is important for R&D purposes to forecast which competing technologies have a higher chance of success in the future. The present contribution estimates the TIR for different subdomains of applied and industrial AI by quantifying each subdomain's centrality in the global flow of technology, as modeled by the Patent Citation Network and shown in previous work. The estimated TIR enables us to quantify and compare the performance improvement of different AI methods. We also discuss the influencing factors behind slower or faster improvement rates. Our results highlight the importance of Rule-based Machine Learning (not to be confused with Rule-based Systems), Multi-task Learning, Meta-Learning, and Knowledge Representation in the future advancement of AI and particularly in Deep Learning. [ABSTRACT FROM AUTHOR]

Background: Since the coronavirus disease 2019 (COVID-19) pandemic began, telemedicine use has transformed healthcare delivery. Yet there is concern that telemedicine may widen care disparities for vulnerable populations, and patient experience data are limited. Aims: We aimed to assess patient satisfaction with hepatology-related telemedicine (telehepatology) for delivery of fatty liver disease (FLD) care in a safety-net healthcare system. Methods: Adult patients with FLD were surveyed regarding satisfaction with telehepatology. Clinical, demographic, resources, and social determinants of health (SDoH) data were collected to identify factors associated with satisfaction through multivariable modeling. Results: From June 2020 to March 2022, 220 participants were enrolled: the median age was 52 years, 37% were men, and 68% were Hispanic. One hundred nineteen (54%) had prior telehepatology experience. Overall, satisfaction was high; 70% reported being somewhat or very satisfied. On univariate analysis, Hispanic ethnicity (versus non-Hispanic, OR 0.34, 95% CI 0.1–0.9, p = 0.03) and limited access to personal cellphone/internet (OR 0.16, 95% CI 0.04–0.6, p = 0.01) were associated with lower satisfaction. On multivariable logistic regression modeling adjusted for pandemic duration, age, sex, severity of liver disease, and coexisting liver disease, Hispanic ethnicity and lack of personal cellphone/internet remained independently associated with lower telehepatology satisfaction (OR 0.24, 95% CI 0.07–0.9, p = 0.03 and OR 0.2, 95% CI 0.04–0.9, p = 0.04, respectively). The association remained statistically significant after inclusion of various SDoH in the multivariable model. Conclusions: Satisfaction with telehepatology among FLD patients in a safety-net clinical setting was high overall. However, Hispanic ethnicity and lack of personal cellphone/internet were independently associated with lower telehepatology satisfaction. A better understanding of patients' experience with telehepatology is needed to identify reasons for dissatisfaction, and in-person visits should remain an option for patients to ensure equitable care. [ABSTRACT FROM AUTHOR]

Let w be a word in the free group on r generators. The expected value of the trace of the word in r independent Haar elements of O (n) gives a function T r w O (n) of n. We show that T r w O (n) has a convergent Laurent expansion at n = ∞ involving maps on surfaces and L 2 -Euler characteristics of mapping class groups associated to these maps. This can be compared to known, by now classical, results for the GUE and GOE ensembles, and is similar to previous results concerning U n , yet with some surprising twists. A priori to our result, T r w O (n) does not change if w is replaced with α (w) where α is an automorphism of the free group. One main feature of the Laurent expansion we obtain is that its coefficients respect this symmetry under Aut (F r) . As corollaries of our main theorem, we obtain a quantitative estimate on the rate of decay of T r w O (n) as n → ∞ , we generalize a formula of Frobenius and Schur, and we obtain a universality result on random orthogonal matrices sampled according to words in free groups, generalizing a theorem of Diaconis and Shahshahani. Our results are obtained more generally for a tuple of words w 1 , ... , w ℓ , leading to functions T r w 1 , ... , w ℓ O . We also obtain all the analogous results for the compact symplectic groups Sp (n) through a rather mysterious duality formula. [ABSTRACT FROM AUTHOR]

This article discusses a rare genetic deficiency called C5 deficiency, which predisposes individuals to recurrent infections with Neisseria species. The article presents a case study of a 22-year-old male who had both Neisseria meningitis and diffuse cutaneous HSV-1 infection and was found to have two novel mutations in the C5 gene. The study identifies the specific variants and discusses their potential impact on the function of the C5 protein. The article also explores the association between C5 deficiency and HSV-1 infection, suggesting a potential mechanism for immune evasion by the virus. The authors conclude that C5 deficiency should be considered in patients with Neisseria meningitis, and further research is needed to understand the association with HSV-1 infection. [Extracted from the article]

Fock and Goncharov described a quantization of cluster X -varieties (also known as cluster Poisson varieties) in Fock and Goncharov (Ann. Sci. Éc. Norm. Supér. 42(6), 865–930 2009). Meanwhile, families of deformations of cluster X -varieties were introduced in Bossinger et al. (Compos. Math. 156(10), 2149–2206, 2020). In this paper we show that the two constructions are compatible– we extend the Fock-Goncharov quantization of X -varieties to the families of Bossinger et al. (Compos. Math. 156(10), 2149–2206, 2020). As a corollary, we obtain that these families and each of their fibers have Poisson structures. We relate this construction to the Berenstein-Zelevinsky quantization of A -varieties (Berenstein and Zelevinsky, Adv. Math. 195(2), 405–455, 2005). Finally, inspired by the counter-example to quantum positivity of the quantum greedy basis in Lee, et al. (Proc. Natl. Acad. Sci. 111(27), 9712–9716, 2014), we compute a counter-example to quantum positivity of the quantum theta basis. [ABSTRACT FROM AUTHOR]

Purpose: People living with cystic fibrosis (CF) experience impaired quality of life, but the extent to which pulmonary function is associated with quality of life in CF remains unclear Methods: Using baseline data from a trial of specialist palliative care in adults with CF, we examined the association between pulmonary obstruction and quality of life (measured with the Functional Assessment of Chronic Illness Therapy Total Score). Results: Among 262 participants, median age was 33, and 78% were on modulator therapy. The median quality of life score was higher in those with mild obstruction (135, IQR 110–156) compared to moderate (125, IQR 109–146) and severe obstruction (120, IQR 106–136). In an unadjusted model, we observed a non-significant trend toward lower quality of life with increased obstruction—compared to participants with mild obstruction, those with moderate obstruction had quality of life score 7.46 points lower (95% CI -15.03 to 0.10) and those with severe obstruction had a score 9.98 points lower (95% CI -21.76 to 1.80). However, this association was no longer statistically significant in the adjusted model, which may reflect confounding due to sex, age, BMI, and modulator therapy. Comorbidities (depression and anxiety) and social determinants of health (financial insecurity and education) were also associated with quality of life. Conclusion: Advancing our understanding of patient-centered markers of quality of life, rather than focusing on pulmonary function alone, may help identify novel interventions to improve quality of life in this patient population. [ABSTRACT FROM AUTHOR]

Coastal dune systems in northwest Europe are facing conflicting challenges associated with climate change and human interventions in landuse and landscape management. Research over the last decade has highlighted a global stabilisation pattern in coastal dunes, fuelling long-standing debates surrounding conservation approaches. Dune erosion can be considered an important process within a naturally functioning dune system, but also a management challenge. The fossorial behaviour of burrowing mammals within coastal dunes is one driver of erosion that has long tested our perspectives on natural processes within dunes, but is understudied in coastal dune conservation and research. This is particularly the case for the wild European rabbit, a common naturalised invader of dune systems. In this study, the spatial distribution of wild European rabbits inhabiting a coastal dune system in Ireland is explored through geospatial mapping approaches using satellite and drone imagery, supported by spatial analyses and statistics. This reproducible approach has shown that rabbit activity fluctuates at inter-annual time scales that infer aligned changes in population, and that burrows clearly cluster in fixed dune habitats on landward slopes toward the rear of the dune system. [ABSTRACT FROM AUTHOR]

Integrative data analysis (IDA) was used to derive developmental models of depression, externalizing problems, and self-regulatory processes in three prevention trials of the Family Check-Up and one longitudinal, community-based study of girls over a 10-year span covering early to late adolescence (N = 4,773; 74.9% female, 41.7% white). We used moderated nonlinear factor analysis to create harmonized scores based on all available items for a given participant in the pooled dataset while accounting for potential differences in both the latent factor and the individual items as a function of observed covariates. We also conducted latent growth model analyses to examine developmental trajectories of risk. Results indicated a bidirectional relationship between depression and externalizing problems, with greater baseline externalizing problems and depression predicting growth in inhibitory control difficulties. Furthermore, initial level of inhibitory control difficulties was associated with growth in depression. We did not, however, find a relationship between early inhibitory control difficulties and growth in externalizing problems. This work illustrates the utility of IDA techniques to harmonize data across multiple studies to identify risk factors for the development of depression and externalizing problems that can be targeted by prevention efforts. [ABSTRACT FROM AUTHOR]

Background: The status of regional tumour draining lymph nodes (LN) is crucial for prognostic evaluation in gastric cancer (GaC) patients. Changes in lymph node microarchitecture, such as follicular hyperplasia (FH), sinus histiocytosis (SH), or paracortical hyperplasia (PH), may be triggered by the anti-tumour immune response. However, the prognostic value of these changes in GaC patients is unclear. Methods: A systematic search in multiple databases was conducted to identify studies on the prognostic value of microarchitecture changes in regional tumour-negative and tumour-positive LNs measured on histopathological slides. Since the number of GaC publications was very limited, the search was subsequently expanded to include junctional and oesophageal cancer (OeC). Results: A total of 28 articles (17 gastric cancer, 11 oesophageal cancer) met the inclusion criteria, analyzing 26,503 lymph nodes from 3711 GaC and 1912 OeC patients. The studies described eight different types of lymph node microarchitecture changes, categorized into three patterns: hyperplasia (SH, FH, PH), cell-specific infiltration (dendritic cells, T cells, neutrophils, macrophages), and differential gene expression. Meta-analysis of five GaC studies showed a positive association between SH in tumour-negative lymph nodes and better 5-year overall survival. Pooled risk ratios for all LNs showed increased 5-year overall survival for the presence of SH and PH. Conclusions: This systematic review suggests that sinus histiocytosis and paracortical hyperplasia in regional tumour-negative lymph nodes may provide additional prognostic information for gastric and oesophageal cancer patients. Further studies are needed to better understand the lymph node reaction patterns and explore their impact of chemotherapy treatment and immunotherapy efficacy. [ABSTRACT FROM AUTHOR]

The increasing demand for fertility treatments has led to the rise of private clinics offering complementary and alternative medicine (CAM) treatments. The most frequently offered CAM infertility treatment is acupuncture. However, there is no good evidence to support the effectiveness of acupuncture in treating infertility. This study evaluates the scope of information provided by CAM fertility clinics in the UK. A content analysis was conducted on 200 websites of CAM fertility clinics in the UK that offer acupuncture as a treatment for infertility. Of the 48 clinics that met the eligibility criteria, the majority of the websites did not provide sufficient information on the efficacy, risks and success rates of acupuncture for infertility. This has the potential to infringe on patient autonomy, provide false hope and reduce the chances of pregnancy ever being achieved as fertility declines during the time course of ineffective acupuncture treatment. [ABSTRACT FROM AUTHOR]

Background: Large-river decision-makers are charged with maintaining diverse ecosystem services through unprecedented social-ecological transformations as climate change and other global stressors intensify. The interconnected, dendritic habitats of rivers, which often demarcate jurisdictional boundaries, generate complex management challenges. Here, we explore how the Resist–Accept–Direct (RAD) framework may enhance large-river management by promoting coordinated and deliberate responses to social-ecological trajectories of change. The RAD framework identifies the full decision space of potential management approaches, wherein managers may resist change to maintain historical conditions, accept change toward different conditions, or direct change to a specified future with novel conditions. In the Upper Mississippi River System, managers are facing social-ecological transformations from more frequent and extreme high-water events. We illustrate how RAD-informed basin-, reach-, and site-scale decisions could: (1) provide cross-spatial scale framing; (2) open the entire decision space of potential management approaches; and (3) enhance coordinated inter-jurisdictional management in response to the trajectory of the Upper Mississippi River hydrograph. Results: The RAD framework helps identify plausible long-term trajectories in different reaches (or subbasins) of the river and how the associated social-ecological transformations could be managed by altering site-scale conditions. Strategic reach-scale objectives may reprioritize how, where, and when site conditions could be altered to contribute to the basin goal, given the basin's plausible trajectories of change (e.g., by coordinating action across sites to alter habitat connectivity, diversity, and redundancy in the river mosaic). Conclusions: When faced with long-term systemic transformations (e.g., > 50 years), the RAD framework helps explicitly consider whether or when the basin vision or goals may no longer be achievable, and direct options may open yet unconsidered potential for the basin. Embedding the RAD framework in hierarchical decision-making clarifies that the selection of actions in space and time should be derived from basin-wide goals and reach-scale objectives to ensure that site-scale actions contribute effectively to the larger river habitat mosaic. Embedding the RAD framework in large-river decisions can provide the necessary conduit to link flexibility and innovation at the site scale with stability at larger scales for adaptive governance of changing social-ecological systems. [ABSTRACT FROM AUTHOR]

Background: Pediatric radiologists can identify a liver ultrasound (US) pattern predictive of progression to advanced liver disease. However, reliably discriminating these US patterns remains difficult. Quantitative magnetic resonance imaging (MRI) may provide an objective measure of liver disease in cystic fibrosis (CF). Objective: The purpose of this study was to determine if quantitative MRI, including MR elastography, is feasible in children with CF and to determine how quantitative MRI-derived metrics compared to a research US. Materials and methods: A prospective, multi-institutional trial was performed evaluating CF participants who underwent a standardized MRI. At central review, liver stiffness, fat fraction, liver volume, and spleen volume were obtained. Participants whose MRI was performed within 1 year of US were classified by US pattern as normal, homogeneous hyperechoic, heterogeneous, or nodular. Each MRI measure was compared among US grade groups using the Kruskal–Wallis test. Results: Ninety-three participants (51 females [54.8%]; mean 15.6 years [range 8.1–21.7 years]) underwent MRI. MR elastography was feasible in 87 participants (93.5%). Fifty-eight participants had an US within 1 year of MRI. In these participants, a nodular liver had significantly higher stiffness (P<0.01) than normal or homogeneous hyperechoic livers. Participants with a homogeneous hyperechoic liver had a higher fat fraction (P<0.005) than others. Conclusion: MR elastography is feasible in children with CF. Participants with a nodular pattern had higher liver stiffness supporting the US determination of advanced liver disease. Participants with a homogeneous hyperechoic pattern had higher fat fractions supporting the diagnosis of steatosis. [ABSTRACT FROM AUTHOR]

A finite group G is called C-quasirandom (by Gowers) if all non-trivial irreducible complex representations of G have dimension at least C. For any unit ℓ 2 function on a finite group we associate the quantum probability measure on the group given by the absolute value squared of the function. We show that if a group is highly quasirandom, in the above sense, then any Cayley graph of this group has an orthonormal eigenbasis of the adjacency operator such that the quantum probability measures of the eigenfunctions put close to the correct proportion of their mass on suitably selected subsets of the group that are not too small. [ABSTRACT FROM AUTHOR]

Tropical cyclones (TCs) impact the economy, properties, lives and infrastructure of island nations and territories of the southwest Pacific (SWP), accounting for three in four regional disasters each year. To increase the resilience of the SWP to the destructive impacts of TCs, improved TC track forecasts are needed since a high degree of uncertainty exists around the likely path a TC will take in this region post-formation. This requires better comprehension of the factors contributing to TC track variability occurring at different timescales. Therefore, we examine the modulating impact of key Indo-Pacific climate drivers: the El Niño-Southern Oscillation (ENSO), Interdecadal Pacific Oscillation (IPO), Southern Annular Mode (SAM) and the Indian Ocean Dipole (IOD), on SWP TC track variability. We present new insights into the spatial (i.e. prevailing trajectories) and temporal (i.e. track length, average speed and duration) components of TC tracks, being modulated by both individual and combined climate modes. Overall, TC tracks tend to shift northeast during El Niño, IPO positive, IOD east positive and/or SAM negative phases (with a southwest shift observed during the opposite climate phases). Further, we show that when two of these climate modes are in their positive phase (e.g. El Niño with the positive phases of IPO or eastern pole of IOD and SAM), TC track length and average speed are enhanced. However, for cases where either one (e.g. El Niño/negative phase of IPO and IOD east) or two (La Niña/negative phase of IPO, IOD east and SAM) climate modes were in the negative phase, an increase in TC track duration was observed. The findings of this study may be used to improve TC forecasting and better quantify TC-related risks. [ABSTRACT FROM AUTHOR]

The zoonotic origin of the COVID-19 pandemic virus highlights the need to fill the vast gaps in our knowledge of SARS-CoV-2 ecology and evolution in non-human hosts. Here, we detected that SARS-CoV-2 was introduced from humans into white-tailed deer more than 30 times in Ohio, USA during November 2021-March 2022. Subsequently, deer-to-deer transmission persisted for 2–8 months, disseminating across hundreds of kilometers. Newly developed Bayesian phylogenetic methods quantified how SARS-CoV-2 evolution is not only three-times faster in white-tailed deer compared to the rate observed in humans but also driven by different mutational biases and selection pressures. The long-term effect of this accelerated evolutionary rate remains to be seen as no critical phenotypic changes were observed in our animal models using white-tailed deer origin viruses. Still, SARS-CoV-2 has transmitted in white-tailed deer populations for a relatively short duration, and the risk of future changes may have serious consequences for humans and livestock. White-tailed deer are an important reservoir of SARS-CoV-2 in the USA and continued monitoring of the virus in deer populations is needed. In this genomic epidemiology study from Ohio, the authors show that the virus has been introduced multiple times to deer from humans, and that it has evolved faster in deer. [ABSTRACT FROM AUTHOR]

The treatment strategy required for the effective healing of diabetic foot ulcer (DFU) is a complex process that is requiring several combined therapeutic approaches. As a result, there is a significant clinical and economic burden associated in treating DFU. Furthermore, these treatments are often unsuccessful, commonly resulting in lower-limb amputation. The use of drug-loaded scaffolds to treat DFU has previously been investigated using electrospinning and fused deposition modelling (FDM) 3D printing techniques; however, the rapidly evolving field of bioprinting is creating new opportunities for innovation within this research area. In this study, 3D-bioprinted scaffolds with different designs have been fabricated for the delivery of an antibiotic (levoflocixin) to DFU. The scaffolds were fully characterised by a variety of techniques (e.g. SEM, DSC/TGA, FTIR, and mechanical characterisation), demonstrating excellent mechanical properties and providing sustained drug release for 4 weeks. This proof of concept study demonstrates the innovative potential of bioprinting technologies in fabrication of antibiotic scaffolds for the treatment of DFU. [ABSTRACT FROM AUTHOR]

Introduction: We describe celiac disease epidemiology in the US military population. Methods: This is a population-based study from data collected between 2000 and 2021. Incidence and prevalence rates and descriptive statistics for demographics are presented. Results: Overall, 2248 incident cases of celiac disease were identified. The incidence rate increased from 1.2 to 14.0 per 100,000 person-years and the overall lifetime prevalence increased from 3.1 to 57.4 per 100,000 service members. In gastroenterology clinics, the incidence rate increased from 1.4 to 8.2 per 100,000 person-years, while prevalence increased from 3.3 to 33.4 per 100,000 service members. Discussion: In this study, celiac disease incidence and prevalence increased significantly. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia can lead to maternal and neonatal complications and is a common cause of maternal mortality worldwide. This review has examined the effect of micronutrient supplementation interventions in women identified as having a greater risk of developing pre-eclampsia.Methods: A systematic review was performed using the PRISMA guidelines. The electronic databases MEDLINE, EMBASE and the Cochrane Central Register of Controlled trials were searched for relevant literature and eligible studies identified according to a pre-specified criteria. A meta-analysis of randomised controlled trials (RCTs) was conducted to examine the effect of micronutrient supplementation on pre-eclampsia in high-risk women.Results: Twenty RCTs were identified and supplementation included vitamin C and E (n = 7), calcium (n = 5), vitamin D (n = 3), folic acid (n = 2), magnesium (n = 1) and multiple micronutrients (n = 2). Sample size and recruitment time point varied across studies and a variety of predictive factors were used to identify participants, with a previous history of pre-eclampsia being the most common. No studies utilised a validated prediction model. There was a reduction in pre-eclampsia with calcium (risk difference, -0.15 (-0.27, -0.03, I2 = 83.4%)), and vitamin D (risk difference, -0.09 (-0.17, -0.02, I2 = 0.0%)) supplementation.Conclusion: Our findings show a lower rate of pre-eclampsia with calcium and vitamin D, however, conclusions were limited by small sample sizes, methodological variability and heterogeneity between studies. Further higher quality, large-scale RCTs of calcium and vitamin D are warranted. Exploration of interventions at different time points before and during pregnancy as well as those which utilise prediction modelling methodology, would provide greater insight into the efficacy of micronutrient supplementation intervention in the prevention of pre-eclampsia in high-risk women. [ABSTRACT FROM AUTHOR]

Background: Only a subset of gastric cancer (GC) patients with stage II–III benefits from chemotherapy after surgery. Tumour infiltrating lymphocytes per area (TIL density) has been suggested as a potential predictive biomarker of chemotherapy benefit. Methods: We quantified TIL density in digital images of haematoxylin-eosin (HE) stained tissue using deep learning in 307 GC patients of the Yonsei Cancer Center (YCC) (193 surgery+adjuvant chemotherapy [S + C], 114 surgery alone [S]) and 629 CLASSIC trial GC patients (325 S + C and 304 S). The relationship between TIL density, disease-free survival (DFS) and clinicopathological variables was analysed. Results: YCC S patients and CLASSIC S patients with high TIL density had longer DFS than S patients with low TIL density (P = 0.007 and P = 0.013, respectively). Furthermore, CLASSIC patients with low TIL density had longer DFS if treated with S + C compared to S (P = 0.003). No significant relationship of TIL density with other clinicopathological variables was found. Conclusion: This is the first study to suggest TIL density automatically quantified in routine HE stained tissue sections as a novel, clinically useful biomarker to identify stage II–III GC patients deriving benefit from adjuvant chemotherapy. Validation of our results in a prospective study is warranted. [ABSTRACT FROM AUTHOR]

Neuroimaging protocols play an important role in the timely evaluation and treatment of pediatric stroke and its mimics. MRI protocols for stroke in the pediatric population should be guided by the clinical scenario and neurologic examination, with consideration of age, suspected infarct type and underlying risk factors. Acute stroke diagnosis and causes in pediatric age groups can differ significantly from those in adult populations, and delay in stroke diagnosis among children is a common problem. An awareness of pediatric stroke presentations and risk factors among pediatric emergency physicians, neurologists, pediatricians, subspecialists and radiologists is critical to ensuring timely diagnosis. Given special considerations related to unique pediatric stroke risk factors and the need for sedation in some children, expert consensus guidelines for the imaging of suspected pediatric infarct have been proposed. In this article the authors review standard and rapid MRI protocols for the diagnosis of pediatric stroke, as well as the key differences between pediatric and adult stroke imaging. [ABSTRACT FROM AUTHOR]

Investments in digital health technologies such as artificial intelligence, wearable devices, and telemedicine may support Africa achieve United Nations (UN) Sustainable Development Goal for Health by 2030. We aimed to characterize and map digital health ecosystems of all 54 countries in Africa in the context of endemic infectious and non-communicable diseases (ID and NCD). We performed a cross-national ecological analysis of digital health ecosystems using 20-year data from the World Bank, UN Economic Commission for Africa, World Health Organization, and Joint UN Programme on HIV/AIDS. Spearman's rank correlation coefficients were used to characterize ecological correlations between exposure (technology characteristics) and outcome (IDs and NCDs incidence/mortality) variables. Weighted linear combination model was used as the decision rule, combining disease burden, technology access, and economy, to explain, rank, and map digital health ecosystems of a given country. The perspective of our analysis was to support government decision-making. The 20-year trend showed that technology characteristics have been steadily growing in Africa, including internet access, mobile cellular and fixed broadband subscriptions, high-technology manufacturing, GDP per capita, and adult literacy, while many countries have been overwhelmed by a double burden of IDs and NCDs. Inverse correlations exist between technology characteristics and ID burdens, such as fixed broadband subscription and incidence of tuberculosis and malaria, or GDP per capita and incidence of tuberculosis and malaria. Based on our models, countries that should prioritize digital health investments were South Africa, Nigeria, and Tanzania for HIV; Nigeria, South Africa, and Democratic Republic of the Congo (DROC) for tuberculosis; DROC, Nigeria, and Uganda for malaria; and Egypt, Nigeria, and Ethiopia for endemic NCDs including diabetes, cardiovascular disease, respiratory diseases, and malignancies. Countries such as Kenya, Ethiopia, Zambia, Zimbabwe, Angola, and Mozambique were also highly affected by endemic IDs. By mapping digital health ecosystems in Africa, this study provides strategic guidance about where governments should prioritize digital health technology investments that require preliminary analysis of country-specific contexts to bring about sustainable health and economic returns. Building digital infrastructure should be a key part of economic development programs in countries with high disease burdens to ensure more equitable health outcomes. Though infrastructure developments alongside digital health technologies are the responsibility of governments, global health initiatives can cultivate digital health interventions substantially by bridging knowledge and investment gaps, both through technology transfer for local production and negotiation of prices for large-scale deployment of the most impactful digital health technologies. [ABSTRACT FROM AUTHOR]

Resistance to standard and novel therapies remains the main obstacle to cure in acute myeloid leukaemia (AML) and is often driven by metabolic adaptations which are therapeutically actionable. Here we identify inhibition of mannose-6-phosphate isomerase (MPI), the first enzyme in the mannose metabolism pathway, as a sensitizer to both cytarabine and FLT3 inhibitors across multiple AML models. Mechanistically, we identify a connection between mannose metabolism and fatty acid metabolism, that is mediated via preferential activation of the ATF6 arm of the unfolded protein response (UPR). This in turn leads to cellular accumulation of polyunsaturated fatty acids, lipid peroxidation and ferroptotic cell death in AML cells. Our findings provide further support to the role of rewired metabolism in AML therapy resistance, unveil a connection between two apparently independent metabolic pathways and support further efforts to achieve eradication of therapy-resistant AML cells by sensitizing them to ferroptotic cell death.Metabolic rewiring is involved in acute myeloid leukaemia (AML) maintenance. Here the authors show that the inhibition of mannose-6-phosphate isomerase in the mannose metabolism pathway sensitizes AML to FLT3-tyrosine kinase inhibitor and standard chemotherapy via enhancing lipid peroxidation and ferroptotic cell death. [ABSTRACT FROM AUTHOR]

The current subjective histopathological assessment of cutaneous melanoma is challenging. The application of image analysis algorithms to histological images may facilitate improvements in workflow and prognostication. To date, several individual algorithms applied to melanoma histological images have been reported with variations in approach and reported accuracies. Histological digital images can be created using a camera mounted on a light microscope, or through whole slide image (WSI) generation using a whole slide scanner. Before any such tool could be integrated into clinical workflow, the accuracy of the technology should be carefully evaluated and summarised. Therefore, the objective of this review was to evaluate the accuracy of existing image analysis algorithms applied to digital histological images of cutaneous melanoma. Database searching of PubMed and Embase from inception to 11th March 2022 was conducted alongside citation checking and examining reports from organisations. All studies reporting accuracy of any image analysis applied to histological images of cutaneous melanoma, were included. The reference standard was any histological assessment of haematoxylin and eosin-stained slides and/or immunohistochemical staining. Citations were independently deduplicated and screened by two review authors and disagreements were resolved through discussion. The data was extracted concerning study demographics; type of image analysis; type of reference standard; conditions included and test statistics to construct 2 × 2 tables. Data was extracted in accordance with our protocol and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Diagnostic Test Accuracy (PRISMA-DTA) Statement. A bivariate random-effects meta-analysis was used to estimate summary sensitivities and specificities with 95% confidence intervals (CI). Assessment of methodological quality was conducted using a tailored version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The primary outcome was the pooled sensitivity and specificity of image analysis applied to cutaneous melanoma histological images. Sixteen studies were included in the systematic review, representing 4,888 specimens. Six studies were included in the meta-analysis. The mean sensitivity and specificity of automated image analysis algorithms applied to melanoma histological images was 90% (CI 82%, 95%) and 92% (CI 79%, 97%), respectively. Based on limited and heterogeneous data, image analysis appears to offer high accuracy when applied to histological images of cutaneous melanoma. However, given the early exploratory nature of these studies, further development work is necessary to improve their performance. [ABSTRACT FROM AUTHOR]

Women of reproductive age are a group of particular concern with regards to vaccine uptake, related to their unique considerations of menstruation, fertility, and pregnancy. To obtain vaccine uptake data specific to this group, we obtained vaccine surveillance data from the Office for National Statistics, linked with COVID-19 vaccination status from the National Immunisation Management Service, England, from 8 Dec 2020 to 15 Feb 2021; data from 13,128,525 such women at population-level, were clustered by age (18–29, 30–39, and 40–49 years), self-defined ethnicity (19 UK government categories), and index of multiple deprivation (IMD, geographically-defined IMD quintiles). Here we show that among women of reproductive age, older age, White ethnicity and being in the least-deprived index of multiple deprivation are each independently associated with higher vaccine uptake, for first and second doses; however, ethnicity exerts the strongest influence (and IMD the weakest). These findings should inform future vaccination public messaging and policy.Women of reproductive age may have specific concerns relating to perceived impacts on fertility and menstrual cycles that make them hesitant to receive COVID-19 vaccination. In this study, the authors explore COVID-19 vaccine uptake rates in women of reproductive age using linked data for ~13 million women in England. [ABSTRACT FROM AUTHOR]

Purpose: The immunomodulatory properties of n-3 long chain polyunsaturated fatty acids (LCPUFA) are reported to reduce bone loss through alteration of bone remodelling and n-3 LCPUFA, therefore, may benefit bone health in post-menopausal women, a vulnerable group at high risk of osteoporosis. Methods: Measures of bone mineral density (BMD) were determined using dual energy X-ray absorptiometry (DEXA) in 300 post-menopausal women. The bone turnover markers osteocalcin (OC), C-terminal telopeptides of type 1 collagen (CTX) and total alkaline phosphatase were quantified in serum along with urinary creatinine corrected deoxypyridinoline (DPD/Cr) and CTX/Cr and the CTX:OC ratio calculated. Total serum n-6 PUFA (LA + AA) and n − 3 LCPUFA (ALA + EPA + DPA + DHA) were measured and the n − 6:n − 3 ratio was calculated. Results: Mean (SD) age and body mass index (BMI) were 61 (6.4) years and 27.4 (4.8) kg/m2, respectively with participants being 12.6 (7.6) years post-menopause. Multiple regression analysis identified no association between n-3 LCPUFA and any of the measures of T-score or BMD albeit a significant positive association between total n − 3 LCPUFA and femur BMD (β = 0.287; p = 0.043) was observed within those women with a low n − 6:n − 3 ratio. There was a significant inverse association between ALA and urinary DPD/Cr (β = − 0.141; p = 0.016). Conclusion: A favourable low n − 6:n − 3 ratio was associated with higher femur BMD and a higher n − 3 LCPUFA (ALA) was associated with lower bone resorption. These results support a beneficial role for n − 3 LCPUFA in reducing postmenopausal bone resorption and favourably influencing BMD. Trial number & date of registration: ISRCTN63118444, 2nd October 2009, "Retrospectively registered". [ABSTRACT FROM AUTHOR]

Most research investigating inequality as a moderator of the effect of income on wellbeing focuses on inequality within geographic contexts. This study asks whether the association of income with subjective wellbeing varies with level of inequality within groups defined by the intersection of dichotomized race (white versus non-white) and gender. Two dimensions of subjective wellbeing are investigated—life (dis)satisfaction, and disappointment in one's life achievements. Results of partial proportional odds and logistic regression analyses of data from the study of Midlife Development in the United States (MIDUS) indicate that the association of individual earnings with life (dis)satisfaction varies by level of inequality within intersectional groups. No evidence for moderation is observed in the analysis of disappointment. Within-group inequality varies much more by gender than race, and the results can be interpreted as indicating a gender difference in the effect of income on life satisfaction. The results are also consistent with the income rank hypothesis, which proposes that income effects will be larger among those in lower inequality groups than those in higher inequality groups. Although the statistical power to evaluate race differences is limited by the size and composition of the MIDUS sample, additional analyses suggest that the income-rank pattern might extend to race differences in (dis)satisfaction. The results can be broadly interpreted as suggesting that intersectional inequality does not influence the aspirations that provide the comparative standard for disappointment, but it does shape the way that the contemporaneous earnings differences relevant to life (dis)satisfaction are framed in social comparisons. [ABSTRACT FROM AUTHOR]

Purpose: Abdominal wall hernias are common in the UK and many present in an emergent fashion. The widespread introduction of computed tomography (CT) imaging has transformed surgical practice but out of hours access can be limited by hospital resources and introduce delays. We investigated the influence of preoperative CT imaging in acutely symptomatic hernia and the association with surgical delay and risks of bowel ischemia. Methods: A retrospective analysis of patients undergoing emergency hernia surgery between 2013 and 2021 in a busy UK district general hospital. We evaluated the role of preoperative CT and its influence on timing of surgery, postoperative complications, critical care admission and hospital length of stay. Results: Five hundred and five patients were studied. Of these, 191 had a preoperative CT scan. Sites of hernia included inguinal in 164 patients (33%); umbilical in 164 (33%); femoral in 69 (14%); incisional in 69 (14%); epigastric in 30 (6%) and Spigelian hernia 9 (2%). Preoperative CT imaging was associated with surgical delay (22.0 h vs 13.0 h, p < 0.001) and an increased need for bowel resection (12% vs 6%, p = 0.027). Delay in surgery was not associated with increased postoperative complications (5% vs 4%, p = 0.474) but was associated with increased critical care admission (11.0% vs 4.8%, p = 0.014). Conclusions: Preoperative CT scan for emergent hernias can delay often inevitable surgery and is associated with an increasing need for more complex, resectional surgery. [ABSTRACT FROM AUTHOR]

Recurrent infections and low IgG treated with immunoglobulin replacement therapy have been reported in one patient [[3]]. Early recognition, evaluation, and appropriate treatment for immune abnormalities in patients with MOPD I/III may improve survival and quality of life for these patients. Based on the report of these 2 patients, as well as the I RNU4ATAC i spectrum disorder for which it is a part, immune deficiency is a likely feature of MOPD I/III, similar to other I RNU4ATAC i -opathies. Immunoglobulin replacement therapy may have decreased frequency and severity of infections and extended life expectancy for these patients. [Extracted from the article]

Purpose: Estrogen receptor 1 (ESR1) mutations and fusions typically arise in patients with hormone receptor-positive breast cancer after aromatase inhibitor therapy, whereby ESR1 is constitutively activated in a ligand-independent manner. These variants can impact treatment response. Herein, we characterize ESR1 variants among molecularly profiled advanced breast cancers. Methods: DNA next-generation sequencing (592-gene panel) data from 9860 breast cancer samples were retrospectively reviewed. Gene fusions were detected using the ArcherDx fusion assay or whole transcriptome sequencing (n = 344 and n = 4305, respectively). Statistical analyses included Chi-square and Fisher's exact tests. Results: An ESR1 ligand-binding domain (LBD) mutation was detected in 8.6% of tumors evaluated and a pathogenic ESR1 fusion was detected in 1.6%. Most ESR1 LBD mutations/fusions were from estrogen receptor (ER)-positive samples (20.1% and 4.9%, respectively). The most common ESR1 LBD mutations included D538G (3.3%), Y537S (2.3%), and E380Q (1.1%) mutations. Among biopsy sites, ESR1 LBD mutations were most observed in liver metastases. Pathogenic ESR1 fusions were identified in 76 samples (1.6%) with 40 unique fusion partners. Evaluating co-alterations, ESR1 variant (mutation/fusion) samples more frequently expressed androgen receptor (78.0% vs 58.6, P < 0.0001) and less frequently immune checkpoint proteins than ESR1 wild-type (PD-1 20.0% vs 53.4, P < 0.05; immune cell PD-L1 10.0% vs 30.2, P < 0.0001). Conclusion: We have described one of the largest series of ESR1 fusions reported. ESR1 LBD mutations were commonly identified in ER-positive disease. Limited data exists regarding the clinical impact of ESR1 fusions, which could be an area for future therapeutic exploration. [ABSTRACT FROM AUTHOR]

Learning-related changes in brain activity are thought to underlie adaptive behaviours1,2. For instance, the learning of a reward site by rodents requires the development of an over-representation of that location in the hippocampus3–6. How this learning-related change occurs remains unknown. Here we recorded hippocampal CA1 population activity as mice learned a reward location on a linear treadmill. Physiological and pharmacological evidence suggests that the adaptive over-representation required behavioural timescale synaptic plasticity (BTSP)7. BTSP is known to be driven by dendritic voltage signals that we proposed were initiated by input from entorhinal cortex layer 3 (EC3). Accordingly, the CA1 over-representation was largely removed by optogenetic inhibition of EC3 activity. Recordings from EC3 neurons revealed an activity pattern that could provide an instructive signal directing BTSP to generate the over-representation. Consistent with this function, our observations show that exposure to a second environment possessing a prominent reward-predictive cue resulted in both EC3 activity and CA1 place field density that were more elevated at the cue than at the reward. These data indicate that learning-related changes in the hippocampus are produced by synaptic plasticity directed by an instructive signal from the EC3 that seems to be specifically adapted to the behaviourally relevant features of the environment.Analysis of the activity of CA1 cells in mice performing a learning task shows that the entorhinal cortex signals behavioural timescale synaptic plasticity to generate learning-related changes in the hippocampus. [ABSTRACT FROM AUTHOR]

Public access automated external defibrillators (AEDs) represent emergency medical devices that may be used by untrained lay-persons in a life-critical event. As such their usability must be confirmed through simulation testing. In 2020 the novel coronavirus caused a global pandemic. In order to reduce the spread of the virus, many restrictions such as social distancing and travel bans were enforced. Usability testing of AEDs is typically conducted in-person, but due to these restrictions, other usability solutions must be investigated. Two studies were conducted, each with 18 participants: (1) an in-person usability study of an AED conducted in an office space, and (2) a synchronous remote usability study of the same AED conducted using video conferencing software. Key metrics associated with AED use, such as time to turn on, time to place pads and time to deliver a shock, were assessed in both studies. There was no difference in time taken to turn the AED on in the in-person study compared to the remote study, but the time to place electrode pads and to deliver a shock were significantly lower in the in-person study than in the remote study. Overall, the results of this study indicate that remote user testing of public access defibrillators may be appropriate in formative usability studies for determining understanding of the user interface. [ABSTRACT FROM AUTHOR]

This case study describes the failure of a M7x1 high-speed steel tap that experienced a torsional brittle fracture, while a crescent wrench was applied by hand to create threads in a steel brake caliper of a motorcycle. During this process, the tap was fractured into two pieces forming a 45° angle with respect to the long axis of the tap. The crack origin was in one of the flutes of the tap. The hardness of the original tap was well below the recommended per ASTM A600. The root cause of the failure and crack origin was determined through scanning electron microscopy (SEM), and a finite element analysis (FEA) was used to analyze the performance of the part under normal loading conditions. [ABSTRACT FROM AUTHOR]

Let Γ g be the fundamental group of a closed connected orientable surface of genus g ≥ 2 . We introduce a combinatorial structure of core surfaces, that represent subgroups of Γ g . These structures are (usually) 2-dimensional complexes, made up of vertices, labeled oriented edges, and 4g-gons. They are compact whenever the corresponding subgroup is finitely generated. The theory of core surfaces that we initiate here is analogous to the influential and fruitful theory of Stallings core graphs for subgroups of free groups. [ABSTRACT FROM AUTHOR]