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The management of patients with Apert syndrome (AS) is complex and reflects the multisystem disease as a result of premature fusion of cranial vault, cranial base and midface sutures as well as extremity anomalies characterised by syndactyly. Early cranial sutural fusion results in craniocerebral disproportion which can lead to crisis surgical intervention due to raised intracranial pressure, ophthalmic and compromised airway concerns. Childhood inventions are often determined by psychosocial concerns and adult surgical interventions are often determined by cosmetic concerns. Treatments are provided by many different specialists within multidisciplinary teams (MDT). The treatment pathway extends from birth well into adulthood and is often associated with a heavy burden of care. Due to the extensive nature of the interaction with these patients MDT members have opportunities to provide enhanced patient-centred care and support.This case report provides an overview of the current knowledge of the aetiology of AS, illustrates the pathway of surgical and non-surgical management of AS and provides a long-term review of the dentofacial treatment outcomes.By having a better understanding of the impact of AS and treatment provided, MDT members can not only provide improved clinical treatment but also offer improved patient experiences for those with craniofacial anomalies, in particular, an increased awareness of the psychosocial challenges they endure.

We report on the 1,000-element transition-edge sensor (TES) x-ray spectrometer implementation of the TOMographic Circuit Analysis Tool (TOMCAT). TOMCAT combines a high spatial resolution scanning electron microscope (SEM) with a highly efficient and pixelated TES spectrometer to reconstruct three-dimensional maps of nanoscale integrated circuits (ICs). A 240-pixel prototype spectrometer was recently used to reconstruct ICs at the 130 nm technology node, but to increase imaging speed to more practical levels, the detector efficiency needs to be improved. For this reason, we are building a spectrometer that will eventually contain 3,000 TES microcalorimeters read out with microwave superconducting quantum interference device (SQUID) multiplexing, and we currently have commissioned a 1,000 TES subarray. This still represents a significant improvement from the 240-pixel system and allows us to begin characterizing the full spectrometer performance. Of the 992 maximimum available readout channels, we have yielded 818 devices, representing the largest number of TES x-ray microcalorimeters simultaneously read out to date. These microcalorimeters have been optimized for pulse speed rather than purely energy resolution, and we measure a FWHM energy resolution of 14 eV at the 8.0 keV Cu K$\alpha$ line., Comment: 5 pages, 4 figures, submitted to IEEE Transactions on Applied Superconductivity

BACKGROUND: Traumatic life events are associated with the development of psychiatric and chronic medical illnesses. This exploratory study examined the relationship between traumatic life events and the gut microbiota among adult psychiatric inpatients. METHODS: 105 adult psychiatric inpatients provided clinical data and a single fecal sample shortly after admission. A modified version of the Stressful Life Events Screening Questionnaire was used to quantify history of traumatic life events. 16S rRNA gene sequencing was used to analyze the gut microbial community. RESULTS: Gut microbiota diversity was not associated with overall trauma score or any of the three trauma factor scores. Upon item-level analysis, history of childhood physical abuse was uniquely associated with beta diversity. Linear Discriminant Analysis Effect Size (LefSe) analyses revealed that childhood physical abuse was associated with abundance of distinct bacterial taxa associated with inflammation. LIMITATIONS: This study did not account for dietary differences, though diet was highly restricted as all participants were psychiatric inpatients. Absolute variance accounted for by the taxa was small though practically meaningful. The study was not powered for full subgroup analysis based on race and ethnicity. CONCLUSIONS: This study is among the first to demonstrate a relationship between childhood physical abuse and gut microbiota composition among adult psychiatric patients. These findings suggest that early childhood adverse events may have long-conferred systemic consequences. Future efforts may target the gut microbiota for the prevention and/or treatment of psychiatric and medical risk associated with traumatic life events.

This multi-authored book review explores the current state of the field of Autism Theology through a discussion of four recent publications. A concluding section reflects on several key themes in the individual reviews, drawing particular attention to: Autism Theology's focus on the ideas and practices which enable autistic people’s thriving; the importance of the inclusion of different voices in the conversation (including those who are non- or minimally speaking); and the richness which autistic people’s presence and contributions bring to theology and to the Church as a whole. Reviewed works:Claire Williams, Peculiar Discipleship: An Autistic Liberation Theology (London: SCM Press, 2023), pp. 272, ISBN 978-0334063063.Ruth M. Dunster, The Autism of Gxd: An Atheological Love Story (Eugene, OR: Pickwick Publications, 2022), pp. xix + 420, ISBN 978-1725268357.Stewart Rapley, Autistic Thinking in the Life of the Church (London: SCM Press, 2021), pp. xiv + 178, ISBN 978-0334060871.Cynthia Tam, Kinship in the Household of God: Towards a Practical Theology of Belonging and Spiritual Care of People with Profound Autism (Eugene, OR: Pickwick Publications, 2021), pp. x + 191, ISBN 978-1725274419.

PURPOSE Given the heterogeneity and improvement in outcomes for metastatic breast cancer (MBC), we developed a staging system that refines prognostic estimates for patients with metastatic cancer at the time of initial diagnosis, de novo MBC (dnMBC), on the basis of survival outcomes and disease-related variables. METHODS Patients with dnMBC (2010-2016) were selected from the National Cancer Database (NCDB). Recursive partitioning analysis (RPA) was used to group patients with similar overall survival (OS) on the basis of clinical T category, grade, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2, histology, organ system site of metastases (bone-only, brain-only, visceral), and number of organ systems involved. Three-year OS rates were used to assign a final stage: IVA: >70%, IVB: 50%-70%, IVC: 25 to RESULTS At a median follow-up of 52.9 months, the median OS of the original cohort (N = 42,467) was 35.4 months (95% CI, 34.8 to 35.9). RPA stratified patients into 53 groups with 3-year OS rates ranging from 73.5% to 5.7%; these groups were amalgamated into four stage groups: 3-year OS, A = 73.2%, B = 61.9%, C = 40.1%, and D = 17% (log-rank P < .001). After bootstrapping, the survival outcomes for the four stages remained significantly different (log-rank P < .001). This staging system was then validated using SEER data (N = 20,469) and a separate cohort from the NCDB (N = 7,645) (both log-rank P < .001). CONCLUSION Our findings regarding the heterogeneity in outcomes for patients with dnMBC could guide future revisions of the current American Joint Committee on Cancer staging guidelines for patients with newly diagnosed stage IV disease. Our findings should be independently confirmed.

Background Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, the understanding of resistance mechanisms is poor, which is hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine resistance determinants, we combined experimental evolution, protein modelling, genome sequencing, and phenotypic data. Methods For this in-vitro and in-silico data analysis, we used a novel in-vitro evolutionary model using subinhibitory drug concentrations to select bedaquiline-resistant and clofazimine-resistant mutants. We determined bedaquiline and clofazimine minimum inhibitory concentrations and did Illumina and PacBio sequencing to characterise selected mutants and establish a mutation catalogue. This catalogue also includes phenotypic and genotypic data of a global collection of more than 14 000 clinical Mycobacterium tuberculosis complex isolates, and publicly available data. We investigated variants implicated in bedaquiline resistance by protein modelling and dynamic simulations. Findings We discerned 265 genomic variants implicated in bedaquiline resistance, with 250 (94%) variants affecting the transcriptional repressor (Rv0678) of the MmpS5–MmpL5 efflux system. We identified 40 new variants in vitro, and a new bedaquiline resistance mechanism caused by a large-scale genomic rearrangement. Additionally, we identified in vitro 15 (7%) of 208 mutations found in clinical bedaquiline-resistant isolates. From our in-vitro work, we detected 14 (16%) of 88 mutations so far identified as being associated with clofazimine resistance and also seen in clinically resistant strains, and catalogued 35 new mutations. Structural modelling of Rv0678 showed four major mechanisms of bedaquiline resistance: impaired DNA binding, reduction in protein stability, disruption of protein dimerisation, and alteration in affinity for its fatty acid ligand. Interpretation Our findings advance the understanding of drug resistance mechanisms in M tuberculosis complex strains. We have established an extended mutation catalogue, comprising variants implicated in resistance and susceptibility to bedaquiline and clofazimine. Our data emphasise that genotypic testing can delineate clinical isolates with borderline phenotypes, which is essential for the design of effective treatments. Funding Leibniz ScienceCampus Evolutionary Medicine of the Lung, Deutsche Forschungsgemeinschaft, Research Training Group 2501 TransEvo, Rhodes Trust, Stanford University Medical Scientist Training Program, National Institute for Health and Care Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Bill & Melinda Gates Foundation, Wellcome Trust, and Marie Skłodowska-Curie Actions.

Artificial intelligence, machine learning, and algorithmic techniques in general, provide two crucial abilities with the potential to improve decision-making in the context of allocation of scarce societal resources. They have the ability to flexibly and accurately model treatment response at the individual level, potentially allowing us to better match available resources to individuals. In addition, they have the ability to reason simultaneously about the effects of matching sets of scarce resources to populations of individuals. In this work, we leverage these abilities to study algorithmic allocation of scarce societal resources in the context of homelessness. In communities throughout the United States, there is constant demand for an array of homeless services intended to address different levels of need. Allocations of housing services must match households to appropriate services that continuously fluctuate in availability, while inefficiencies in allocation could “waste” scarce resources as households will remain in-need and re-enter the homeless system, increasing the overall demand for homeless services. This complex allocation problem introduces novel technical and ethical challenges. Using administrative data from a regional homeless system, we formulate the problem of “optimal” allocation of resources given data on households with need for homeless services. The optimization problem aims to allocate available resources such that predicted probabilities of household re-entry are minimized. The key element of this work is its use of a counterfactual prediction approach that predicts household probabilities of re-entry into homeless services if assigned to each service. Through these counterfactual predictions, we find that this approach has the potential to improve the efficiency of the homeless system by reducing re-entry, and, therefore, system-wide demand. However, efficiency comes with trade-offs - a significant fraction of households are assigned to services that increase probability of re-entry. To address this issue as well as the inherent fairness considerations present in any context where there are insufficient resources to meet demand, we discuss the efficiency, equity, and fairness issues that arise in our work and consider potential implications for homeless policies.

Objectives: The Nottingham hip fracture score (NHFS) and the Surgical outcome risk tool (SORT) are both validated scoring systems used to predict mortality rates in patient with Fractured neck of femur (FnF). The primary aim of this study was to compare the accuracy of the predicted 30-day mortality rates between NHFS and SORT in patients with FnF. The secondary aim was to investigate the influence of patient and surgical factors on 30-day mortality. Methods: The NHFS and SORT score was collected from 212 patients admitted with FnF. Variables including hip fracture type, surgical procedure and peri-operative haemoglobin, gender and ASA grade were also collected and further analysed to assess their influence on 30-day mortality rates. Results: Overall actual 30-day mortality rate for the study population was 11.3% (n=24). There was a significant difference between the mean predicted 30-day mortality for the NHFS (8.0%) and the SORT score (7.0%, p=0.006). The was no difference in mortality rates between the different fracture types (p=0.889). There was a significant difference in mortality rates when comparing surgical procedures (p=0.031). Patients who had a notable fall in haemoglobin peri-operatively had significantly higher mortality rates (p

Distal radius fractures (DRFs) are frequently complicated by acute carpal tunnel syndrome (CTS), which, if unrecognized, can cause permanent median neuropathy. Some surgeons recommend “prophylactic” carpal tunnel release (CTR) during open reduction and internal fixation (ORIF) of DRF. Patient-reported outcomes (PROs) and safety data regarding prophylactic vs symptomatic CTR strategies during DRF fixation are lacking. We conducted a retrospective review of two management strategies for DRFs at our institution (2017 to 2019). Group 1 consisted of patients operated on by two surgeons performing ORIF and symptomatic CTR only for acute CTS. Group 2 consisted of patients operated on by a third surgeon performing ORIF and prophylactic CTR on all patients irrespective of median nerve symptoms. The PROs included QuickDASH Wrist and PROMIS physical/mental health preoperatively vs at final follow-up. Demographic information, complications, and return to the operating room were recorded. Group 1 (36 patients) and group 2 (76 patients) were demographically similar. The mechanism of injury was more severe in group 1 ( P P P >.05). A prophylactic CTR strategy is not associated with improved PROs compared with a symptomatic strategy during ORIF of DRF. [ Orthopedics . 202x;4x(x);xx–xx.]

Summary: Ventilator‐associated pneumonia commonly occurs in critically ill patients. Clinical suspicion results in overuse of antibiotics, which in turn promotes antimicrobial resistance. Detection of volatile organic compounds in the exhaled breath of critically ill patients might allow earlier detection of pneumonia and avoid unnecessary antibiotic prescription. We report a proof of concept study for non‐invasive diagnosis of ventilator‐associated pneumonia in intensive care (the BRAVo study). Mechanically ventilated critically ill patients commenced on antibiotics for clinical suspicion of ventilator‐associated pneumonia were recruited within the first 24 h of treatment. Paired exhaled breath and respiratory tract samples were collected. Exhaled breath was captured on sorbent tubes and then analysed using thermal desorption gas chromatography–mass spectrometry to detect volatile organic compounds. Microbiological culture of a pathogenic bacteria in respiratory tract samples provided confirmation of ventilator‐associated pneumonia. Univariable and multivariable analyses of volatile organic compounds were performed to identify potential biomarkers for a ‘rule‐out’ test. Ninety‐six participants were enrolled in the trial, with exhaled breath available from 92. Of all compounds tested, the four highest performing candidate biomarkers were benzene, cyclohexanone, pentanol and undecanal with area under the receiver operating characteristic curve ranging from 0.67 to 0.77 and negative predictive values from 85% to 88%. Identified volatile organic compounds in the exhaled breath of mechanically ventilated critically ill patients show promise as a useful non‐invasive ‘rule‐out’ test for ventilator‐associated pneumonia.

The peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) family of transcriptional coactivators are regulators of mitochondrial oxidative capacity and content in skeletal muscle. Many of these conclusions are based primarily on gain-of-function studies using muscle-specific overexpression of PGC1s. We have previously reported that genetic deletion of both PGC-1α and PGC-1β in adult skeletal muscle resulted in a significant reduction in oxidative capacity with no effect on mitochondrial content. However, the contribution of PGC-1-related coactivator (PRC), the third PGC-1 family member, in regulating skeletal muscle mitochondria is unknown. Therefore, we generated an inducible skeletal muscle-specific PRC knockout mouse (iMS-PRC-KO) to assess the contribution of PRC in skeletal muscle mitochondrial function. We measured mRNA expression of electron transport chain (ETC) subunits as well as markers of mitochondrial content in the iMS-PRC-KO animals and observed an increase in ETC gene expression and mitochondrial content. Furthermore, the increase in ETC gene expression and mitochondrial content was associated with increased expression of PGC-1α and PGC-1β. We therefore generated an adult-inducible PGC-1 knockout mouse in which all PGC-1 family members are deleted (iMS-PGC-1TKO). The iMS-PGC-1TKO animals exhibited a reduction in ETC mRNA expression and mitochondrial content. These data suggest that in the absence of PRC alone, compensation occurs by increasing PGC-1α and PGC-1β to maintain mitochondrial content. Moreover, the removal of all three PGC-1s in skeletal muscle results in a reduction in both ETC mRNA expression and mitochondrial content. Taken together, these results suggest that PRC plays a role in maintaining baseline mitochondrial content in skeletal muscle.

Black transness has been marked and made broken by necropolitical systems of power. Theories and politics of and for black trans women have often prioritized a rejection of or confrontation with this “state of brokenness,” as poet Nat Raha terms it. Visual artist Tourmaline offers a different relationship with brokenness in her call to “come undone,” whereby those who are “broken” can gather their broken pieces together not to heal but to give and share one's pieces with another. This essay engages Tourmaline's Salacia (2019), a film about the life of Mary Jones, a black trans sex worker who became infamous in 1836 following her arrest in New York City, as producing a black trans aesthetic of brokenness. Using a collage style of placing distinct frames upon frames, Tourmaline mixes speculative retellings of Jones's life alongside archival footage of Latina trans activist Sylvia Rivera to create an image built from the pieces and fragments of the trans archive. This aesthetic of brokenness offers an aestheticization of Saidiya Hartman's “critical fabulation” that holds and cares for black transness, a practice of gathering and being-with and being-for.

Background and Aims: Some eosinophilic esophagitis (EoE) patients can have a decline in eosinophil count after proton pump inhibitor (PPI) treatment without achieving histologic response, but little is known about this group. We aimed to determine the effect of PPIs on reducing esophageal eosinophilia in patients deemed non-responsive to PPI therapy. Methods: We analyzed prospectively collected cohort data from newly diagnosed adults with EoE who were histologic non-responders (≥15 eos/hpf) to PPI-only therapy. Symptoms, endoscopic histologic features were assessed before and after PPI. Pre- and post-PPI treatment esophageal biopsies were read by pathologists to determine peak eosinophil counts and other histologic findings. Results: Of 125 patients, peak eosinophil counts were 102.1 ± 69.8 and 102.9 ± 101.1 (p=0.93) before and after PPI treatment, respectively, but lamina propria fibrosis decreased from 97% to 41% (p

This paper demonstrates the potential for crowdsourced rainfall data to infill gaps in the official rain gauge network and to provide new datasets for use in research. We use data from the Met Office Weather Observation Website (WOW) over 10 years (2011–2020) to generate two open-source datasets for Britain; multi-parameter raw data in an easy-to-use format; and an hourly rainfall dataset. We have compiled and prepared the data and detail here station selection, rain depth calculation, and data resampling to hourly intervals to create a consistent dataset for further processing (including statistical quality control) and application. Mapping the new rainfall dataset establishes that WOW observations fill spatial gaps in the official ground-based rain gauge network over Britain, particularly in urban areas. This could be particularly useful for post-event analysis of rainfall that results in pluvial flash flooding. Here, we focus on Britain but due to agreements with meteorological services in Belgium, the Netherlands, Australia, New Zealand, Sweden, and the Republic of Ireland, plus many citizen scientists globally opting to share data via WOW, there is potential for the development of similar datasets using these methods around the world.

School attendance zone boundary (AZB) data remain relatively underdocumented and understudied within the field of education, despite their critical implications for educational (in)equity. AZBs shape student outcomes and residential sorting patterns both by determining the public schools a student is assigned to and by signaling neighborhood characteristics to prospective homebuyers. The limited access, regulation, and review of AZB data to date has left a gap in the knowledge base, having the potential to leave intact (and exacerbate) patterns of segregation that maintain inequities in educational opportunity. Lack of data also limits our ability to know whether and when AZBs may mitigate segregation. In this brief, we examine a novel data collection effort of current and historical AZB data—the Longitudinal School Attendance Boundary System—to explore the contextual and political factors associated with data access and data quality. We aim to show how factors that hinder access to quality AZB data affect the study of educational equity, and we advocate for more comprehensive, top-down governmental efforts to create, maintain, and collect these data.

Introduction. Inguinal hernia repair (IHR) is a common procedure performed by general surgeons in rural community hospitals. Infection and recurrence rates for three types of IHR over two years at a rural Kansas hospital were analyzed. Previous research has shown outcomes regarding pain at six weeks were typically no different, and neither were long-term results, between open and laparoscopic techniques. However, there were fewer data showing the outcomes of these three hernia repair approaches in rural settings. Methods. This was a retrospective, cross-sectional study using data collected from the electronic medical record (EMR) of a small hospital in central Kansas. Data from adult patients who had undergone IHRs over a two-year period (2018-2019) were deidentified and described using frequencies and percentages. This study used multi-variate logistic regression to examine the association of patient, surgeon, and surgical procedure characteristics on the occurrence of post-operative complications. Results. Of the patients who received IHR, 46 were male and 5 were female. Mean age was 66 years, with a minimum of 34 and maximum ≥ 89 years. There were 14 total post-operative complications; two were superficial infections. There were no recurrences. Conclusions. The sample size for each procedure type was too small to allow for statistical testing. However, the hospital had no recurrences. Future research should follow-up with this and other rural hospitals and perform a direct comparison of hernia surgery outcomes with those at a larger, more urban hospital, to understand potential differences by hospital size.

Viral load in infant saliva and urine was assessed to predict sensorineural hearing loss (SNHL) in children with congenital cytomegalovirus infection. Viral load was higher in symptomatic infants. Viral load in asymptomatic children with and without SNHL did not differ. Congenital cytomegalovirus infection viral load in urine and saliva does not predict hearing loss.