Orphan high field superconductivity in non-superconducting uranium ditelluride.

Reentrant superconductivity is an uncommon phenomenon in which the destructive effects of magnetic field on superconductivity are mitigated, allowing a zero-resistance state to survive under conditions that would otherwise destroy it. Typically, the reentrant superconducting region derives from a zero-field parent superconducting phase. Here, we show that in UTe2 crystals extreme applied magnetic fields give rise to an unprecedented high-field superconductor that lacks a zero-field antecedent. This high-field orphan superconductivity exists at angles offset between 29o and 42o from the crystallographic b to c axes with applied fields between 37 T and 52 T. The stability of field-induced orphan superconductivity presented in this work defies both empirical precedent and theoretical explanation and demonstrates that high-field superconductivity can exist in an otherwise non-superconducting material.

Genetic Testing Yield and Clinical Characteristics of Hypertrophic Cardiomyopathy in Understudied Ethnic Groups: Insights From a New Zealand National Registry.

BACKGROUND: Aotearoa/New Zealand has a multiethnic population. Patients with hypertrophic cardiomyopathy (HCM) are enrolled in the national Cardiac Inherited Diseases Registry New Zealand. Here, we report the characteristics of Cardiac Inherited Diseases Registry New Zealand HCM probands with and without pathogenic or likely pathogenic (P/LP) genetic variants for HCM, and assess genetic testing yield and variant spectrum by self-identified ethnicity. METHODS: Probands with HCM and enrolled in Cardiac Inherited Diseases Registry New Zealand who have undergone clinical genetic testing over a 17-year period were included. Clinical data, family history, and genetic test results were analyzed. RESULTS: Of 336 probands, 121 (36%) were women, 220 (66%) were European ethnicity, 41 (12%) were Maori, 26 (8%) were Pacific people, and 49 (15%) were other ethnicities. Thirteen probands (4%) presented with sudden death and 19 (6%) with cardiac arrest. A total of 134 (40%) had a P/LP variant identified; most commonly in the MYBPC3 gene (60%) followed by the MYH7 gene (24%). A P/LP variant was identified in 27% of Maori or Pacific probands versus 43% European or other ethnicity probands (P=0.022); 16% of Maori or Pacific probands had a variant of uncertain significance identified, compared with 9% of European or other ethnicity probands (P=0.092). Women more often had a P/LP variant identified than men (48% versus 35%; P=0.032), and variant-positive probands were younger at clinical diagnosis than variant of uncertain significance/variant-negative probands (39±17 versus 50±17 years; P<0.001) and more likely to have experienced cardiac arrest or sudden death events over their lifetime (P=0.002). CONCLUSIONS: Carriage of a P/LP variant in HCM probands is associated with presentation at younger age, and cardiac arrest or sudden death events. Maori or Pacific probands were less likely to have a P/LP variant identified than European or other ethnicity probands.

Resonant Ultrasound Spectroscopy for Irregularly Shaped Samples and Its Application to Uranium Ditelluride.

Resonant ultrasound spectroscopy (RUS) is a powerful technique for measuring the full elastic tensor of a given material in a single experiment. Previously, this technique was practically limited to regularly shaped samples such as rectangular parallelepipeds, spheres, and cylinders [W. M. Visscher et al. J. Acoust. Soc. Am. 90, 2154 (1991)JASMAN0001-496610.1121/1.401643]. We demonstrate a new method for determining the elastic moduli of irregularly shaped samples, extending the applicability of RUS to a much larger set of materials. We apply this new approach to the recently discovered unconventional superconductor UTe_{2} and provide its elastic tensor at both 300 and 4 kelvin.

Biallelic ATP2B1 variants as a likely cause of a novel neurodevelopmental malformation syndrome with primary hypoparathyroidism.

ATP2B1 encodes plasma membrane calcium-transporting-ATPase1 and plays an essential role in maintaining intracellular calcium homeostasis that regulates diverse signaling pathways. Heterozygous de novo missense and truncating ATP2B1 variants are associated with a neurodevelopmental phenotype of variable expressivity. We describe a proband with distinctive craniofacial gestalt, Pierre-Robin sequence, neurodevelopmental and growth deficit, periventricular heterotopia, brachymesophalangy, cutaneous syndactyly, and persistent hypocalcemia from primary hypoparathyroidism. Proband-parent trio exome sequencing identified compound heterozygous ATP2B1 variants: a maternally inherited splice-site (c.3060+2 T > G) and paternally inherited missense c.2938 G > T; p.(Val980Leu). Reverse-transcription-PCR on the proband's fibroblast-derived mRNA showed aberrantly spliced ATP2B1 transcripts targeted for nonsense-mediated decay. All correctly-spliced ATP2B1 mRNA encoding p.(Val980Leu) functionally causes decreased cellular Ca2+ extrusion. Immunoblotting showed reduced fibroblast ATP2B1. We conclude that biallelic ATP2B1 variants are the likely cause of the proband's phenotype, strengthening the association of ATP2B1 as a neurodevelopmental gene and expanding the phenotypic characterization of a biallelic loss-of-function genotype.

A novel 11 base pair deletion in KMT2C resulting in Kleefstra syndrome 2.

BACKGROUND: Haploinsufficiency of the Lysine Methyltransferase 2C (KMT2C) gene results in the autosomal dominant disorder, Kleefstra syndrome 2. It is an extremely rare neurodevelopmental condition, with 14 previous reports describing varied clinical manifestations including dysmorphic features, delayed psychomotor development and delayed growth. METHODS: Here, we describe a female with global developmental delay, attention deficit disorder, dyspraxia, short stature and subtle non-specific dysmorphic features. To identify causative mutations, whole exome sequencing was performed on the proband and her younger brother with discrete clinical presentation. RESULTS: Whole exome sequencing identified a novel de novo heterozygous 11 bp deletion in KMT2C (c.1759_1769del), resulting in a frameshift mutation and early termination of the protein (p.Gln587SerfsTer7). This variant is the second-most N-terminal reported mutation, located 4171 amino acids upstream of the critical enzymatically active SET domain (required for chromatin modification and histone methylation). CONCLUSION: The majority of the other reported mutations are frameshift mutations upstream of the SET domain and are predicted to result in protein truncation. It is thought that truncation of the SET domain, results functionally in an inability to modify chromatin through histone methylation. This report expands the clinical and genetic characterisation of Kleefstra syndrome 2.

Management of acute perianal abscess: is surgeon specialization associated with improved outcomes?

BACKGROUND: Acute surgical units (ASU) are increasingly being adopted and in our system are staffed by colorectal and non-colorectal general surgeons. This study aims to evaluate whether surgeon specialization was associated with improved outcomes in perianal abscess. METHODS: Patients with perianal abscess admitted to the ASU between 2016 and 2020 were identified from a prospective database and their medical records reviewed. Patients with IBD, treatment for fistula-in-ano within the preceding year, or perianal sepsis of non-cryptoglandular origin were excluded. Patients admitted under an ASU colorectal (CR) consultant were compared with those under a non-CR general surgeon in a retrospective cohort study. Primary outcome was perianal abscess recurrence. For those without initial fistula, hazard of recurrent abscess or fistula was analysed. Multivariable Cox PH regression analysis was performed. RESULTS: Four-hundred and eight patients were included (150 CR, 258 non-CR). The CR group more frequently had a fistula identified at index operation (34.0% versus 10.9%, P < 0.0001). However, Cox multivariable analysis found no difference in hazard of recurrent abscess between groups (HR 1.12, 95% CI 0.65-1.95, P = 0.681)). Abscess recurred in 18.7% CR and 15.5% non-CR. Subsequent fistula developed in 14.7% in both groups. For patients without initial fistula, there was no difference between groups in hazard of recurrent abscess or fistula (HR 1.18, 95% CI 0.69-2.01, P = 0.539). CONCLUSION: Surgeon specialization was not associated with improved outcomes for ASU patients with perianal abscess, albeit with potential selection bias. CR surgeons were more proactive identifying fistulas; this raises the possibility that drainage alone may be adequate treatment.

Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies.

Misregulation of histone lysine methylation is associated with several human cancers and with human developmental disorders. DOT1L is an evolutionarily conserved gene encoding a lysine methyltransferase (KMT) that methylates histone 3 lysine-79 (H3K79) and was not previously associated with a Mendelian disease in OMIM. We have identified nine unrelated individuals with seven different de novo heterozygous missense variants in DOT1L through the Undiagnosed Disease Network (UDN), the SickKids Complex Care genomics project, and GeneMatcher. All probands had some degree of global developmental delay/intellectual disability, and most had one or more major congenital anomalies. To assess the pathogenicity of the DOT1L variants, functional studies were performed in Drosophila and human cells. The fruit fly DOT1L ortholog, grappa, is expressed in most cells including neurons in the central nervous system. The identified DOT1L variants behave as gain-of-function alleles in flies and lead to increased H3K79 methylation levels in flies and human cells. Our results show that human DOT1L and fly grappa are required for proper development and that de novo heterozygous variants in DOT1L are associated with a Mendelian disease.

Acute Colonic Pseudo-obstruction Following Spinal Fixation for Trauma.

BACKGROUND: Acute colonic pseudo-obstruction (ACPO) is a potentially highly morbid surgical complication. The incidence of ACPO following spinal trauma is unknown, but is likely higher than after elective spinal fusion. The purpose of this study was to establish the incidence of ACPO in patients with major trauma undergoing spinal fusion for unstable thoracic and lumbar fracture, and secondly, to characterize the nature of ACPO in this group, including treatment and complications. METHODS: A metropolitan hospital prospective trauma database was utilized to identify all patients from November 2015 to December 2021 meeting major trauma criteria and undergoing thoracic or lumbar spinal fusion for fracture. Individual records were then evaluated for occurrence of ACPO. ACPO was defined as radiologic evidence of colonic dilation without mechanical obstruction in symptomatic patients undergoing dedicated abdominal imaging. RESULTS: After exclusions, 456 patients with major trauma undergoing thoracic or lumbar spinal fusion were identified. ACPO occurred in 34-an incidence rate of 7.5%. There was no evidence of difference in terms of the spinal fracture type, level, surgical approach, or number of segments fused. There were no perforations; only 2 patients required colonoscopic decompression and none required surgical resection. CONCLUSIONS: ACPO occurred at a high frequency in this group of patients, although it required relatively simple treatment. High vigilance for ACPO should be maintained in trauma patients requiring thoracic or lumbar fixation, with a view to early intervention. The etiology driving the high rates of ACPO in this cohort is not understood and would benefit from further investigation.

Rare causes of abdominal pain: a primer for the admitting general surgeon.

The broad uptake of the acute surgical unit (ASU) model of surgical care in Australia has resulted in general surgeons becoming increasingly involved in the management of patients with acute abdominal pain (AAP), some of whom will be labelled as having non-specific abdominal pain (NSAP) (Kinnear N, Jolly S, Herath M, et al. The acute surgical unit: An updated systematic review and meta-analysis. review. Int. J. Surg. 2021;94:106109; Lehane CW, Jootun RN, Bennett M, Wong S, Truskett P. Does an acute care surgical model improve the management and outcome of acute cholecystitis? ANZ J. Surg. 2010;80:438-42). NSAP patients lack a clear diagnosis of surgical pathology based on standard clinical, laboratory and imaging work-up, although they may require ASU admission for pain control and assessment. This article provides a review of uncommon conditions, presenting as AAP, that could possibly be mis-labelled as NSAP, with a focus on aspects of the presentation that may aid diagnosis and management including specific demographic features, clinical findings, key investigations and initial treatment priorities for ASU clinicians. Ultimately, most of the conditions discussed will not require surgical intervention, however, they require a diagnosis to be made and initial treatment planning before on-referral to the appropriate specialty. For the on-call general surgeon, some knowledge of these conditions and an index of suspicion are invaluable for the prompt diagnosis and efficient management of these patients.

Evaluation of Low- and Middle-Income Country Authorship in the Global Orthopaedic Literature.

INTRODUCTION: Extensive research collaborations exist between high-income countries and low- and middle-income countries (LMICs), although prior work has raised concerns regarding equitable representation among LMIC authors. The goal of this bibliometric analysis was to characterize LMIC authorship among indexed orthopaedic journals and identify factors contributing to disparities in representation. METHODS: We identified all articles appearing in orthopaedic journals indexed in MEDLINE and Journal Citation Reports with a focus on LMICs or cohorts between 2009 and 2018. All articles describing research conducted in LMICs or research focused on applications to cohorts in LMIC(s) were included. Author affiliation, article characteristics, and impact factor were assessed for 1,573 articles. Logistic regression models created to identify predictors of LMIC authorship. RESULTS: We identified few studies published in indexed journals focused exclusively on LICs. Funded studies were less likely to have LMIC last authors. Compared with articles published in lower impact factor journals, those in journals with a higher impact factor were less likely to have a LMIC first or last author. The greater the number of countries represented per study, the less likely it had a LMIC first or last author. CONCLUSION: Our study highlights persistent disparities in authorship from LMICs in indexed orthopaedic journals.

Overall survival comparing laparoscopic to open surgery for right-sided colon cancer: propensity score inverse probability weighting population study.

BACKGROUND: This retrospective cohort study reports on overall survival and short-term complications, comparing laparoscopic to open resection for right-sided colon cancers. It is one of the largest studies in the field with generalizable population-level results. METHOD: This study on right sided colon cancers used prospectively collected administrative data linked to a death registry over 5 years from 2014 to 2018. Exclusion criteria were private patients, patients aged less than 10 years, synchronous and metachronous cancers. Propensity score weighting was used to balance cohorts and Cox proportional hazards regression was used to assess the hazard of death. In addition, logistic regression analysis was used to assess secondary outcomes. For completeness, unweighted data was similarly analysed. RESULTS: There were 3603 patients identified for the analysis: 1729 open patients and 1874 laparoscopic patients. Cox proportional hazards regression analysis of the weighted data showed no evidence of a statistically significant effect of laparoscopic surgery compared to open surgery on overall survival for right-sided colon cancers (HR 0.86, 95% CI 0.71-1.04, P = 0.112). The weighted data showed lower odds of prolonged length of stay, return to theatre and discharge destination other than home in the laparoscopic cohort compared to the open cohort. There was no difference in inpatient mortality. Unweighted results were similar. CONCLUSION: This study validates the use of laparoscopic surgery for right-sided colon cancer, showing similar long-term overall survival and inpatient mortality compared to open surgery. It is superior to open surgery for the short-term outcomes of LOS, return to theatre and discharge destination other than home.

Use of Temporary Abdominal Closure in Non-Trauma Surgery: A Cohort Study.

BACKGROUND: Damage control surgery in trauma is widely used but the evidence for the use of laparostomy in non-trauma abdominal emergencies is limited. This study aimed to characterise outcomes in emergency abdominal surgery by comparing laparostomy to one-stage laparotomy for patients of similar illness severity. METHODS: A retrospective study of adult patients requiring emergency abdominal surgery and post-operative intensive care stay was performed between 2016 and 2020 at a major Australian metropolitan hospital. Case selection was from a prospectively maintained database, and case notes were reviewed. Patients having delayed abdominal closure were compared with those having one-stage abdominal closure. The primary outcome was odds of in-hospital mortality. The secondary outcomes included intensive care unit length of stay (LOS), overall hospital LOS, definitive stoma rate and discharge destination. Multivariable logistic regression analysis was performed to adjust for potentially confounding variables. RESULTS: Two hundred and eighteen patients met inclusion criteria (80 laparostomy and 138 non-laparostomy). The most common indications for laparostomy were bowel ischaemia (41.3%), sepsis (26.3%) and physiological instability (22.5%). There was no evidence of difference in odds of in-hospital mortality between groups (adjusted OR = 1.67, CI: 0.85-3.28; p = 0.138). Patients requiring laparostomy had a slightly longer median ICU LOS (4 vs. 3 days; p < 0.001), similar median hospital LOS (19 vs. 14 days, p = 0.245) and similar discharge destination. There was no difference in stoma rate (35.0% vs. 35.5%). CONCLUSION: Compared with standard one-stage laparotomy, laparostomy resulted in similar odds of in-hospital mortality in emergency abdominal surgery patients requiring intensive care.

Socioeconomic disadvantage and its impact on colorectal cancer in Australia: a scoping review.

BACKGROUND: Social disparities in cancer survival have been demonstrated in Australia despite a universal healthcare insurance system. Colorectal cancer is common, and reasons for survival disparities related to socioeconomic status need to be investigated and addressed. The aim is to evaluate the current Australian literature concerning the impact of socioeconomic status on colorectal cancer survival and stage at presentation. METHODS: A systematic search of PUBMED, EMBASE, SCOPUS and Clarivate Web of Science databases from January 2010 to March 2022 was performed. Studies investigating the impact of socioeconomic status on colorectal stage at presentation or survival in Australia were included. Data were extracted on author, year of publication, state or territory of origin, patient population, other exposure variables, outcomes and findings and adjustments made. RESULTS: Of the 14 articles included, the patient populations examined varied in size from 207 to 100 000+ cases. Evidence that socioeconomic disadvantage was associated with poorer survival was demonstrated in eight of 12 studies. Evidence of effect on late stage at presentation was demonstrated in two of seven studies. Area-level measures were commonly used to assess socioeconomic status, with varying indices utilized. CONCLUSION: There is limited evidence that socioeconomic status is associated with late-stage at presentation. More studies provide evidence of an association between socioeconomic disadvantage and poorer survival, especially larger studies utilizing less clinically-detailed cancer registry data. Further investigation is required to analyse why socioeconomic disadvantage may be associated with poorer survival.

Novel PPP1R13L variant expands the phenotype of a rare cardiocutaneous syndrome.

PPP1R13L-associated cardiocutaneous syndrome is an autosomal recessive condition that presents with life-threatening dilated cardiomyopathy in early childhood, with or without features of inflammation on cardiac histology. There is also a variably expressed ectodermal phenotype.

Further characterization of Borjeson-Forssman-Lehmann syndrome in females due to de novo variants in PHF6.

While inherited hemizygous variants in PHF6 cause X-linked recessive Borjeson-Forssman-Lehmann syndrome (BFLS) in males, de novo heterozygous variants in females are associated with an overlapping but distinct phenotype, including moderate to severe intellectual disability, characteristic facial dysmorphism, dental, finger and toe anomalies, and linear skin pigmentation. By personal communication with colleagues, we assembled 11 additional females with BFLS due to variants in PHF6. We confirm the distinct phenotype to include variable intellectual disability, recognizable facial dysmorphism and other anomalies. We observed skewed X-inactivation in blood and streaky skin pigmentation compatible with functional mosaicism. Variants occurred de novo in 10 individuals, of whom one was only mildly affected and transmitted it to her more severely affected daughter. The mutational spectrum comprises a two-exon deletion, five truncating, one splice-site and three missense variants, the latter all located in the PHD2 domain and predicted to severely destabilize the domain structure. This observation supports the hypothesis of more severe variants in females contributing to gender-specific phenotypes in addition to or in combination with effects of X-inactivation and functional mosaicism. Therefore, our findings further delineate the clinical and mutational spectrum of female BFLS and provide further insights into possible genotype-phenotype correlations between females and males.

T-stage downstaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy is not associated with reduced recurrence after adjusting for tumour characteristics.

BACKGROUND AND OBJECTIVES: Prior studies examining prognostic outcomes of locally advanced rectal adenocarcinomas achieving a complete pathological response following neoadjuvant chemoradiotherapy (nCRT) did not adjust for adverse prognostic factors in multivariate analyses and account for magnetic resonance imaging tumour staging inaccuracy pre-nCRT. We aimed to clarify prognostic outcomes in mT3 rectal adenocarcinomas with ypT-downstaging post-nCRT in robust adjusted analyses. METHODS: Retrospective analysis of prospectively-collected clinical data from 528 mT3 rectal adenocarcinomas ≤12 cm from the anal verge, any N-stage, no metastases, post-nCRT following total mesorectal excision (TME). Recurrence outcomes (local and distant combined) of tumours with complete ypT-downstaging (ypT0) post-nCRT before TME compared with no ypT-downstaging (≥ypT3) were examined using multivariate Cox regression, adjusting for confounders and accounting for pre-nCRT mT3-staging inaccuracy using bootstrapping. RESULTS: Complete ypT-downstaging was achieved in of 17.6% tumours and correlated strongly with complete pathological response. Complete ypT-downstaging was not associated with reduced recurrence hazards compared with no ypT-downstaging (hazard ratio = 0.60; 95% confidence interval [CI]: 0.23-1.56; p = 0.30). Lymphovascular invasion (LVI) and ypN+ve increased recurrence hazards by 1.8-fold (95% CI: 1.10-2.79; p = 0.02) and 2.3-fold (95% CI: 1.48-3.54; p = 0.0002), respectively. CONCLUSION: Complete ypT-downstaging was not associated with reduced recurrence after adjusting for confounders and accounting for mT3-staging inaccuracy, even in the absence of adverse prognostic factors (ypN+, LVI).

Beyond Graft Survivl: A National Cohort Study Quantifying the Impact of Increasing Kidney Donor Profile Index on Recipient Outcomes 1 Year Post-transplantation.

Background: The reporting of a locally validated kidney donor profile index (KDPI) began in Australia in 2016. Across diverse populations, KDPI has demonstrated utility in predicting allograft survival and function. A metric that incorporates both elements may provide a more comprehensive picture of suboptimal recipient outcomes. Methods: A retrospective cohort study of adult kidney transplant recipients in Australia (January 2009 to December 2014) was conducted. Conventional recipient outcomes and a composite measure of suboptimal outcome (1-y allograft failure or estimated glomerular filtration rate [eGFR] <30 mL/min) were evaluated across KDPI intervals (KDPI quintiles and 5-point increments in the KDPI 81-100 cohort). The impact of increasing KDPI on allograft function (1-y eGFR) and a suboptimal outcome was explored using multivariable regression models, adjusting for potential confounding factors. Results: In 2923 donor kidneys eligible for analysis, median KDPI was 54 (interquartile range [IQR], 31-77), and Kidney Donor Risk Index was 1.39 (IQR, 1.03-1.67). The median 1-y eGFR was 52.74 mL/min (IQR, 40.79-66.41 mL/min). Compared with the first quintile reference group, progressive reductions in eGFR were observed with increasing KDPI and were maximal in the fifth quintile (adjusted ß-coefficient: -27.43 mL/min; 95% confidence interval, -29.44 to -25.42; P < 0.001). A suboptimal outcome was observed in 359 recipients (12.3%). The adjusted odds for this outcome increased across quintiles from a baseline of odds ratio of 1.00 (first quintile) to odds ratio of 11.68 (95% confidence interval, 6.33-21.54, P < 0.001) in the fifth quintile cohort. Conclusions: Increases in donor KDPI were associated with higher probabilities of a suboptimal outcome and poorer baseline allograft function, particularly in the KDPI > 80 cohort. These findings may inform pretransplant discussions with potential recipients of high-KDPI allografts.