Geology and Geomorphology of Jenolan Caves and the Surrounding Region

Detailed mapping by university students and staff since the 1980s has significantly elucidated previously poorly known stratigraphic and structural relationships in the Jenolan Caves region. Apart from andesite of ?Ordovician age, rocks west of the caves probably correlate with the lower Silurian Campbells Group. That succession is faulted against the Silurian (mid Wenlockian) Jenolan Caves Limestone, in which caves developed during several episodes from the late Palaeozoic. Immediately east of Jenolan Caves, siliciclastic sedimentary and volcaniclastic rocks with interbedded silicic lavas constitute the newly defined Inspiration Point Formation, correlated with the upper Silurian to Lower Devonian Mount Fairy Group. Several prominent marker units are recognised, including limestone previously correlated with the main Jenolan limestone belt. Extensive strike-slip and thrust faulting disrupts the sequence, but in general the entire Silurian succession youngs to the east, so that beds apparently steeply-dipping westerly are actually overturned. Further east, Upper Devonian Lambie Group siliciclastics unconformably overlie the Inspiration Point Formation and both are overlain unconformably by lower Permian conglomeratic facies. Carboniferous intrusions include the Hellgate Granite with associated felsite dykes. The regional geomorphology probably evolved from late Carboniferous–early Permian time, with ‘steps’ in the deep valleys indicating episodic periods of valley formation, possibly including Permian glaciation

Population-based observational study of acute pancreatitis in southern England

Introduction Acute pancreatitis is a common surgical emergency. Identifying variations in presentation, incidence and management may assist standardisation and optimisation of care. The objective of the study was to document the current incidence management and outcomes of acute pancreatitis against international guidelines, and to assess temporal trends over the past 20 years. Methods A prospective four-month audit of patients with acute pancreatitis was performed across the Wessex region. The Atlanta 2012 classifications were used to define cases, severity and complications. Outcomes were recorded using validated systems and correlated against guideline standards. Case ascertainment was validated with clinical coding and hospital episode statistics data. Results A total of 283 patient admissions with acute pancreatitis were identified. Aetiology included 153 gallstones (54%), 65 idiopathic (23%), 29 alcohol (10%), 9 endoscopic retrograde cholangiopancreatography (3%), 6 drug related (2%), 5 tumour (2%) and 16 other (6%). Compliance with guidelines had improved compared with our previous regional audit. Results were 6.5% mortality, 74% severity stratification, 23% idiopathic cases, 65% definitive treatment of gallstones within 2 weeks, 39% computed tomography within 6–10 days of severe pancreatitis presentation and 82% severe pancreatitis critical care admission. The Atlanta 2012 severity criteria significantly correlated with critical care stay, length of stay, development of complications and mortality (2% vs 6% vs 36%, P < 0.0001). Conclusions The incidence of acute pancreatitis in southern England has risen substantially. The Atlanta 2012 classification identifies patients with severe pancreatitis who have a high risk of fatal outcome. Acute pancreatitis management is seen to have evolved in keeping with new evidence and updated clinical guidelines

A Kernel to Exploit Informative Missingness in Multivariate Time Series from EHRs

A large fraction of the electronic health records (EHRs) consists of clinical measurements collected over time, such as lab tests and vital signs, which provide important information about a patient's health status. These sequences of clinical measurements are naturally represented as time series, characterized by multiple variables and large amounts of missing data, which complicate the analysis. In this work, we propose a novel kernel which is capable of exploiting both the information from the observed values as well the information hidden in the missing patterns in multivariate time series (MTS) originating e.g. from EHRs. The kernel, called TCK$_{IM}$, is designed using an ensemble learning strategy in which the base models are novel mixed mode Bayesian mixture models which can effectively exploit informative missingness without having to resort to imputation methods. Moreover, the ensemble approach ensures robustness to hyperparameters and therefore TCK$_{IM}$ is particularly well suited if there is a lack of labels - a known challenge in medical applications. Experiments on three real-world clinical datasets demonstrate the effectiveness of the proposed kernel.Comment: 2020 International Workshop on Health Intelligence, AAAI-20. arXiv admin note: text overlap with arXiv:1907.0525

Male fertility in cystic fibrosis.

Infertility rates among males with cystic fibrosis (CF) approximate 97%. No information is currently available within Ireland determining an understanding of fertility issues and the best methods of information provision to this specialized group. This study aimed to determine understanding and preferred approaches to information provision on fertility issues to Irish CF males. A Descriptive Study utilizing prospective coded questionnaires was mailed to a male CF cohort (n=50). Sections included demographics, fertility knowledge \u26 investigation. Response rate was 16/50 (32%). All were aware that CF affected their fertility. More than two-thirds (n=11) were able to provide explanations whilst only one-third (n=5) provided the correct explanation. Significant numbers stated thoughts of marriage and a future family. Half have discussed fertility with a healthcare professional (HCP). Mean age of discussion was 21.9 years. One third preferred an earlier discussion. The commonest first source for information was written material which was also the preferred source. Three-quarters requested further information preferring again, written material. Significant gaps in sex education of Irish CF males exist. Discussion should be initiated by HCPs and centre-directed written material devised to address deficiencies

The Roles of EDA2R in Ageing and Disease

Ageing is a complex biological process driven, in part, by inflammaging. Recent research identifies the ectodysplasin A2 receptor (EDA2R) as a key regulator of inflammaging and a novel biomarker of ageing, with its expression increasing with age across diverse tissues in humans and animal models. Elevated EDA2R gene expression is associated with accelerated ageing, cellular senescence, frailty, obesity, acne, radiation response and increased levels of inflammatory, renal, cardiac and vascular biomarkers. Similarly, elevated EDA2R protein levels, a critical component of the proteomic ageing clock, are associated with a wide range of conditions, including cardiovascular diseases, dementia, Parkinson's disease, mood disorders, post-traumatic stress disorder, various cancers, osteoarthritis, digestive diseases, diabetes, obesity, chronic obstructive pulmonary disease, ear and eye diseases, renal impairment, systemic autoimmune diseases, anaemia, bacterial infections, myositis, frailty, accelerated biological ageing, shorter telomere length, decreased healthspan and longevity, higher all-cause mortality and overall poor health. Beyond serving as a biomarker, EDA2R actively drives ageing, as its overexpression induces inflammation and tissue damage, whereas its inhibition mitigates these effects. Mechanistically, EDA2R activates non-canonical and canonical NF-κB signalling, promoting pro-inflammatory and catabolic processes that accelerate ageing phenotypes. Genetic variants of EDA2R are linked to alopecia, facial ageing, lipid profiles and prostate cancer. This review explores the structure and function of the EDA2R gene and protein, its role in tissue-specific ageing, and its therapeutic potential for multiple diseases. Although specific EDA2R antagonists are not yet available, interventions like calorie restriction, physical activity and specific supplements show promise in lowering EDA2R levels

Neuroprotective therapies in the NICU in term infants: present and future

Outcomes of neonatal encephalopathy (NE) have improved since the widespread implementation of therapeutic hypothermia (TH) in high-resource settings. While TH for NE in term and near-term infants has proven beneficial, 30–50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. There is therefore a critical need to find additional pharmacological and non-pharmacological interventions that improve the outcomes for these children. There are many potential candidates; however, it is unclear whether these interventions have additional benefits when used with TH. Although primary and delayed (secondary) brain injury starting in the latent phase after HI are major contributors to neurodisability, the very late evolving effects of tertiary brain injury likely require different interventions targeting neurorestoration. Clinical trials of seizure management and neuroprotection bundles are needed, in addition to current trials combining erythropoietin, stem cells, and melatonin with TH

Insights into pyroxene-dominated surfaces and implications for ongoing space exploration missions

Ungrouped achondrites are differentiated (melted) meteorites that do not fit into any known meteorite group because of their unusual mineralogies and/or oxygen isotopic compositions; their asteroidal or planetary origins are unknown. Two recently discovered samples, Northwest Africa 15915 (NWA 15915) and Ksar Ghilane 022 (KG 022), have mineral assemblages not previously identified in meteorites, consisting of iron-free silicates (including augite, enstatite, and olivine) and unusual sulphides (such as oldhamite). These samples offer the opportunity to probe the spectral properties of mineralogically distinct surfaces. NWA 15915 and KG 022 have oxygen isotopic compositions in the field of enstatite chondrites and aubrites, a near absence of spectral features in the visible and near-infrared, and a similar mineralogy to that which is expected for the surface of Mercury. While it is unlikely that the two meteorites are fragments of Mercury, they may be good analogs for Mercury's surface on a regional scale. ESA/JAXA's BepiColombo will provide an exceptional opportunity to compare the composition of differing mineralogical units on Mercury with samples such as NWA 15915 and KG 022

Risk of Bowel Obstruction in Patients Undergoing Neoadjuvant Chemotherapy for High-risk Colon Cancer: A Nested Case-control-matched Analysis of an International, Multicenter, Randomized Controlled Trial (FOxTROT)

OBJECTIVE: This study aimed to identify risk criteria available before the point of treatment initiation that can be used to stratify the risk of obstruction in patients undergoing neoadjuvant chemotherapy (NAC) for high-risk colon cancer. BACKGROUND: Global implementation of NAC for colon cancer, informed by the FOxTROT trial, may increase the risk of bowel obstruction. METHODS: A case-control study, nested within an international randomized controlled trial (FOxTROT; ClinicalTrials.gov: NCT00647530). Patients with high-risk operable colon cancer (radiologically staged T3-4 N0-2 M0) that were randomized to NAC and developed large bowel obstruction were identified. First, clinical outcomes were compared between patients receiving NAC in FOxTROT who did and did not develop obstruction. Second, obstructed patients (cases) were age-matched and sex-matched with patients who did not develop obstruction (controls) in a 1:3 ratio using random sampling. Bayesian conditional mixed-effects logistic regression modeling was used to explore clinical, radiologic, and pathologic features associated with obstruction. The absolute risk of obstruction based on the presence or absence of risk criteria was estimated for all patients receiving NAC. RESULTS: Of 1053 patients randomized in FOxTROT, 699 received NAC, of whom 30 (4.3%) developed obstruction. Patients underwent care in European hospitals including 88 UK, 7 Danish, and 3 Swedish centers. There was more open surgery (65.4% vs 38.0%, P=0.01) and a higher pR1 rate in obstructed patients (12.0% vs 3.8%, P=0.004), but otherwise comparable postoperative outcomes. In the case-control–matched Bayesian model, 2 independent risk criteria were identified: (1) obstructing disease on endoscopy and/or being unable to pass through the tumor [adjusted odds ratio: 9.09, 95% credible interval: 2.34–39.66] and stricturing disease on radiology or endoscopy (odds ratio: 7.18, 95% CI: 1.84–32.34). Three risk groups were defined according to the presence or absence of these criteria: 63.4% (443/698) of patients were at very low risk (10%). CONCLUSIONS: Safe selection for NAC for colon cancer can be informed by using 2 features that are available before treatment initiation and identifying a small number of patients with a high risk of preoperative obstruction

Magnetic resonance imaging (MRI) in rectal cancer: a comprehensive review

Magnetic resonance imaging (MRI) has established itself as the primary method for local staging in patients with rectal cancer. This is due to several factors, most importantly because of the ability to assess the status of circumferential resection margin. There are several newer developments being introduced continuously, such as diffusion-weighted imaging and imaging with 3 T. Assessment of loco-regional lymph nodes has also been investigated extensively using different approaches, but more work needs to be done. Finally, evaluation of tumours during or after preoperative treatment is becoming an everyday reality. All these new aspects prompt a review of the most recent advances and opinions. In this review, a comprehensive overview of the current status of MRI in the loco-regional assessment and management of rectal cancer is presented. The findings on MRI and their accuracy are reviewed based on the most up-to-date evidence. Optimisation of MRI acquisition and relevant regional anatomy are also presented, based on published literature and our own experience