Observation of ultracold atomic bubbles in orbital microgravity.

Substantial leaps in the understanding of quantum systems have been driven by exploring geometry, topology, dimensionality and interactions in ultracold atomic ensembles1-6. A system where atoms evolve while confined on an ellipsoidal surface represents a heretofore unexplored geometry and topology. Realizing an ultracold bubble-potentially Bose-Einstein condensed-relates to areas of interest including quantized-vortex flow constrained to a closed surface topology, collective modes and self-interference via bubble expansion7-17. Large ultracold bubbles, created by inflating smaller condensates, directly tie into Hubble-analogue expansion physics18-20. Here we report observations from the NASA Cold Atom Lab21 facility onboard the International Space Station of bubbles of ultracold atoms created using a radiofrequency-dressing protocol. We observe bubble configurations of varying size and initial temperature, and explore bubble thermodynamics, demonstrating substantial cooling associated with inflation. We achieve partial coverings of bubble traps greater than one millimetre in size with ultracold films of inferred few-micrometre thickness, and we observe the dynamics of shell structures projected into free-evolving harmonic confinement. The observations are among the first measurements made with ultracold atoms in space, using perpetual freefall to explore quantum systems that are prohibitively difficult to create on Earth. This work heralds future studies (in orbital microgravity) of the Bose-Einstein condensed bubble, the character of its excitations and the role of topology in its evolution.

"What will we do if we get infected?": An interview-based study of the COVID-19 pandemic and its effects on the health and safety of sex workers in the United States.

Emerging evidence suggests that sex workers face unique and profound risks arising from the COVID-19 pandemic. To illuminate the pandemic's effects on sex worker health and safety and identify intervention opportunities, from May-August 2020 in-depth interviews were conducted with a purposive sample of 15 sex workers, four service providers and two individuals who were both. Sampled sex workers included eight people of color, eight cisgender women, five cisgender men, three non-binary people, and one transgender woman. Using Conservation of Resources Theory to define impacts on sex worker resources and resulting health and safety implications, a deductive thematic analysis was conducted. Seven resources were threatened due to the pandemic: work opportunity, sex work venues, social support, health services, money, food, and housing. The loss of these resources was exacerbated by stigma - notably sex work criminalization - and significantly undermined health and safety by increasing food and housing instability, increasing risks of violence, and diminishing safer sex negotiation. Six resources were activated in response: social support, digital skills, health knowledge, non-sex work employment, money, and resilience. While social support had numerous benefits, investing digital skills and non-sex work employment were generally of limited impact. The pandemic's negative health and safety effects were most profound at the intersections of race, gender, class, and migration status. These findings suggest sex workers need urgent and ongoing support, with investments in social support and sex work decriminalization likely to have the greatest effects on health and safety relative to and beyond the COVID-19 pandemic.

Anxiety spectrum disorders are common in patients with orthostatic tremor.

BACKGROUND: Orthostatic Tremor (OT) is a rare movement disorder characterized by a sensation of unsteadiness while standing and associated with high frequency tremors. Patients with OT commonly report a fear of falling and significant limitations in everyday activities. The prevalence of psychiatric comorbidities in OT patients has not been well-studied. METHODS: Subjects were evaluated by trained psychiatry researchers using the Mini International Neuropsychiatric Interview (M.I.N.I.). The M.I.N.I is a validated screening tool for psychiatric disorders. A standardized history covering previous psychiatric symptoms and illnesses was also obtained. RESULTS: 29 OT subjects were evaluated. The mean age was 67.7 years with female preponderance (89.3%). The average disease symptom duration was 18.2 years. 58.6% of the subjects had seen a mental health professional during the course of their OT illness. 24.1% of the subjects had a past history of depression, and 10.3% reported a family history of any psychiatric condition. 37.9% of the subjects screened positive for agoraphobia. Two of 29 subjects (6.9%) were classified as having a current major depressive episode and one subject (3.4%) was at risk for suicide. CONCLUSIONS: Psychiatric comorbidities are highly prevalent in OT patients, especially anxiety-spectrum disorders. Further studies are needed to understand if psychiatric disorders appear as a secondary response to the patient's symptoms, or are a primary non-motor manifestation of OT.

Functional consequences of the first reported mutations of the proto-oncogene PTTG1IP/PBF.

Pituitary tumor-transforming gene 1-binding factor (PTTG1IP; PBF) is a multifunctional glycoprotein, which is overexpressed in a wide range of tumours, and significantly associated with poorer oncological outcomes, such as early tumour recurrence, distant metastasis, extramural vascular invasion and decreased disease-specific survival. PBF transforms NIH 3T3 fibroblasts and induces tumours in nude mice, while mice harbouring transgenic thyroidal PBF expression show hyperplasia and macrofollicular lesions. Our assumption that PBF becomes an oncogene purely through increased expression has been challenged by the recent report of mutations in PBF within the Catalogue of Somatic Mutations in Cancer (COSMIC) database. We therefore sought to determine whether the first 10 PBF missense substitutions in human cancer might be oncogenic. Anisomycin half-life studies revealed that most mutations were associated with reduced protein stability compared to wild-type (WT) PBF. Proliferation assays narrowed our interest to two mutational events which significantly altered cell turnover: C51R and R140W. C51R was mainly confined to the endoplasmic reticulum while R140W was apparent in the Golgi apparatus. Both C51R and R140W lost the capacity to induce cellular migration and significantly reduced cell invasion. Colony formation and soft agar assays demonstrated that, in contrast to WT PBF, both mutants were unable to elicit significant colony formation or anchorage-independent growth. However, C51R and R140W retained the ability to repress radioiodide uptake, a functional hallmark of PBF. Our data reveal new insight into PBF function and confirm that, rather than being oncogenic, mutations in PBF are likely to be passenger effects, with overexpression of PBF the more important aetiological event in human cancer.

Elevated PTTG and PBF predicts poor patient outcome and modulates DNA damage response genes in thyroid cancer.

The proto-oncogene PTTG and its binding partner PBF have been widely studied in multiple cancer types, particularly thyroid and colorectal, but their combined role in tumourigenesis is uncharacterised. Here, we show for the first time that together PTTG and PBF significantly modulate DNA damage response (DDR) genes, including p53 target genes, required to maintain genomic integrity in thyroid cells. Critically, DDR genes were extensively repressed in primary thyrocytes from a bitransgenic murine model (Bi-Tg) of thyroid-specific PBF and PTTG overexpression. Irradiation exposure to amplify p53 levels further induced significant repression of DDR genes in Bi-Tg thyrocytes (P=2.4 × 10-4) compared with either PBF- (P=1.5 × 10-3) or PTTG-expressing thyrocytes (P=NS). Consistent with this, genetic instability was greatest in Bi-Tg thyrocytes with a mean genetic instability (GI) index of 35.8±2.6%, as well as significant induction of gross chromosomal aberrations in thyroidal TPC-1 cells following overexpression of PBF and PTTG. We extended our findings to human thyroid cancer using TCGA data sets (n=322) and found striking correlations with PBF and PTTG expression in well-characterised DDR gene panel RNA-seq data. In addition, genetic associations and transient transfection identified PBF as a downstream target of the receptor tyrosine kinase-BRAF signalling pathway, emphasising a role for PBF as a novel component in a pathway well described to drive neoplastic growth. We also showed that overall survival (P=1.91 × 10-5) and disease-free survival (P=4.9 × 10-5) was poorer for TCGA patients with elevated tumoural PBF/PTTG expression and mutationally activated BRAF. Together our findings indicate that PBF and PTTG have a critical role in promoting thyroid cancer that is predictive of poorer patient outcome.

Survival following operative management of gastric linitis plastica compared with non-operative management.

INTRODUCTION Linitis plastica (LP) is a particular subtype of diffuse gastric cancer and is thought to have a very poor prognosis. The operative approach in patients with LP has historically been questioned because of the poor outcomes. The aim of this study was to determine the current outcomes in LP patients who undergo radical resection. METHODS Patients with a new diagnosis of diffuse gastric adenocarcinoma between 2006 and 2010 were identified from a regional pathology database. LP was diagnosed based on histological, radiological and endoscopic findings. The patients' health records were analysed retrospectively and mortality data obtained from a regional cancer registry. The primary outcome assessed was overall survival. RESULTS Overall, 273 patients with diffuse gastric cancer were identified; 54 of these were diagnosed with LP. In the LP cohort, 17 patients underwent resection compared with 95 of the 219 patients in the non-LP group. The median survival following resection in patients with LP was 16.7 months (95% confidence interval [CI]: 8.3-25.1) while in LP patients who did not have surgery it was 3.6 months (95% CI: 2.2-4.9 months) (p<0.001). There was no significant difference in survival following resection between those with LP and those with non-LP diffuse gastric adenocarcinoma (median: 23.9 months, 95% CI: 15.8-32.1 months) (p=0.331). CONCLUSIONS Survival following resection in patients with LP is not significantly different to that in those with non-LP diffuse gastric cancer. A preoperative diagnosis of LP should not be a reason for denying radical treatment and such individuals should be managed in the same way as any other patient with diffuse gastric cancer.

The current role of staging laparoscopy in oesophagogastric cancer.

INTRODUCTION: Oesophagogastric cancers are known to spread rapidly to locoregional lymph nodes and by transcoelomic spread to the peritoneal cavity. Staging laparoscopy combined with peritoneal cytology can detect advanced disease that may not be apparent on other staging investigations. The aim of this study was to determine the current value of staging laparoscopy and peritoneal cytology in light of the ubiquitous use of computed tomography in all oesophagogastric cancers and the addition of positron emission tomography in oesophageal cancer. METHODS: All patients undergoing staging laparoscopy for distal oesophageal or gastric cancer between March 2007 and August 2013 were identified from a prospectively maintained database. Demographic details, preoperative staging, staging laparoscopy findings, cytology and histopathology results were analysed. RESULTS: A total of 317 patients were identified: 159 (50.1%) had gastric adenocarcinoma, 136 (43.0%) oesophageal adenocarcinoma and 22 (6.9%) oesophageal squamous carcinoma. Staging laparoscopy revealed macroscopic metastases in 36 patients (22.6%) with gastric adenocarcinoma and 16 patients (11.8%) with oesophageal adenocarcinoma. Positive peritoneal cytology in the absence of macroscopic peritoneal metastases was identified in a further five patients with gastric adenocarcinoma and six patients with oesophageal adenocarcinoma. There was no significant difference in survival between patients with macroscopic peritoneal disease and those with positive peritoneal cytology (p=0.219). CONCLUSIONS: Staging laparoscopy and peritoneal cytology should be performed routinely in the staging of distal oesophageal and gastric cancers where other investigations indicate resectability. Currently, in our opinion, patients with positive peritoneal cytology should not be treated with curative intent.

Deprivation and ethnicity impact on diabetes control and use of treatment regimen.

AIMS: Deprivation and/or ethnicity impact on care delivery. We have assessed how these factors influence diabetes care in a paediatric clinic. METHODS: We related access to care [type of insulin treatment regimen-twice daily, multiple daily injections and insulin pump therapy (continuous subcutaneous insulin infusion)], measures of care process (HbA(1c)) and an approximate measure of satisfaction with the service (clinic attendance rate) in 325 (170 male) children and young people with Type 1 diabetes (mean age 10.6 years, mean duration of diabetes of 4.5 years), with indices of deprivation and ethnicity. RESULTS: Of the 325 children and young people, 2.7% received twice-daily insulin, 48.4% multiple daily injections and 48.9% continuous subcutaneous insulin infusion. Median clinic HbA(1c) was 62 mmol/mol (7.8%) and those receiving the insulin pump therapy had the lowest HbA(1c). Four ethnic groups were represented; White British 81.6%, Asian non-Indian 6.5%, African 8.1% and Asian Indian 3.8%. Mean deprivation score was 21.06. White British and Asian Indian groups were more likely to receive insulin pump therapy (χ(2) = 50.3; P < 0.001). Attendance rates were 94.1% and did not differ across ethnic groups. Deprivation was related to ethnicity and HbA(1c) (R(2) = 0.02; P = 0.02). There was no relationship between clinic attendance and deprivation. Insulin regimen and ethnicity were associated with HbA(1c) (R(2) = 0.096; P < 0.001). Similar findings were obtained when analysis was confined to the White British population. CONCLUSIONS: These data suggest that deprivation and ethnicity influence diabetes control and how intensive insulin therapy is utilized. A better consideration of the needs of different ethnic groups is required to ensure equitable care delivery in paediatric diabetes.

Frequency stability of a dual-mode whispering gallery mode optical reference cavity.

We report an investigation of laser frequency stabilization using a whispering gallery mode resonator that is temperature stabilized by a dual-mode technique. This dual-mode technique has yielded mode volume temperature instabilities at the nK level, suggesting that high frequency stability may also be reached. Here, we experimentally and theoretically investigate the dynamics of such a system and the important factors affecting the achievable frequency stability. We calculate that the dual-mode technique can reduce the effective fractional temperature coefficient of the reference system to 3.6×10⁻8 K⁻¹ within the temperature feedback bandwidth. We demonstrate a 1560 nm laser stabilized to 1.3×10⁻¹² at 1 s and 1.1×10⁻¹° at 1000 s, corresponding to a long-term drift of 21 kHz/hr.

Temperature measurement and stabilization in a birefringent whispering gallery mode resonator.

Temperature measurement with nano-Kelvin resolution is demonstrated at room temperature, based on the thermal dependence of an optical crystal anisotropy in a high quality whispering gallery mode resonator. As the resonator's TE and TM modes frequencies have different temperature coefficients, their differential shift provides a sensitive measurement of the temperature variation, which is used for active stabilization of the temperature.

A rare pathological trinity: an appendiceal ectopic pregnancy, acute appendicitis and a carcinoid tumour.

BACKGROUND: We present a case of a 27-year-old woman who was found to have an appendiceal ectopic pregnancy, a carcinoid tumour of the appendix and acute appendicitis existing concurrently. This triad of pathology has never been reported previously. CONCLUSIONS: This case highlights the importance of performing a pregnancy test in all women of childbearing age presenting with acute abdominal pain and also the need to consider other diagnoses that may mimic or present concurrently with acute appendicitis.

Contribution of variant alleles of ABCB11 to susceptibility to intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) has a complex aetiology with a significant genetic component. ABCB11 encodes the bile salt export pump (BSEP); mutations cause a spectrum of cholestatic disease, and are implicated in the aetiology of ICP. METHODS: ABCB11 variation in ICP was investigated by screening for five mutant alleles (E297G, D482G, N591S, D676Y and G855R) and the V444A polymorphism (c.1331T>C, rs2287622) in two ICP cohorts (n = 333 UK, n = 158 continental Europe), and controls (n = 261) for V444A. PCR primers were used to amplify and sequence patient and control DNA. The molecular basis for the observed phenotypes was investigated in silico by analysing the equivalent residues in the structure of the homologous bacterial transporter Sav1866. RESULTS: E297G was observed four times and D482G once. N591S was present in two patients; D676Y and G855R were not observed. The V444A polymorphism was associated with ICP (allelic analysis for C vs T: OR 1.7 (95% CI 1.4 to 2.1, p<0.001)). In addition, CC homozygotes were more likely to have ICP than TT homozygotes: OR 2.8 (95% CI 1.7 to 4.4 p<0.0001). Structural analyses suggest that E297G and D482G destabilize the protein fold of BSEP. The molecular basis of V444A and N591S was not apparent from the Sav1866 structure. CONCLUSIONS: Heterozygosity for the common ABCB11 mutations accounts for 1% of European ICP cases; these two mutants probably reduce the folding efficiency of BSEP. N591S is a recurrent mutation; however, the mechanism may be independent of protein stability or function. The V444A polymorphism is a significant risk factor for ICP in this population.

Endoscopically assisted minimally invasive surgery for gallstones.

BACKGROUND: We present a case report of Bouveret syndrome followed by a review of the recent literature regarding the management of this condition. Bouveret syndrome is a form of gastric outlet obstruction secondary to a gallstone which has eroded through the gallbladder into the duodenum. It is an uncommon variant of gallstone ileus. Endoscopic methods have been described to extract the stone from the duodenum. METHODS: This is a case of an 85-year-old female patient who presented with a 1-week history of nausea, intermittent bilious vomiting and anorexia. Imaging confirmed the diagnosis of Bouveret syndrome caused by two large gallstones. Conventional endoscopic methods successfully extracted the impacted stones from the duodenum into the stomach but were unable to extract the stones from the stomach. A mini-transverse laparotomy and gastrotomy were performed to finally extract the stones.

The function of the midtarsal joint: a review of the literature.

The midtarsal joint (MTJt) consists of the combined articulations of the talonavicular and calcaneocuboid joints and represents the functional articulation between the rearfoot (talus and calcaneus) and the midfoot (navicular and cuboid). The movement of the transverse tarsal region has been described as a segment rotating around two distinct axes of the MTJt; the longitudinal and the oblique. Recent research has suggested that the two axes model of the MTJt is a theory of convenience to explain clinical observation, and that the MTJt moves in a more complex manner. It has been hypothesised that the MTJt has one triplanar axis of motion, so there remains the need to investigate the practical application of this understanding in terms of how this motion affects the MTJt in gait and the implications this may have on podiatric treatment.

Pneumobilia following blunt abdominal trauma.

BACKGROUND: Pneumobilia is the presence of gas within the biliary tree. It is an important diagnostic sign in spontaneous biliary enteric fistulae, classically in gallstone ileus. There are a number of other causes including surgically created biliary enteric fistula, instrumentation of the bile duct at endoscopic retrograde cholangiopancreatography, emphysematous cholecystitis and pyogenic cholangitis. Pneumobilia has also been reported following blunt abdominal trauma. The significance of isolated pneumobilia following abdominal trauma has not been conclusively established. METHODS: We present a patient with traumatic pneumobilia following blunt trauma to the abdomen which was managed conservatively. CONCLUSION: Pneumobilia following blunt abdominal trauma is not an absolute indication for laparotomy.

Mutations in bile salt export pump (ABCB11) in two children with progressive familial intrahepatic cholestasis and cholangiocarcinoma.

Fatal peripheral cholangiocarcinoma developed in 2 girls with progressive familial intrahepatic cholestasis, ABCB11 mutations, and absent bile salt export pump (BSEP) expression. BSEP deficiency may cause cholangiocarcinoma through bile-composition shifts or bile-acid damage within cells capable of hepatocytic/cholangiocytic differentiation. This observation suggests the need for hepatobiliary-malignancy surveillance and early consideration for liver transplantation.

A rotenone-sensitive site and H2O2 are key components of hypoxia-sensing in neonatal rat adrenomedullary chromaffin cells.

In the perinatal period, adrenomedullary chromaffin cells (AMC) directly sense PO2 and secrete catecholamines during hypoxic stress, and this response is lost in juvenile ( approximately 2 week-old) chromaffin cells following postnatal innervation. Here we tested the hypothesis that a rotenone-sensitive O2-sensor and ROS are involved in the hypoxic response of AMC cultured from neonatal and juvenile rats. In whole-cell recordings, hypoxia (PO2=5-15 mm Hg) inhibited outward current in neonatal AMC; this response was reversed by exogenous H2O2 and mimicked and occluded by intracellular catalase (1000 units/ml), as well as the antioxidants, N-acetyl-L-cysteine (NAC; 50 microM) and Trolox (200 microM). Acute hypoxia decreased ROS levels and stimulated ATP secretion in these cells, as measured by luminol and luciferin-luciferase chemiluminescence, respectively. Of several mitochondrial electron transport chain (ETC) inhibitors tested, only rotenone, a complex I blocker, mimicked and occluded the effects of hypoxia on outward current, cellular ROS, and ATP secretion. Succinate donors, which act as complex II substrates, reversed the effects of hypoxia and rotenone in neonatal AMC. In contrast, in hypoxia-insensitive juvenile AMC, neither NAC nor rotenone stimulated ATP secretion though they both caused a decrease in ROS levels. We propose that O2-sensing by neonatal AMC is mediated by decreased ROS generation via a rotenone-sensitive site that is coupled to outward current inhibition and secretion. Interestingly, juvenile AMC display at least two modifications, i.e. an uncoupling of the O2-sensor from ROS regulation, and an apparent insensitivity of outward current to decreased ROS.

Spinor dynamics-driven formation of a dual-beam atom laser.

We demonstrate a novel dual-beam atom laser formed by outcoupling oppositely polarized components of an all-optical F = 1 spinor Bose-Einstein condensate whose Zeeman sublevel populations have been coherently evolved through spin dynamics. The condensate is formed through all-optical means using a single-beam running-wave dipole trap. We create a condensate in the magnetic field-insensitive m(F) = 0 state, and drive coherent spin-mixing evolution through adiabatic compression of the initially weak trap. Such dual beams, number-correlated through the angular momentum-conserving reaction 2m(0) ?m(+1) +m(-1), have been proposed as tools to explore entanglement and squeezing in Bose-Einstein condensates, and have potential use in precision phase measurements.

Congenital multifocal inflammatory pseudotumor: a case report.

Inflammatory pseudotumor is an uncommon benign tumor found in various sites throughout the body. The etiology is unclear with evidence to support both neoplastic and infective processes. The authors present a case with several unique features. It represents the first reported case detected antenatally. The tumor was found separately within the abdomen and thorax. The thoracic component of the tumor was managed without resection or ablative treatment but showed spontaneous regression.

Acid-secreting rectal duplication cyst with associated peptic ulcer eroding through the anal sphincters.

A rectal duplication cyst with heterotopic gastric mucosa that resulted in a trans-sphincteric peptic ulcer on the opposite wall of the anus of a child is described. The management and outcome and a review of the literature is presented.