The COSMIC Bubble Helmet: A Non-Invasive Positive Pressure Ventilation System for COVID-19.

Goal: COSMIC Medical, a Vancouver-based open-source volunteer initiative, has designed an accessible, affordable, and aerosol-confining non-invasive positive-pressure ventilator (NIPPV) device, known as the COSMIC Bubble Helmet (CBH). This device is intended for COVID-19 patients with mild-to-moderate acute respiratory distress syndrome. System Design: CBH is composed of thermoplastic polyurethane, which creates a flexible neck seal and transparent hood. This device can be connected to wall oxygen, NIPPVs including Continuous Positive Airway Pressure and Bi-level Positive Airway Pressure, and mechanical ventilators. Discussion: Justification of CBH design components relied on several factors, predominantly the safety and comfort of patients and healthcare providers. Conclusion: CBH has implications within and outside of the pandemic, as an alternative to invasive mechanical ventilation methods. We have experimentally verified that CBH is effective in minimizing aerosolization risks and performs at specified clinical requirements.

Novel Strongly Spin-Orbit Coupled Quantum Dimer Magnet: Yb_{2}Si_{2}O_{7}.

The quantum dimer magnet (QDM) is the canonical example of quantum magnetism. The QDM state consists of entangled nearest-neighbor spin dimers and often exhibits a field-induced triplon Bose-Einstein condensate (BEC) phase. We report on a new QDM in the strongly spin-orbit coupled, distorted honeycomb-lattice material Yb_{2}Si_{2}O_{7}. Our single crystal neutron scattering, specific heat, and ultrasound velocity measurements reveal a gapped singlet ground state at zero field with sharp, dispersive excitations. We find a field-induced magnetically ordered phase reminiscent of a BEC phase, with exceptionally low critical fields of H_{c1}∼0.4 and H_{c2}∼1.4 T. Using inelastic neutron scattering in an applied magnetic field we observe a Goldstone mode (gapless to within δE=0.037 meV) that persists throughout the entire field-induced magnetically ordered phase, suggestive of the spontaneous breaking of U(1) symmetry expected for a triplon BEC. However, in contrast to other well-known cases of this phase, the high-field (µ_{0}H≥1.2 T) part of the phase diagram in Yb_{2}Si_{2}O_{7} is interrupted by an unusual regime signaled by a change in the field dependence of the ultrasound velocity and magnetization, as well as the disappearance of a sharp anomaly in the specific heat. These measurements raise the question of how anisotropy in strongly spin-orbit coupled materials modifies the field induced phases of QDMs.

Feasibility of a bone and soft tissue chimeric anterolateral thigh free flap? Anatomic study and report of two cases for oral cavity reconstruction.

The anterolateral thigh flap (ALT) is a workhorse for a spectrum of reconstructive problems including head and neck defects. Its versatility as a chimeric flap employing a variety of soft tissues with a robust pedicle is useful for three-dimensional defects. The authors investigated the anatomical relationship between the vascular supply to the ALT and anterior femur. We studied 16 fresh cadaver limbs to identify the typical branching patterns to the femur off the descending branch of the lateral circumflex femoral artery. These patterns can facilitate dissection of this type of chimeric ALT. The authors have integrated a bone component of vascularised femur in this flap off the lateral circumflex femoral artery system to address oral cancer defects in two patients. A retrospective review of these cases correlating with the anatomic study was undertaken. Both patients had recurrent disease with limited donor site options. Both had extensive floor of mouth and tongue defects as well as small mandible defects of 2 cm. Both went on to heal at the donor and recipient sites at 32 months' follow-up.

The Financial Costs, Behaviour and Psychology of Obesity: A One Health Analysis.

People who are overweight or have obesity are estimated to comprise 30% of the global population and up to 59% of companion dogs and cats are estimated to be above their optimal body weight. The prevalence of human and companion obesity is increasing. The direct and indirect costs of obesity and associated comorbidities are significant for human and veterinary healthcare. There are numerous similarities between obesity in people and companion animals, likely related to the shared environmental and lifestyle elements of this multifactorial disease. While the study of human obesity is relatively robust, research conducted in pets is generally limited to small studies, studies with cross-sectional designs or reports that have yet to be replicated. Greater understanding of human obesity may elucidate some of the factors driving the more recent rise in pet obesity. In particular, there are overlapping features of obesity in children and pets that are, in part, related to dependency on their 'parents' for care and feeding. When feeding is used in a coercive and controlling fashion, it may lead to undesirable feeding behaviour and increase the risk for obesity. A 'responsive parenting' intervention teaches parents to respond appropriately to hunger-satiety cues and to recognize and respond to others' distress. Such interventions may impact on childhood overweight and obesity and have the potential to be adapted for use with companion animals. Social behaviour towards people with obesity or owners of pets with obesity is often driven by beliefs about the cause of the obesity. Educating healthcare professionals and the public about the multifactorial nature of this complex disease process is a fundamental step in reducing the bias and stigma associated with obesity. Children living in low-income households have particularly high rates of obesity and as household income falls, rates of obesity also rise in pets and their owners. There are risk regulators (i.e. dynamic components of interconnected systems that influence obesity-related behaviours) and internal factors (i.e. biological determinants of obesity) that may influence the development of both childhood and pet obesity, and poverty may intersect with these variables to exacerbate obesity in low-income environments. This review discusses the costs, behaviours and psychology related to obesity in people and pets, and also proposes potential techniques that can be considered for prevention and treatment of this disease in pets. A 'One Health' approach to obesity suggests that an understanding of human obesity may elucidate some of the factors driving the more recent rise in pet obesity.

The WHO application of ICD-10 to deaths during the perinatal period (ICD-PM): results from pilot database testing in South Africa and United Kingdom.

OBJECTIVE: To apply the World Health Organization (WHO) Application of the International Classification of Diseases, tenth revision (ICD-10) to deaths during the perinatal period: ICD-Perinatal Mortality (ICD-PM) to existing perinatal death databases. DESIGN: Retrospective application of ICD-PM. SETTING: South Africa, UK. POPULATION: Perinatal death databases. METHODS: Deaths were grouped according to timing of death and then by the ICD-PM cause of death. The main maternal condition at the time of perinatal death was assigned to each case. MAIN OUTCOME MEASURES: Causes of perinatal mortality, associated maternal conditions. RESULTS: In South Africa 344/689 (50%) deaths occurred antepartum, 11% (n = 74) intrapartum and 39% (n = 271) in the early neonatal period. In the UK 4377/9067 (48.3%) deaths occurred antepartum, with 457 (5%) intrapartum and 4233 (46.7%) in the neonatal period. Antepartum deaths were due to unspecified causes (59%), chromosomal abnormalities (21%) or problems related to fetal growth (14%). Intrapartum deaths followed acute intrapartum events (69%); neonatal deaths followed consequences of low birthweight/ prematurity (31%), chromosomal abnormalities (26%), or unspecified causes in healthy mothers (25%). Mothers were often healthy; 53%, 38% and 45% in the antepartum, intrapartum and neonatal death groups, respectively. Where there was a maternal condition, it was most often maternal medical conditions, and complications of placenta, cord and membranes. CONCLUSIONS: The ICD-PM can be a globally applicable perinatal death classification system that emphasises the need for a focus on the mother-baby dyad as we move beyond 2015. TWEETABLE ABSTRACT: ICD-PM is a global system that classifies perinatal deaths and links them to maternal conditions.

Application of ICD-PM to preterm-related neonatal deaths in South Africa and United Kingdom.

OBJECTIVE: We explore preterm-related neonatal deaths using the WHO application of the International Classification of Disease (ICD-10) to deaths during the perinatal period: ICD-PM as an informative case study, where ICD-PM can improve data use to guide clinical practice and programmatic decision-making. DESIGN: Retrospective application of ICD-PM. SETTING: South Africa, and the UK. POPULATION: Perinatal death databases. METHODS: Descriptive analysis of neonatal deaths and maternal conditions present. MAIN OUTCOME MEASURES: Causes of preterm neonatal mortality and associated maternal conditions. RESULTS: We included 98 term and 173 preterm early neonatal deaths from South Africa, and 956 term and 3248 preterm neonatal deaths from the UK. In the South African data set, the main causes of death were respiratory/cardiovascular disorders (34.7%), low birthweight/prematurity (29.2%), and disorders of cerebral status (25.5%). Amongst preterm deaths, low birthweight/prematurity (43.9%) and respiratory/cardiovascular disorders (32.4%) were the leading causes. In the data set from the UK, the leading causes of death were low birthweight/prematurity (31.6%), congenital abnormalities (27.4%), and deaths of unspecified cause (26.1%). In the preterm deaths, the leading causes were low birthweight/prematurity (40.9%) and deaths of unspecified cause (29.6%). In South Africa, 61% of preterm deaths resulted from the maternal condition of preterm spontaneous labour. Among the preterm deaths in the data set from the UK, no maternal condition was present in 36%, followed by complications of placenta, cord, and membranes (23%), and other complications of labour and delivery (22%). CONCLUSIONS: ICD-PM can be used to appraise the maternal and newborn conditions contributing to preterm deaths, and can inform practice. TWEETABLE ABSTRACT: ICD-PM can be used to appraise maternal and newborn contributors to preterm deaths to improve quality of care.

Optimising the International Classification of Diseases to identify the maternal condition in the case of perinatal death.

OBJECTIVE: The WHO application of the tenth edition of the International Classification of Diseases (ICD-10) to deaths during the perinatal period (ICD Perinatal Mortality, ICD-PM) captures the essential characteristics of the mother-baby dyad that contribute to perinatal deaths. We compare the capture of maternal conditions in the existing ICD-PM with the maternal codes from the WHO application of ICD-10 to deaths during pregnancy, childbirth, and the puerperium (ICD Maternal Mortality, ICD-MM) to explore potential benefits in the quality of data received. DESIGN: Retrospective application of ICD-PM. SETTING: South Africa and the UK. POPULATION: Perinatal death databases. METHODS: The maternal conditions were classified using the ICD-PM groupings for maternal condition in perinatal death, and then mapped to the ICD-MM groupings of maternal conditions. MAIN OUTCOME MEASURES: Main maternal conditions in perinatal deaths. RESULTS: We reviewed 9661 perinatal deaths. The largest group (4766 cases, 49.3%) in both classifications captures deaths where there was no contributing maternal condition. Each of the other ICD-PM groups map to between three and six ICD-MM groups. If the cases in each ICD-PM group are re-coded using ICD-MM, each group becomes multiple, more specific groups. For example, the 712 cases in group M4 in ICD-PM become 14 different and more specific main disease categories when the ICD-MM is applied instead. CONCLUSIONS: As we move towards ICD-11, the use of the more specific, applicable, and relevant codes outlined in ICD-MM for both maternal deaths and the maternal condition at the time of a perinatal death would be preferable, and would provide important additional information about perinatal deaths. TWEETABLE ABSTRACT: Improving the capture of maternal conditions in perinatal deaths provides important actionable information.

Block Magnetic Excitations in the Orbitally Selective Mott Insulator BaFe_{2}Se_{3}.

Iron pnictides and selenides display a variety of unusual magnetic phases originating from the interplay between electronic, orbital, and lattice degrees of freedom. Using powder inelastic neutron scattering on the two-leg ladder BaFe_{2}Se_{3}, we fully characterize the static and dynamic spin correlations associated with the Fe_{4} block state, an exotic magnetic ground state observed in this low-dimensional magnet and in Rb_{0.89}Fe_{1.58}Se_{2}. All the magnetic excitations of the Fe_{4} block state predicted by an effective Heisenberg model with localized spins are observed below 300 meV and quantitatively reproduced. However, the data only account for 16(3)µ_{B}^{2} per Fe^{2+}, approximatively 2/3 of the total spectral weight expected for localized S=2 moments. Our results highlight how orbital degrees of freedom in iron-based magnets can conspire to stabilize an exotic magnetic state.

Experiences with maternal and perinatal death reviews in the UK--the MBRRACE-UK programme.

Established in 1952, the programme of surveillance and Confidential Enquiries into Maternal Deaths in the UK is the longest running such programme worldwide. Although more recently instituted, surveillance and confidential enquiries into perinatal deaths are also now well established nationally. Recent changes to funding and commissioning of the Enquiries have enabled both a reinvigoration of the processes and improvements to the methodology with an increased frequency of future reporting. Close engagement with stakeholders and a regulator requirement for doctors to participate have both supported the impetus for involvement of all professionals leading to greater potential for improved quality of care for women and babies.

Report of a Royal College of Physicians and National Institute for Health Research workshop - developing research capacity to ensure successful study development and delivery.

The landscape and opportunities for clinical research have changed significantly following the creation of the National Institute for Health Research (NIHR) in 2006. This article describes the scale and impact of the NIHR network infrastructure for clinical research and identifies areas for future development in partnership with the National Health Service (NHS), clinicians and research funders.

CD44 promotes Kras-dependent lung adenocarcinoma.

Kras-induced non-small-cell lung adenocarcinoma is the major subtype of lung cancers and is associated with poor prognosis. Using a lung cancer mouse model that expresses a cre-mediated KrasG12D mutant, we identified a critical role for the cell surface molecule CD44 in mediating cell proliferation downstream of oncogenic Kras signaling. The deletion of CD44 attenuates lung adenocarcinoma formation and prolongs the survival of these mice. Mechanistically, CD44 is required for the activation of Kras-mediated signaling through the mitogen-activated protein kinase (MAPK) pathway and thus promotes tumor cell proliferation. Together, these results reveal an unrecognized role for CD44 in oncogenic Kras-induced lung adenocarcinoma and suggest that targeting CD44 could be an effective strategy for halting Kras-dependent carcinomas.

Possible valence-bond condensation in the frustrated cluster magnet LiZn2Mo3O8.

The emergence of complex electronic behaviour from simple ingredients has resulted in the discovery of numerous states of matter. Many examples are found in systems exhibiting geometric magnetic frustration, which prevents simultaneous satisfaction of all magnetic interactions. This frustration gives rise to complex magnetic properties such as chiral spin structures, orbitally driven magnetism, spin-ice behaviour exhibiting Dirac strings with magnetic monopoles, valence-bond solids and spin liquids. Here we report the synthesis and characterization of LiZn(2)Mo(3)O(8), a geometrically frustrated antiferromagnet in which the magnetic moments are localized on small transition-metal clusters rather than individual ions. By doing so, first-order Jahn-Teller instabilities and orbital ordering are prevented, allowing the strongly interacting magnetic clusters in LiZn(2)Mo(3)O(8) to probably give rise to an exotic condensed valence-bond ground state reminiscent of the proposed resonating valence-bond state. Our results also link magnetism on clusters to geometric magnetic frustration in extended solids, demonstrating a new approach for unparalleled chemical control and tunability in the search for collective, emergent electronic states of matter.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults characterized by high viral genome load within circulating natural killer cells.

Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive disease usually encountered in the context of primary EBV infection. In most analyzed cases, EBV has been found predominantly in T cells. We describe the novel finding of high EBV genome numbers within circulating natural killer cells in adult patients with EBV-HLH.

Choice and birth method: mixed-method study of caesarean delivery for maternal request.

OBJECTIVE: To explore whether women view decision-making surrounding vaginal or caesarean birth as their choice. DESIGN: Longitudinal cohort study utilising quantitative (questionnaire, routinely collected data) and qualitative (in-depth interviews) methods simultaneously. SETTING: A large hospital providing National Health Service maternity care in the UK. SAMPLE: Four-hundred and fifty-four primigravid women. METHODS: Women completed up to three questionnaires between their antenatal booking appointment and delivery. Amongst these women, 153 were interviewed at least once during pregnancy (between 24 and 36 weeks) and/or after 12 moths after birth. Data were also obtained from women's hospital delivery records. Descriptive statistical analysis was performed (survey and delivery data). Interview data were analysed using a seven-stage sequential form of qualitative analysis. RESULTS: Whilst many women supported the principle of choice, they identified how, in practice their autonomy was limited by individual circumstance and available care provision. All women felt that concerns about their baby's or their own health should take precedence over personal preference. Moreover, expressing a preference for either vaginal or caesarean birth was inherently problematic as choice until the time of delivery was neither static nor final. Women did not have autonomous choice over their actual birth method, but neither did they necessarily want it. CONCLUSIONS: The results of this large exploratory study suggest that choice may not be the best concept through which to approach the current arrangements for birth in the UK. Moreover, they challenge the notion of choice that currently prevails in international debates about caesarean delivery for maternal request.

Interventions for twin-twin transfusion syndrome: a Cochrane review.

We performed a Cochrane review to assess which of the treatments for twin-twin transfusion syndrome (TTTS) improves fetal, childhood and maternal outcomes. This article represents a version of the review which includes additional data to the published version. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2007) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, October 2007) for randomized and quasi-randomized studies of amnioreduction, laser coagulation and septostomy and compared their outcomes. We also searched conference proceedings and contacted the authors of published trials for clarification and additional data. No trials compared intervention with no intervention. Three studies (253 women) were included. Laser coagulation resulted in less overall death (48% vs. 59%; relative risk (RR), 0.81; 95% CI, 0.65-1.01 adjusted for clustering; two trials, 364 fetuses), perinatal death (26% vs. 44%; RR, 0.59; 95% CI, 0.40-0.87 adjusted for clustering; one trial, 284 fetuses) and neonatal death (8% vs. 26%; RR, 0.29; 95% CI, 0.14-0.61 adjusted for clustering; one trial, 284 fetuses) when compared with amnioreduction. There was no difference in perinatal outcome between amnioreduction and septostomy. More babies were alive without neurological abnormality at the age of 6 months in the laser group than in the amnioreduction group (52% vs. 31%; RR, 1.66; 95% CI, 1.17-2.35 adjusted for clustering; one trial). There was no difference in the proportion of babies alive at 6 months that had undergone treatment for major neurological abnormality between the laser coagulation and the amnioreduction groups (4% vs. 7%; RR, 0.58; 95% CI, 0.18-1.86 adjusted for clustering; one trial). The results suggest that endoscopic laser coagulation of anastomotic vessels should be considered in the treatment of all stages of TTTS to improve perinatal and neonatal outcome.

Interventions for the treatment of twin-twin transfusion syndrome.

BACKGROUND: Twin-twin transfusion syndrome, a condition affecting monochorionic twin pregnancies, is associated with a high risk of perinatal mortality and morbidity. A number of treatments have been introduced to treat the condition but it is unclear which intervention improves maternal and fetal outcome. OBJECTIVES: The objective of this review was to evaluate the impact of treatment modalities in twin-twin transfusion syndrome. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (October 2007) and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 4). We also searched conference proceedings and made personal contact with experts active in the area of the review. SELECTION CRITERIA: Randomised and quasi-randomised studies of amnioreduction versus laser coagulation, septostomy versus laser coagulation or septostomy versus amnioreduction. DATA COLLECTION AND ANALYSIS: One review author assessed eligibility and extracted data, which were checked by a second author. We contacted study authors for additional information. MAIN RESULTS: Two studies (213 women) were included. This review shows that laser coagulation of anastomotic vessels results in less death of both infants per pregnancy (relative risk (RR) 0.33; 95% confidence interval (CI) 0.16 to 0.67, one trial), less perinatal death (RR 0.59; 95% CI 0.0.40 to 0.87 adjusted for cluster, one trial) and less neonatal death (RR 0.29; 95% CI 0.14 to 0.61 adjusted for cluster, one trial) than in pregnancies treated with amnioreduction. There is no difference in perinatal outcome between amnioreduction and septostomy. A third study is awaiting assessment. More babies were alive without neurological abnormality at the age of six months in the laser group than the amnioreduction groups (RR 1.66; 95% CI 1.17 to 2.35 adjusted for clustering, one trial). This difference did not persist beyond six months of age. There was no significant difference in the babies alive at six months with neurological abnormality treated by laser coagulation or amnioreduction (RR 0.58; 95% CI 0.18 to 1.86 adjusted for clustering, one trial). AUTHORS' CONCLUSIONS: Endoscopic laser coagulation of anastomotic vessels should be considered in the treatment of all stages of twin-twin transfusion syndrome to improve perinatal outcome. Further research on the effect of treatment on milder forms of twin-twin transfusion syndrome (Quintero stage 1 and 2) are required. The long-term outcomes of survivors from the studies included in this review are required.

WITHDRAWN: Routine Doppler ultrasound in pregnancy.

BACKGROUND: Doppler ultrasound study of umbilical artery waveforms helps identify the compromised fetus in 'high risk' pregnancies and, therefore, deserves assessment as a screening test in 'low risk' pregnancies. One of the main aims of routine antenatal care is to identify the 'at risk' fetus in order to apply clinical interventions which could result in reduced perinatal morbidity and mortality. OBJECTIVES: To assess the effects on obstetric practice and pregnancy outcome of routine Doppler ultrasound in unselected and low risk pregnancies. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group Specialised Register of Controlled Trials and the Cochrane Controlled Trials Register were searched. Date of last search: September 1999 SELECTION CRITERIA: Acceptably controlled trials of routine Doppler ultrasound (umbilical circulation and/or uterine circulation) in unselected or low risk pregnancies. DATA COLLECTION AND ANALYSIS: Both reviewers assessed trial quality and extracted data. Authors of two trials were contacted for additional information. MAIN RESULTS: Five trials were included which recruited 14,338 women. The methodological quality of the trials was generally good. Based on existing evidence, routine Doppler ultrasound examination in low risk or unselected populations did not result in increased antenatal, obstetric and neonatal interventions, and no overall differences were detected for substantive short term clinical outcomes such as perinatal mortality. There is no available evidence to assess the effect on substantive long term outcomes such as childhood neurodevelopment. There is no available evidence to assess maternal outcomes, particularly psychological effects. In two studies there were unexpected findings suggesting possible harmful effects, but the explanation for this is not clear, and further evaluation regarding the safety of Doppler ultrasound is required. AUTHORS' CONCLUSIONS: Based on existing evidence, routine Doppler ultrasound in low risk or unselected populations does not confer benefit on mother or baby. Future research should be powerful enough to address small changes in perinatal outcome, and should include evaluation of maternal psychological effects, long term outcomes such as neurodevelopment, and issues of safety.

WITHDRAWN: Routine ultrasound in late pregnancy (after 24 weeks' gestation).

BACKGROUND: Diagnostic ultrasound is used selectively in late pregnancy where there are specific clinical indications. However, the value of routine late pregnancy ultrasound screening in unselected populations is controversial. The rationale for such screening would be the detection of clinical conditions which place the fetus or mother at high risk, which would not necessarily have been detected by other means such as clinical examination, and for which subsequent management would improve perinatal outcome. OBJECTIVES: To assess the effects on obstetric practice and pregnancy outcome of routine late pregnancy ultrasound, defined as greater than 24 weeks gestation, in women with either unselected or low risk pregnancies. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group Specialised Register of Controlled Trials and the Cochrane Controlled Trials Register were searched. SELECTION CRITERIA: All acceptably controlled trials of routine ultrasound in late pregnancy (defined as after 24 weeks). DATA COLLECTION AND ANALYSIS: The principal reviewer assessed trial quality and extracted data, under supervision of the co-reviewer. MAIN RESULTS: Seven trials recruiting 25,036 women were included. The quality of trials overall was satisfactory. There was no difference in antenatal, obstetric and neonatal intervention or morbidity in screened versus control groups. Routine late pregnancy ultrasound was not associated with improvements in overall perinatal mortality. Placental grading as an adjunct to third trimester examination scan was associated with a significant reduction in the stillbirth rate in the one trial that assessed it. There is a lack of data with regard to long term substantive outcomes such as neurodevelopment. There is a lack of data on maternal psychological effects. AUTHORS' CONCLUSIONS: Based on existing evidence, routine late pregnancy ultrasound in low risk or unselected populations does not confer benefit on mother or baby. There is a lack of data about the potential psychological effects of routine ultrasound in late pregnancy, and the effects on both short and long term neonatal and childhood outcome. Placental grading in the third trimester may be valuable, but whether reported results are reproducible remains to be seen, and future research of late pregnancy ultrasound should include evaluation of placental textural assessment.