Protein signaling and morphological development of the tail fluke in the embryonic beluga whale (Delphinapterus leucas).

BACKGROUND: During the land-to-sea transition of cetaceans (whales, dolphins, and porpoises), the hindlimbs were lost and replaced by an elaborate tail fluke that evolved 32 Ma. All modern cetaceans utilize flukes for lift-based propulsion, and nothing is known of this organ's molecular origins during embryonic development. This study utilizes immunohistochemistry to identify the spatiotemporal location of protein signals known to drive appendage outgrowth in other vertebrates (e.g., Sonic Hedgehog [SHH], GREMLIN [GREM], wingless-type family member 7a [WNT], and fibroblast growth factors [FGFs]) and to test the hypothesis that signals associated with outgrowth and patterning of the tail fluke are similar to a tetrapod limb. Specifically, this study utilizes an embryo of a beluga whale (Delphinapterus leucas) as a case study. RESULTS: Results showed epidermal signals of WNT and FGFs, and mesenchymal/epidermal signals of SHH and GREM. These patterns are most consistent with vertebrate limb development. Overall, these data are most consistent with the hypothesis that outgrowth of tail flukes in cetaceans employs a signaling pattern that suggests genes essential for limb outgrowth and patterning shape this evolutionarily novel appendage. CONCLUSIONS: While these data add insights into the molecular signals potentially driving the evolution and development of tail flukes in cetaceans, further exploration of the molecular drivers of fluke development is required.

Reducing implicit bias in the neurosurgery application and interview process: a single-institution experience.

OBJECTIVE: The neurosurgical match is a challenging process for applicants and programs alike. Programs must narrow a wide field of applicants to interview and then determine how to rank them after limited interaction. To streamline this, programs commonly screen applicants using United States Medical Licensing Examination (USMLE) Step scores. However, this approach removes nuance from a consequential decision and exacerbates existing biases. The primary objective of this study was to demonstrate the feasibility of effecting minor modifications to the residency application process, as the authors have done at their institution, specifically by reducing the prominence of USMLE board scores and Alpha Omega Alpha (AΩA) status, both of which have been identified as bearing racial biases. METHODS: At the authors' institution, residents and attendings holistically reviewed applications with intentional redundancy so that every file was reviewed by two individuals. Reviewers were blinded to applicants' photographs and test scores. On interview day, the applicant was evaluated for their strength in three domains: knowledge, commitment to neurosurgery, and integrity. For rank discussions, applicants were reviewed in the order of their domain scores, and USMLE scores were unblinded. A regression analysis of the authors' rank list was made by regressing the rank list by AΩA status, Step 1 score, Step 2 score, subinternship, and total interview score. RESULTS: No variables had a significant effect on the rank list except total interview score, for which a single-point increase corresponded to a 15-position increase in rank list when holding all other variables constant (p < 0.05). CONCLUSIONS: The goal of this holistic review and domain-based interview process is to mitigate bias by shifting the focus to selected core qualities in lieu of traditional metrics. Since implementation, the authors' final rank lists have closely reflected the total interview score but were not significantly affected by board scores or AΩA status. This system allows for the removal of known sources of bias early in the process, with the aim of reducing potential downstream effects and ultimately promoting a final list that is more reflective of stated values.

Turnover Time Between Elective Operative Cases: Does the Witching Hour Exist for the Operating Room?

BACKGROUND: Efficient resource management in the operating room (OR) contributes significantly to healthcare expenditure and revenue generation for health systems. We aim to assess the influence that surgeon, anesthesiology, and nursing team assignments and time of day have on turnover time (TOT) in the OR. METHODS: We performed a retrospective review of elective cases at a single academic hospital that were completed between Monday and Friday between the hours of 0700 and 2359 from July 1, 2017, through March 31, 2018. Emergent cases and unplanned, add-on cases were excluded. Data regarding patient characteristics, OR teams, TOT, and procedure start and end times were collected and analyzed. RESULTS: A total of 2174 total cases across 13 different specialties were included in our study. A multivariate regression of relevant variables affecting TOT was performed. Consecutive specialty (p < 0.0001), consecutive surgeon (p < 0.0001), anesthesiologist (p < 0.0001), and prior case ending before 1400 (p < 0.0001) were independent predictors of lower TOT. A receiver operating characteristic analysis demonstrated an area under the curve of 0.848 and a cutoff of 1400 having the highest sensitivity and specificity for TOT difference. CONCLUSIONS: TOT can be significantly affected by the time of the day the procedure is performed. Staffing availability during late procedures and the differences in how OR team staff are scheduled may affect OR efficiency. Additional studies may be needed to determine the long-term implications of changes implemented to decrease organizational operational costs related to the OR.

Triple-negative breast cancers with expression of glucocorticoid receptor in immune cells show better prognosis.

Background: Glucocorticoid receptor (GR) is shown to have variable frequency of expression in invasive tumors of the breast. Investigation of additional nuclear receptors like GR in receptor negative tumors like triple negative breast cancer (TNBC) may have prognostic and therapeutic significance. Methods: Expression of GR was evaluated by immunohistochemistry in 175 tumors of invasive breast cancer with long term follow up. GR Expression was separately evaluated in invasive tumor cells, stromal cells and tumor infiltrating lymphocytes (TIL's). Staining pattern was categorised as positive when more than 1% of the cells stained in each subpopulation of cells. Disease free survival was analysed between GR positive and negative status by Kaplan Meier analysis. Results: Of the 175 tumors, 121 (70%) were ER positive, 53 (30%) were ER negative and 29% (51) were triple negative. 74% (130/175) tumors showed expression of GR in invasive tumor cells while (84%) 147/175 had expression in TIL's. No significant difference in distribution of GR was noted between ER positive and ER negative tumors (78% vs 66%, p-0.1). Of the TNBC's 54% (28/51) and 70% (36/51) showed expression of GR in invasive tumor and TIL's respectively. Overall, GR positive tumors had significant better survival than GR negative tumors (mean survival time of 85 vs 59 months respectively, p-0.04) Contrary to the reports that GR expression in TIL's are associated with immunosuppressive activity in model systems, TNBC's with increased expression of GR in immune cells were associated with better survival (Mean survival time 74 vs 41 months, log rank test- p-0.03). TNBC tumors which were GR negative had higher lymph node metastases (p-0.04) and none of the other clinical features like age, menopausal state, tumor size and grade were different between GR positive and negative tumors within TNBC. Conclusions: Glucocorticoids (GC) are often used to alleviate the adverse symptoms during chemotherapy. Determining the GR status is of importance due to the pro cell survival effect of the glucocorticoids mediated through GR during chemotherapy. Though GC mediated effects on chemotherapy are controversial, our results indicate favourable effects in TNBC.

Perinatal mental health in India: protocol for a validation and cohort study.

BACKGROUND: Common mental disorders (CMD) are among the largest contributors to global maternal morbidity and mortality. Although research on perinatal mental health in India has grown in recent years, important evidence gaps remain, especially regarding CMD. Our study aims to improve understanding of CMD among perinatal and non-perinatal women of reproductive age across two settings in India: Bangalore (Karnataka) and Tanda (Himachal Pradesh). METHODS: The study is embedded within the Maternal and Perinatal Health Research Collaboration India (MaatHRI). This mixed-methods observational study comprises three consecutive phases: (i) focus group discussions and individual interviews to explore women's knowledge and seek feedback on CMD screening tools; (ii) validation of CMD screening tools; and (iii) prospective cohort study to identify CMD incidence, prevalence and risk factors among perinatal and non-perinatal women. Results of the three phases will be analyzed using inductive thematic analysis, psychometric analysis and multivariable regression analysis, respectively. CONCLUSION: Improving understanding, detection and management of CMD among women is key to improving women's health and promoting gender equality. This study will provide evidence of CMD screening tools for perinatal and non-perinatal women in two diverse Indian settings, produce data on CMD prevalence, incidence and risk factors and enhance understanding of the specific contribution of the perinatal state to CMD.

Goat as the ideal climate-resilient animal model in tropical environment: revisiting advantages over other livestock species.

In the agriculture sector, livestock are considered extremely resilient to climate change and are tipped to play a significant role in ensuring food security to meet the increased demands of growing human population by 2050. Compared to other domestic species, goats are considered the ideal animal model for climate change due to its high thermal and drought resilience, ability to survive on limited pastures, and high disease resistance. This review is therefore a revisit to the advantages of rearing goats over other livestock species under current and future trends of changes in climate, particularly to cope with recurrent multiple stressors such as heat load, and lack of water and feed. In summary, goats, also called as poor man's cow, are preferred by the small-scale landless farmers due to their low input and assured higher output system, as they require low initial investment, with minimum specialized facilities and labors. Furthermore, they perceive goats as better resilient animal to cope with multiple stressors such as heat load, and water and feed scarcity, and possess better skills to cope with bush, when compared with sheep and cattle. The unique capacity for employing behavioral plasticity and morphological features of goats gives them clear advantage over sheep and cattle, when coping with seasonal biotopes, and experiences of water and feed shortage. When facing with low-quality feed, they also are superior to cattle and sheep to digest dry matter and to recycle nitrogen. Additionally, goats have superior ability to desiccate feces and concentrate urine, when compared with sheep and cattle. These advantages make goat the go-to species for efficiently countering the adversities associated with climate change and to optimize appropriate economic return through sustained production. Therefore, goats are tipped to be the future animals with extreme potential to counter the projected alarming climate change impacts and expected to play a significant role in ensuring food security to meet the demands of the growing human population by the end of this century.

Growth, morphology and electronic properties of epitaxial graphene on vicinal Ir(332) surface.

Superlattice induced minigaps in graphene band structure due to underlying one-dimensional nanostructuration has been demonstrated. A superperiodic potential can be introduced in graphene if the substrate is periodically structured. The successful preparation of a periodically nanostructured substrate in large scale can be obtained by carefully studying the electronic structure with a spatial averaging technique such as high-energy resolution photoemission. In this work, we present two different growth methods such as temperature programmed growth (TPG) and chemical vapor deposition (CVD) studied by scanning tunnelling microscopy (STM) and low energy electron diffraction (LEED). In both methods, we show that the original steps of Ir(332) have modified with (111) terraces and step bunching after graphene growth. Graphene grows continuously over the terrace and the step bunching areas. We observe that while TPG growth does not give rise to a well-defined surface periodicity required for opening a bandgap, the CVD growth does. By combining with angle-resolved photoemission spectroscopy (ARPES) measurements, we correlate the obtained spatial periodicity to observed band gap opening in graphene.

Extended memory lifetime in spiking neural networks employing memristive synapses with nonlinear conductance dynamics.

Spiking neural networks (SNNs) employing memristive synapses are capable of life-long online learning. Because of their ability to process and classify large amounts of data in real-time using compact and low-power electronic systems, they promise a substantial technology breakthrough. However, the critical issue that memristor-based SNNs have to face is the fundamental limitation in their memory capacity due to finite resolution of the synaptic elements, which leads to the replacement of old memories with new ones and to a finite memory lifetime. In this study we demonstrate that the nonlinear conductance dynamics of memristive devices can be exploited to improve the memory lifetime of a network. The network is simulated on the basis of a spiking neuron model of mixed-signal digital-analogue sub-threshold neuromorphic CMOS circuits, and on memristive synapse models derived from the experimental nonlinear conductance dynamics of resistive memory devices when stimulated by trains of identical pulses. The network learning circuits implement a spike-based plasticity rule compatible with both spike-timing and rate-based learning rules. In order to get an insight on the memory lifetime of the network, we analyse the learning dynamics in the context of a classical benchmark of neural network learning, that is hand-written digit classification. In the proposed architecture, the memory lifetime and the performance of the network are improved for memristive synapses with nonlinear dynamics with respect to linear synapses with similar resolution. These results demonstrate the importance of following holistic approaches that combine the study of theoretical learning models with the development of neuromorphic CMOS SNNs with memristive devices used to implement life-long on-chip learning.

Neurodevelopmental disorders in children aged 2-9 years: Population-based burden estimates across five regions in India.

BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.

Toxic hazards of ammonia release and population vulnerability assessment using geographical information system.

Today, chemical industries manufacture, store and transport evermore hazardous substances and hence the risk of accidental releases of these chemicals can become more and more catastrophic in the context of increasing population and their requirements. The damage potential is proportional to the population characteristics of the location as well as various meteorological factors and geographical features. For the risk assessment of ammonia toxicity, the storage facility at Eloor industrial area is taken as a sample. Pollutant dispersion model - Areal Locations of Hazardous Atmosphere (ALOHA) is utilized to predict the toxicity impacted distance of ammonia. The model estimates the vulnerable areas, which may be affected toxically by an Ammonia release by integrating information about chemical properties of the substance, weather conditions prevalent in the area and release conditions. Risk assessment is done for four different atmospheric conditions, typical to the prevailing seasons and affected area is estimated in each scenario. To determine the affected population, the areal interpolation method in GIS database is also employed in this study, which illustrates the toxically impacted areas and the population in need of immediate help and evacuation. Such studies can serve as an effective tool for decision makers to prepare an emergency plan in case of accidental releases.

Current application of CRISPR/Cas9 gene-editing technique to eradication of HIV/AIDS.

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) remains a major health hazard despite significant advances in prevention and treatment of HIV infection. The major reason for the persistence of HIV/AIDS is the inability of existing treatments to clear or eradicate the multiple HIV reservoirs that exist in the human body. To suppress the virus replication and rebound, HIV/AIDS patients must take life-long antiviral medications. The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system is an emerging gene-editing technique with the potential to eliminate or disrupt HIV-integrated genomes or HIV-infected cells from multiple HIV reservoirs, which could result in the complete cure of HIV/AIDS. Encouraging progress has already been reported for the application of the CRISPR/Cas9 technique to HIV/AIDS treatment and prevention, both in vitro in human patient cells and in vivo in animal model experiments. In this review, we will summarize the most recent progress in the application of the CRISPR/Cas9 gene-editing technique to HIV/AIDS therapy and elimination. Future directions and trends of such applications are also discussed.

Antivirulence Properties of Probiotics in Combating Microbial Pathogenesis.

Probiotics are nonpathogenic microorganisms that confer a health benefit on the host when administered in adequate amounts. Ample evidence is documented to support the potential application of probiotics for the prevention and treatment of infections. Health benefits of probiotics include prevention of diarrhea, including antibiotic-associated diarrhea and traveler's diarrhea, atopic eczema, dental carries, colorectal cancers, and treatment of inflammatory bowel disease. The cumulative body of scientific evidence that demonstrates the beneficial effects of probiotics on health and disease prevention has made probiotics increasingly important as a part of human nutrition and led to a surge in the demand for probiotics in clinical applications and as functional foods. The ability of probiotics to promote health is attributed to the various beneficial effects exerted by these microorganisms on the host. These include lactose metabolism and food digestion, production of antimicrobial peptides and control of enteric infections, anticarcinogenic properties, immunologic enhancement, enhancement of short-chain fatty acid production, antiatherogenic and cholesterol-lowering attributes, regulatory role in allergy, protection against vaginal or urinary tract infections, increased nutritional value, maintenance of epithelial integrity and barrier, stimulation of repair mechanism in cells, and maintenance and reestablishment of well-balanced indigenous intestinal and respiratory microbial communities. Most of these attributes primarily focus on the effect of probiotic supplementation on the host. Hence, in most cases, it can be concluded that the ability of a probiotic to protect the host from infection is an indirect result of promoting overall health and well-being. However, probiotics also exert a direct effect on invading microorganisms. The direct modes of action resulting in the elimination of pathogens include inhibition of pathogen replication by producing antimicrobial substances like bacteriocins, competition for limiting resources in the host, antitoxin effect, inhibition of virulence, antiadhesive and antiinvasive effects, and competitive exclusion by competition for binding sites or stimulation of epithelial barrier function. Although much has been documented about the ability of probiotics to promote host health, there is limited discussion on the above mentioned effects of probiotics on pathogens. Being in an era of antibiotic resistance, a better understanding of this complex probiotic-pathogen interaction is critical for development of effective strategies to control infections. Therefore, this chapter will focus on the ability of probiotics to directly modulate the infectious nature of pathogens and the underlying mechanisms that mediate these effects.

Factors associated with maternal mortality at advanced maternal age: a population-based case-control study.

OBJECTIVE: This study aimed to examine the factors associated with maternal mortality among women aged ≥35 years. DESIGN: Unmatched population based case-control study. SETTING: United Kingdom. POPULATION: Between 2009 and 2012, 105 cases of maternal deaths aged ≥35 years were extracted from the surveillance database of the MBRRACE-UK confidential enquiries into maternal deaths in the UK. In addition, 766 controls aged ≥35 years were identified from the UK Obstetric Surveillance System (2005-2012). METHODS: Risk factors known to be associated with maternal mortality and morbidity and for which data were available were examined for their association with maternal mortality among women ≥35 years using logistic regression analysis. MAIN OUTCOME MEASURES: Odds ratios and 95% confidence intervals associated with maternal death. RESULTS: Five factors were found to be significantly associated with increased odds of death among women aged ≥35 years: smoking during pregnancy (adjusted odds ratio (aOR) 2.06, 95% CI 1.13-3.75), inadequate use of antenatal care (aOR 23.62, 95% CI 8.79-63.45), medical co-morbidities (aOR 5.92, 95% CI 3.56-9.86) and previous pregnancy problems (aOR 2.06, 95% CI 1.23-3.45). The odds associated with death increased by 12% per year increase in age (aOR 1.12, 95% CI 1.02-1.22). CONCLUSION: Age was associated with maternal mortality even after adjusting for other known risk factors. Importantly, this study showed an association between maternal mortality and smoking among women aged 35 years or older. It emphasises the importance of public health action to reduce smoking levels and address trends in rising maternal age. TWEETABLE ABSTRACT: Smoking is a risk factor for maternal death for those aged over 35 years.

Research priorities in Maternal, Newborn, & Child Health & Nutrition for India: An Indian Council of Medical Research-INCLEN Initiative.

In India, research prioritization in Maternal, Newborn, and Child Health and Nutrition (MNCHN) themes has traditionally involved only a handful of experts mostly from major cities. The Indian Council of Medical Research (ICMR)-INCLEN collaboration undertook a nationwide exercise engaging faculty from 256 institutions to identify top research priorities in the MNCHN themes for 2016-2025. The Child Health and Nutrition Research Initiative method of priority setting was adapted. The context of the exercise was defined by a National Steering Group (NSG) and guided by four Thematic Research Subcommittees. Research ideas were pooled from 498 experts located in different parts of India, iteratively consolidated into research options, scored by 893 experts against five pre-defined criteria (answerability, relevance, equity, investment and innovation) and weighed by a larger reference group. Ranked lists of priorities were generated for each of the four themes at national and three subnational (regional) levels [Empowered Action Group & North-Eastern States, Southern and Western States, & Northern States (including West Bengal)]. Research priorities differed between regions and from overall national priorities. Delivery domain of research which included implementation research constituted about 70 per cent of the top ten research options under all four themes. The results were endorsed in the NSG meeting. There was unanimity that the research priorities should be considered by different governmental and non-governmental agencies for investment with prioritization on implementation research and issues cutting across themes.

Microglia-derived HIV Nef+ exosome impairment of the blood-brain barrier is treatable by nanomedicine-based delivery of Nef peptides.

The negative factor (Nef) of human immunodeficiency virus (HIV) is an accessory protein that is thought to be integral to HIV-associated immune- and neuroimmune pathogenesis. Here, we show that nef-transfected microglia-released Nef+ exosome (exNef) disrupts the apical blood-brain barrier (BBB) and that only nef-transfected microglia release Nef in exosomes. nef-gfp-transduced neurons and astrocytes release exosomes but did not release exNef in the extracellular space. Apical administration of exNef derived from nef-transfected 293T cells reduced transendothelial electrical resistance (TEER) and increased permeability of the BBB. Microglia-derived exNef applied to either the apical/basal BBB significantly reduced expression of the tight junction protein, ZO-1, suggesting a mechanism of exNef-mediated neuropathogenesis. Microglia exposed to exNef release elevated levels of Toll-like receptor-induced cytokines and chemokines IL-12, IL-8, IL-6, RANTES, and IL-17A. Magnetic nanoparticle delivery of Nef peptides containing the Nef myrisolation site across an in vitro BBB ultimately reduced nef-transfected microglia release of Nef exosomes and prevented the loss of BBB integrity and permeability as measured by TEER and dextran-FITC transport studies, respectively. Overall, we show that exNef is released from nef-gfp-transfected microglia; exNef disrupts integrity and permeability, and tight junctions of the BBB, and induces microglial cytokine/chemokine secretion. These exNef-mediated effects were significantly restricted by Nef peptides. Taken together, this study provides preliminary evidence of the role of exNef in HIV neuroimmune pathogenesis and the feasibility of a nanomedicine-based therapeutics targeting exNef to treat HIV-associated neuropathogenesis.

Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II.

Mucopolysaccharidoses (MPS), a subgroup of lysosomal storage disorders, are caused due to deficiency of specific lysosomal enzyme involved in catabolism of glycosaminoglycans. To date more than 200 pathogenic variants in the alpha-l-iduronidase (IDUA) for MPS I and ∼500 pathogenic variants in the iduronate-2-sulphatase (IDS) for MPS II have been reported worldwide. The mutation spectrum of MPS type I and MPS type II disorders in Indian population is not characterized yet. In this study, we carried out clinical, biochemical, molecular and in silico analyses to establish the mutation spectrum of MPS I and MPS II in the Indian population. We conducted molecular analysis for 60 MPS-affected patients [MPS I (n = 30) (Hurler syndrome = 17, Hurler-Scheie syndrome = 13), and MPS II (n = 30) (severe = 18, attenuated = 12)] and identified a total of 44 [MPS I (n = 22) and MPS II (n = 22)] different pathogenic variants comprising missense, nonsense, frameshift, gross deletions and splice site variants. A total of 20 [MPS I (n = 14), and MPS II (n = 6)] novel pathogenic sequence variants were identified in our patient cohort. We found that 32% of pathogenic variants detected in IDUA were recurrent and 25% in MPS II. This is the first study revealing the mutation spectrum of MPS I and MPS II patients in the Indian population.

Risk factors and newborn outcomes associated with maternal deaths in the UK from 2009 to 2013: a national case-control study.

OBJECTIVES: To identify the risk factors for and adverse newborn outcomes associated with maternal deaths from direct and indirect causes in the UK. DESIGN: Unmatched case-control analysis. SETTING: All hospitals caring for pregnant women in the UK. POPULATION: Comprised 383 women who died (cases) from direct or indirect causes from 2009 to 2013 (Confidential Enquiry into Maternal Deaths in the UK) and 1516 women who did not have any life-threatening complications during pregnancy and childbirth (controls) obtained from UK Obstetric Surveillance System (UKOSS). METHODS: Multivariable regression analyses were undertaken to examine potential risk factors, their incremental effects, and adverse newborn outcomes associated with maternal deaths. OUTCOMES: Odds ratios associated for risk factors for maternal death and newborn outcomes (stillbirth, admission to neonatal intensive care unit [NICU], early neonatal death) and incremental risk. RESULTS: Seven factors, of 13 examined, were independently associated with increased odds of maternal death: pre-existing medical comorbidities (adjusted odds ratio [aOR] 8.65; 95% CI 6.29-11.90), anaemia during pregnancy (aOR 3.58; 95% CI 1.14-11.21), previous pregnancy problems (aOR 1.85; 95% CI 1.33-2.57), inadequate use of antenatal care (aOR 46.85; 95% CI 19.61-111.94), substance misuse (aOR 12.21; 95% CI 2.33-63.98), unemployment (aOR 1.81; 95% CI 1.08-3.04) and maternal age (aOR 1.06; 95% CI 1.04-1.09). There was a four-fold increase in the odds of death per unit increase in the number of risk factors. Odds of stillbirth, admission to NICU and early neonatal death were higher among women who died. CONCLUSION: This study reiterates the need for optimal care for women with medical comorbidities and older age, and the importance of adequate antenatal care. It demonstrates the existence of socio-economic inequalities in maternal death in the UK. TWEETABLE ABSTRACT: Medical comorbidities and socio-economic inequalities are important risk factors for maternal death in the UK.

Semiconducting Graphene from Highly Ordered Substrate Interactions.

While numerous methods have been proposed to produce semiconducting graphene, a significant band gap has never been demonstrated. The reason is that, regardless of the theoretical gap formation mechanism, subnanometer disorder prevents the required symmetry breaking necessary to make graphene semiconducting. In this work, we show for the first time that semiconducting graphene can be made by epitaxial growth. Using improved growth methods, we show by direct band measurements that a band gap greater than 0.5 eV can be produced in the first graphene layer grown on the SiC(0001) surface. This work demonstrates that order, a property that remains lacking in other graphene systems, is key to producing electronically viable semiconducting graphene.

Progression from severe sepsis in pregnancy to death: a UK population-based case-control analysis.

OBJECTIVE: To identify factors associated with progression from pregnancy-associated severe sepsis to death in the UK. DESIGN: A population-based case-control analysis using data from the UK Obstetric Surveillance System (UKOSS) and the UK Confidential Enquiry into Maternal Death (CEMD). SETTING: All pregnancy care and death settings in UK hospitals. POPULATION: All non-influenza sepsis-related maternal deaths (January 2009 to December 2012) were included as cases (n = 43), and all women who survived severe non-influenza sepsis in pregnancy (June 2011 to May 2012) were included as controls (n = 358). METHODS: Cases and controls were identified using the CEMD and UKOSS. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals. MAIN OUTCOME MEASURES: Odds ratios for socio-demographic, medical, obstetric and management factors in women who died from sepsis, compared with those who survived. RESULTS: Four factors were included in the final regression model. Women who died were more likely to have never received antibiotics [aOR = 22.7, 95% confidence interval (CI) 3.64-141.6], to have medical comorbidities (aOR = 2.53, 95%CI 1.23-5.23) and to be multiparous (aOR = 3.57, 95%CI 1.62-7.89). Anaemia (aOR = 13.5, 95%CI 3.17-57.6) and immunosuppression (aOR = 15.0, 95%CI 1.93-116.9) were the two most important factors driving the association between medical comorbidities and progression to death. CONCLUSIONS: There must be continued vigilance for the risks of infection in pregnant women with medical comorbidities. Improved adherence to national guidelines, alongside prompt recognition and treatment with antibiotics, may reduce the burden from sepsis-related maternal deaths. TWEETABLE ABSTRACT: Medical comorbidities, multiparity and antibiotic delays increase the risk of death from maternal sepsis.

Factors associated with maternal death from direct pregnancy complications: a UK national case-control study.

OBJECTIVE: To investigate the factors associated with maternal death from direct pregnancy complications in the UK. DESIGN: Unmatched case-control analysis. SETTING: All hospitals caring for pregnant women in the UK. POPULATION: A total of 135 women who died (cases) between 2009 and 2012 from eclampsia, pulmonary embolism, severe sepsis, amniotic fluid embolism, and peripartum haemorrhage, using data from the Confidential Enquiry into Maternal Death, and another 1661 women who survived severe complications (controls) caused by these conditions (2005-2013), using data from the UK Obstetric Surveillance System. METHODS: Multivariable regression analyses were undertaken to identify the factors that were associated with maternal deaths and to estimate the additive odds associated with the presence of one or more of these factors. MAIN OUTCOME MEASURES: Odds ratios associated with maternal death and population-attributable fractions, with 95% confidence intervals. Incremental risk of death associated with the factors using a 'risk factors' score. RESULTS: Six factors were independently associated with maternal death: inadequate use of antenatal care (adjusted odds ratio, aOR 15.87, 95% CI 6.73-37.41); substance misuse (aOR 10.16, 95% CI 1.81-57.04); medical comorbidities (aOR 4.82, 95% CI 3.14-7.40); previous pregnancy problems (aOR 2.21, 95% CI 1.34-3.62); hypertensive disorders of pregnancy (aOR 2.44, 95% CI 1.31-4.52); and Indian ethnicity (aOR 2.70, 95% CI 1.14-6.43). Of the increased risk associated with maternal death, 70% (95% CI 66-73%) could be attributed to these factors. Odds associated with maternal death increased by three and a half times per unit increase in the 'risk factor' score (aOR 3.59, 95% CI 2.83-4.56). CONCLUSIONS: This study shows that medical comorbidities are importantly associated with direct (obstetric) deaths. Further studies are required to understand whether specific aspects of care could be improved to reduce maternal deaths among women with medical comorbidities in the UK.