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Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
The difference in the defect structures produced by different ion masses in a tungsten lattice is investigated using 80 MeV Au7+ ions and 10 MeV B3+ ions. The details of the defects produced by ions in recrystallized tungsten foil samples are studied using transmission electron microscopy. Dislocations of type b = 1/2 and  were observed in the analysis. While highly energetic gold ion produced small clusters of defects with very few dislocation lines, boron has produced large and sparse clusters with numerous dislocation lines. The difference in the defect structures could be due to the difference in separation between primary knock-on atoms produced by gold and boron ions.
To propose a new classification of inner-ear anomalies that is more clinically oriented and surgically relevant: the SMS (Sawai Man Singh) classification of cochleovestibular malformations.
A retrospective multicentric study was conducted of 436 cochlear implantations carried out in 3 Indian tertiary care institutes. Patients with anomalous anatomy were included and classified, as per the new SMS classification, into cochleovestibular malformation types I, II, III and IV, based on cochlear morphology, modiolus and lamina cribrosa.
There were 19, 23, 8 and 4 patients with cochleovestibular malformation types I, II, III and IV, respectively. Two-year post-operative Meaningful Auditory Integration Scale scores were statistically analysed.
This new classification for inner-ear anomalies is a simpler, more practical, outcome-oriented classification that can be used to better plan the surgery. These merits make it a more uniform classification for recording results.
Obstructive sleep apnoea is a common chronic sleep disorder characterised by collapse of the upper airway during sleep. The nasal airway forms a significant part of the upper airway and any obstruction is thought to have an impact on obstructive sleep apnoea. A systematic review was performed to determine the role of rhinological surgical interventions in the management of obstructive sleep apnoea.
A systematic review of current literature was undertaken; studies were included if they involved comparison of a non-surgical and/or non-rhinological surgical intervention with a rhinological surgical intervention for treatment of obstructive sleep apnoea.
Sixteen studies met the selection criteria. The pooled data suggest that there are reductions in the apnoea/hypopnea index and respiratory disturbance index following nasal surgery. However, the current body of studies is too heterogeneous for statistically significant meta-analysis to be conducted.
Nasal surgery may have limited benefit for a subset of patients based on current evidence.
Mental health and wellbeing, including addressing impacts of historical trauma and substance use among young people, has been identified as a key priority by Indigenous communities and leaders across Canada and globally. Yet, research to understand mental health among young Indigenous people who have used drugs is limited.
To examine longitudinal risk and strengths-based factors associated with psychological distress among young Indigenous people who use drugs.
The Cedar Project is an ongoing cohort study involving young Indigenous people who use drugs in Vancouver, Prince George, and Chase, British Columbia, Canada. This study included participants who completed the Symptom Checklist-90-Revised, returned for follow-up between 2010 and 2012, and completed the Childhood Trauma Questionnaire. Adjusted linear mixed-effects models estimated effects of study variables on changes in area T-scores of psychological distress.
Of 202 eligible participants, 53% were women and the mean age was 28 years. Among men, childhood maltreatment (emotional abuse, physical abuse, sexual abuse, physical neglect), any drug use, blackouts from drinking, and sex work were associated with increased distress. Among women, childhood maltreatment (emotional abuse, physical abuse, physical neglect), blackouts from drinking, and sexual assault were associated with increased distress, while having attempted to quit using drugs was associated with reduced distress. Marginal associations were observed between speaking their traditional language and living by traditional culture with lower distress among men.
Culturally safe mental wellness interventions are urgently needed to address childhood trauma and harmful coping strategies that exacerbate distress among young Indigenous people who use drugs.
Agriculture in the Central Himalayan Region depends on the availability of suitable germplasm as well as natural conditions. Due to extreme weather conditions, food and nutrition security is a major issue for communities inhabiting these remote and inaccessible areas. Millets are common crops grown in these areas. Foxtail millet (Setaria italica (L.) P. Beauv) is an important crop and forms a considerable part of the diet in this region. The aim of the present study was to explore, collect, conserve and evaluate the untapped genetic diversity of foxtail millet at the molecular level and discover variability in their nutritional traits. A total of 30 accessions having unique traits of agronomic importance were collected and molecular profiling was performed. A total of 63 alleles were generated with an average of 2.52 alleles per locus and average expected heterozygosity of 0.37 ± 0.231. Significant genetic variability was revealed through the genetic differentiation (Fst) and gene flow (Nm) values. Structure-based analysis divided whole germplasm into three sub-groups. Rich variability was found in nutritional traits such as dietary fibre in husked grains, carbohydrate, protein, lysine and thiamine content. The collected germplasm may be useful for developing nutritionally rich and agronomically beneficial varieties of foxtail millet and also designing strategies for utilization of unexploited genetic diversity for food and nutrition security in this and other similar agro-ecological regions.
The 98 min eclipsing cataclysmic variable EX Hya possesses a strong 67 min modulation in its light. This has led to a discussion of EX Hya in the context of intermediate polar variables. The observed P/Ṗ of the 67 min modulation provides a useful constraint on EX Hya models. Here we report additional timing data obtained over the interval 1982 to 1985 which bears on this matter.
Influenza A(H1N1) viruses of the 2009 pandemic (A(H1N1)pdm09) continue to cause outbreaks in the post-pandemic period. During January to May 2015, an upsurge of influenza was recorded that resulted in high fatality in central India. Genetic lineage, mutations in the hemagglutinin (HA) gene and infection by quasi-species are reported to affect disease severity. The objective of this study is to present the molecular and epidemiological trends during the 2015 influenza outbreak in central India. All the referred samples were subjected to qRT–PCR for diagnosis. HA gene sequencing (23 survivors and 24 non-survivors) and cloning were performed and analyzed using Molecular Evolutionary Genomic Analyzer (MEGA 5·05). Of the 3625 tested samples, 1607 (44·3%) were positive for influenza A(H1N1)pdm09, of which 228 (14·2%) individuals succumbed to death. A significant trend was observed in positivity (P = 0·003) and mortality (P < 0·0001) with increasing age. The circulating A(H1N1)pdm09 virus was characterized as belonging to clade-6B. Clinically significant mutations were detected. Patients infected with the quasi-species of the virus had a greater risk of death (P = 0·009). This study proposes a robust molecular and clinical surveillance program for the detection and characterization of the virus, along with prompt treatment protocols to prevent outbreaks.
The Global Muon Detector Network (GMDN) is composed by four ground cosmic ray detectors distributed around the Earth: Nagoya (Japan), Hobart (Australia), Sao Martinho da Serra (Brazil) and Kuwait city (Kuwait). The network has operated since March 2006. It has been upgraded a few times, increasing its detection area. Each detector is sensitive to muons produced by the interactions of ~50 GeV Galactic Cosmic Rays (GCR) with the Earth′s atmosphere. At these energies, GCR are known to be affected by interplanetary disturbances in the vicinity of the earth. Of special interest are the interplanetary counterparts of coronal mass ejections (ICMEs) and their driven shocks because they are known to be the main origins of geomagnetic storms. It has been observed that these ICMEs produce changes in the cosmic ray gradient, which can be measured by GMDN observations. In terms of applications for space weather, some attempts have been made to use GMDN for forecasting ICME arrival at the earth with lead times of the order of few hours. Scientific space weather studies benefit the most from the GMDN network. As an example, studies have been able to determine ICME orientation at the earth using cosmic ray gradient. Such determinations are of crucial importance for southward interplanetary magnetic field estimates, as well as ICME rotation.
In low- and middle-income countries, mental health training often includes sending few generalist clinicians to specialist-led programs for several weeks. Our objective is to develop and test a video-assisted training model addressing the shortcomings of traditional programs that affect scalability: failing to train all clinicians, disrupting clinical services, and depending on specialists.
We implemented the program -video lectures and on-site skills training- for all clinicians at a rural Nepali hospital. We used Wilcoxon signed-rank tests to evaluate pre- and post-test change in knowledge (diagnostic criteria, differential diagnosis, and appropriate treatment). We used a series of ‘Yes’ or ‘No’ questions to assess attitudes about mental illness, and utilized exact McNemar's test to analyze the proportions of participants who held a specific belief before and after the training. We assessed acceptability and feasibility through key informant interviews and structured feedback.
For each topic except depression, there was a statistically significant increase (Δ) in median scores on knowledge questionnaires: Acute Stress Reaction (Δ = 20, p = 0.03), Depression (Δ = 11, p = 0.12), Grief (Δ = 40, p < 0.01), Psychosis (Δ = 22, p = 0.01), and post-traumatic stress disorder (Δ = 20, p = 0.01). The training received high ratings; key informants shared examples and views about the training's positive impact and complementary nature of the program's components.
Video lectures and on-site skills training can address the limitations of a conventional training model while being acceptable, feasible, and impactful toward improving knowledge and attitudes of the participants.
To investigate the feasibility of a national audit of epistaxis management led and delivered by a multi-region trainee collaborative using a web-based interface to capture patient data.
Six trainee collaboratives across England nominated one site each and worked together to carry out this pilot. An encrypted data capture tool was adapted and installed within the infrastructure of a university secure server. Site-lead feedback was assessed through questionnaires.
Sixty-three patients with epistaxis were admitted over a two-week period. Site leads reported an average of 5 minutes to complete questionnaires and described the tool as easy to use. Data quality was high, with little missing data. Site-lead feedback showed high satisfaction ratings for the project (mean, 4.83 out of 5).
This pilot showed that trainee collaboratives can work together to deliver an audit using an encrypted data capture tool cost-effectively, whilst maintaining the highest levels of data quality.
Many medications administered to patients with schizophrenia possess anticholinergic properties. When aggregated, pharmacological treatments may result in a considerable anticholinergic burden. The extent to which anticholinergic burden has a deleterious effect on cognition and impairs ability to participate in and benefit from psychosocial treatments is unknown.
Seventy patients were followed for approximately 3 years. The MATRICS consensus cognitive battery (MCCB) was administered at baseline. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale. Ability to benefit from psychosocial programmes was measured using the DUNDRUM-3 Programme Completion Scale (D-3) at baseline and follow-up. Psychiatric symptoms were measured using the PANSS. Total antipsychotic dose was measured using chlorpromazine equivalents. Functioning was measured using the Social and Occupational Functioning Assessment Scale (SOFAS).
Mediation analysis found that the influence of anticholinergic burden on ability to participate and benefit from psychosocial programmes was completely mediated by the MCCB. For every 1-unit increase on the ACB scale, change scores for DUNDRUM-3 decreased by −0.27 points. This relationship appears specific to anticholinergic burden and not total antipsychotic dose. Moreover, mediation appears to be specific to cognition and not psychopathology. Baseline functioning also acted as mediator but only when MCCB was not controlled for.
Anticholinergic burden has a significant impact on patients’ ability to participate in and benefit from psychosocial treatment programmes. Physicians need to be mindful of the cumulative effect that medications can have on patient cognition, functional capacity and ability to benefit from psychosocial treatments.
Crimean-Congo haemorrhagic fever (CCHF) is an emerging zoonotic disease in India which is prevalent in neighbouring countries. CCHF virus (CCHFV) is a widespread tick-borne virus which is endemic in Africa, Asia, Eastern Europe and the Middle East. In the present study, samples of clinically suspected human cases from different areas of northern-western India were tested for the presence of CCHFV by RT–PCR through amplification of nucleocapsid (N) gene of CCHFV. Positive samples were sequenced to reveal the prevailing CCHFV genotype(s) and phylogenetic relatedness. A phylogenetic tree revealed the emergence of diverse strains in the study region showing maximum identity with the Pakistan, Afghanistan and Iran strains, which was different from earlier reported Indian strains. Our findings reveal for the first time the emergence of the Asia 1 group in India; while earlier reported CCHFV strains belong to the Asia 2 group.
We have measured 14C, 210Pb and 137Cs profiles in two representative cores from Manasbal Lake, Kashmir, India. The sedimentation rate derived from 210Pb and 137Cs in the upper part of the core is in the range of 3.4 to 5.5 mm yr−1. In contrast, 14C ages show an inversion at depths >20 cm. These results are attributed to the erosion of the ubiquitous 10–20-m-thick loess mantle, based on the similarity of 14C ages of the inversion layer in the sediments and the paleosols present in the catchment area. Frequency-dependent mineral magnetic susceptibility (χfd), carbon to nitrogen ratios and pigment concentrations in the profile show a significant amount of allochthonous component in the lake deposits and support the conclusion that the 14C dates do not reflect the chronology of the in-situ lake sedimentation but episodic deposition of the surrounding loess. Thus, 14C serves as a useful tracer to understand source components of the sediments.
Sedimentological, mineral magnetic and carbon isotopic studies on cores from Mansar Lake in the Jammu area provide paleomonsoonal history dating back to 580 bc. From ca. 580 bc to ad 300, the region experienced precipitation similar to the present, whereas from ad 300 to 1400, the monsoon was relatively subdued. A small excursion ca. ad 1100 suggests an effect of medieval warming. Studies in the Kumaon region did not provide a proper precipitation record, as anthropogenic activity interfered with sedimentation. Manasbal Lake in Kashmir gave an inversion of 14C chronology due to younger paleosols in the drainage basin. Further, the episodic nature of sedimentation in Manasbal Lake hampered the reconstruction of precipitation history in the area.
Heat stress greatly limits the productivity of wheat in many regions. Knowledge on the degree of genetic diversity of wheat varieties along with their selective traits will facilitate the development of high yielding, stress-tolerant wheat cultivar. The objective of this study were to determine genetic variation in morpho-physiological traits associated with heat tolerance in 30 diverse wheat genotypes and to examine genetic diversity and relationship among the genotypes varying heat tolerance using molecular markers. Phenotypic data of 15 traits were evaluated for heat tolerance under non-stress and stress conditions for two consecutive years. A positive and significant correlation among cell membrane stability, canopy temperature depression, biomass, susceptibility index and grain yield was shown. Genetic diversity assessed by 41 polymorphic simple sequence repeat (SSR) markers was compared with diversity evaluated for 15 phenotypic traits averaged over stress and non-stress field conditions. The mean polymorphic information content for SSR value was 0.38 with range of 0.12–0.75. Based on morpho-physiological traits and genotypic data, three groups were obtained based on their tolerance (HHT, MHT and LHT) levels. Analysis of molecular variance explained 91.7% of the total variation could be due to variance within the heat tolerance genotypes. Genetic diversity among HHT was higher than LHT genotypes and HHT genotypes were distributed among all cluster implied that genetic basis of heat tolerance in these genotypes was different thereby enabling the wheat breeders to combine these diverse sources of genetic variation to improve heat tolerance in wheat breeding programme.
Rotavirus (RV) infection causes acute infantile diarrhoea in humans and animals and remains a major concern for vaccine development. The close proximity of humans to animals may foster cross-species infection resulting in the emergence of novel/unusual strains by genetic reassortment. In this study, we characterized 500 diarrhoeal samples for group A rotaviruses (RVA) from children (n = 290), piglets (n = 95) and calves (n = 115) in Northeast India during 2012–2013. The data showed that 142/500 (28·4%) faecal samples were positive for RVA with the highest level of infection detected in piglets (57/142, 40·1%) followed by children (51/142, 35·9%) and calves (34/142, 23·9%). Sequence-based G- and P-typing showed G1P (25%) and G1P (35%) were the prevailing genotypes in both humans and animals. Single cases of unusual genotypes, i.e. G9P, G5P in humans and G1P, G1P and G3P in animals were also identified. Cluster analyses of the sequences showed regional strains were genetically closer to their homologous strains. However, human G5P and porcine G1P strains showed homology to heterologous hosts of their prototype strains. The subsequent global spread of unusual RV strains may result in their establishment over time, presenting challenges to future vaccine evaluation programmes. More studies on emerging genotypes are required to elucidate how RVA strains evolve post-vaccination. This study supports the need for continuous surveillance of RVA infections after detecting from diverse hosts in a common setting.
The binary X-ray source GX 1 + 4 was observed during a balloon flight in 1986, November. The source was in a relatively high intensity state. Time analysis of the data shows that the pulsation period was 111.8 ± 1.0 s indicating that one or more episodes of spin-down occurred between 1980 and 1986. Folded pulse profiles are very broad with an indication of a notch at the peak. Evidence has been found for a correlation between hard X-ray intensity and phase of the proposed 304 day orbital period. The time averaged intensity since 1980 is an order of magnitude lower than during the 1970’s. A survey of the post 1980 data shows that several reversals of the period derivative have occurred. Spin-up at the rates typical of the 1970’s has been followed by a dramatic spin-down episode with dP/dt>2.4 × 10−7 s/s.
In search of a suitable resource conservation technology under pigeonpea (Cajanus cajan L.)–wheat (Triticum aestivum L.) system in the Indo-Gangetic Plains, the effects of conservation agriculture (CA) on crop productivity and water-use efficiency (WUE) were evaluated during a 3-year study. The treatments were: conventional tillage (CT), zero tillage (ZT) with planting on permanent narrow beds (PNB), PNB with residue (PNB + R), ZT with planting on permanent broad beds (PBB) and PBB + R. The PBB + R plots had higher pigeonpea grain yield than the CT plots in all 3 years. However, wheat grain yields under all plots were similar in all years except for PBB + R plots in the second year, which had higher wheat yield than CT plots. The contrast analysis showed that pigeonpea grain yield of CA plots was significantly higher than CT plots in the first year. However, both pigeonpea and wheat grain yields during the last 2 years under CA and CT plots were similar. The PBB + R plots had higher system WUE than the CT plots in the second and third years. Plots under CA had significantly higher WUE and significantly lower water use than CT plots in these years. The PBB + R plots had higher WUE than PNB + R and PNB plots. Also, the PBB plots had higher WUE than PNB in the second and third years, despite similar water use. The interactions of bed width and residue management for all parameters in the second and third years were not significant. Those positive impacts under PBB + R plots over CT plots were perceived to be due to no tillage and significantly higher amount of estimated residue retention. Thus, both PBB and PBB + R technologies would be very useful under a pigeonpea–wheat cropping system in this region.