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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.
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 red panda Ailurus fulgens is categorized as Endangered on the IUCN Red List and is threatened by anthropogenic pressures such as livestock grazing. We surveyed people living in or near protected areas and people living away from protected areas in Nepal, to understand human attitudes towards red panda conservation. Given Nepal's participatory approach to managing protected areas, we hypothesized that local people living in or near protected areas would have more positive attitudes towards red panda conservation than those in non-protected areas. Ninety percent of the 142 respondents had positive attitudes, with people living in or near protected areas expressing less positive attitudes than those in non-protected areas. Despite this difference between protected and non-protected areas, people were generally positive towards red panda conservation. However, positive attitudes did not necessarily translate to sustainable resource-use behaviour. We found there was a high prevalence of both livestock grazing and livestock disease in red panda habitat. We suggest that alternative farming practices (e.g. stall-feeding of livestock) and awareness programmes (e.g. education on the conservation status and legal protection of red pandas, and livestock–wildlife disease transmission) could be important tools to improve conservation attitudes and protect red pandas in Nepal.
Although quality of life (QoL) is receiving increasing attention in bipolar disorder (BD) research and practice, little is known about its naturalistic trajectory. The dual aims of this study were to prospectively investigate: (a) the trajectory of QoL under guideline-driven treatment and (b) the dynamic relationship between mood symptoms and QoL.
In total, 362 patients with BD receiving guideline-driven treatment were prospectively followed at 3-month intervals for up to 5 years. Mental (Mental Component Score – MCS) and physical (Physical Component Score – PCS) QoL were measured using the self-report SF-36. Clinician-rated symptom data were recorded for mania and depression. Multilevel modelling was used to analyse MCS and PCS over time, QoL trajectories predicted by time-lagged symptoms, and symptom trajectories predicted by time-lagged QoL.
MCS exhibited a positive trajectory, while PCS worsened over time. Investigation of temporal relationships between QoL and symptoms suggested bidirectional effects: earlier depressive symptoms were negatively associated with mental QoL, and earlier manic symptoms were negatively associated with physical QoL. Importantly, earlier MCS and PCS were both negatively associated with downstream symptoms of mania and depression.
The present investigation illustrates real-world outcomes for QoL under guideline-driven BD treatment: improvements in mental QoL and decrements in physical QoL were observed. The data permitted investigation of dynamic interactions between QoL and symptoms, generating novel evidence for bidirectional effects and encouraging further research into this important interplay. Investigation of relevant time-varying covariates (e.g. medications) was beyond scope. Future research should investigate possible determinants of QoL and the interplay between symptoms and wellbeing/satisfaction-centric measures of QoL.
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.
Clozapine is an atypical antipsychotic agent used primarily in the management of treatment-resistant schizophrenia. Previous studies have demonstrated clozapine’s superior efficacy over other antipsychotic medications in treating this population of patients. The aim of this study was to assess if the number of hospital admissions and days spent in hospital reduced with the initiation of clozapine, compared with when the same sample of patients were prescribed other antipsychotics prior to clozapine initiation.
A mirror-image study design was adopted. In this case the intervention under study was the initiation of clozapine. Information was collected retrospectively from the charts of patients attending the University Hospital Galway clozapine clinic. The number of admissions and number of hospital days were collected for each patient over the 3 years before and after clozapine initiation. Wilcoxon’s signed-rank test was used to test for statistical significance.
The total sample size comprised of 62 patients, of which the majority were male (74.2%) and had a diagnosis of schizophrenia (82.3%). The mean dose of clozapine was 417 mg, and mean age of the sample was 38 years. Mean number of hospital admissions reduced from 2.8 to 0.8 (p<0.0001) following initiation of clozapine. Mean number of days spent in hospital reduced from 116.4 to 17.1 (p<0.0001).
After initiation of clozapine treatment, patients experience a substantial reduction in number of hospital admissions and number of days spent in hospital when compared with a similar period prior to clozapine initiation.
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.
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.
Abnormalities in the anterior inter-hemispheric connectivity have previously been implicated in major depressive disorder. Disruptions in fractional anisotropy in the callosum and fornix have been reported in schizophrenia and major depressive disorder. Oligodendrocyte density and overall size of the callosum and fornix show no alteration in either illness, suggesting that gross morphology is unchanged but more subtle organizational disruption may exist within these brain regions in mood and affective disorders.
Using high-resolution oil-immersion microscopy we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath, and using standard high-resolution light microscopy we measured the density of myelinated axons. These measurements were made in the genu of the corpus callosum and the medial body of the fornix at its most dorsal point. Measures were taken in the sagittal plane in the callosal genu and in the coronal plane at the most dorsal part of the fornix body.
Cases of major depressive disorder had significantly greater mean myelin cross-sectional area (p = 0.017) and myelin thickness (p = 0.004) per axon in the genu than in control or schizophrenia groups. There was no significant change in the density of myelinated axons, and no changes observed in the fornix.
The results suggest a clear increase of myelin in the axons of the callosal genu in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin.
The Vulnerable red panda Ailurus fulgens is endemic to the Himalayas. Anthropogenic activities, including deforestation, have degraded the species’ habitat but the effects of livestock have not been examined. We assessed the effects of illegal livestock activity on the presence of the red panda in Rara National Park, Nepal. The probability of detecting red panda faecal pellets decreased with livestock occurrence but not with elevation or aspect. The presence of bamboo and proximity to water are important to red pandas but did not influence their habitat use at the spatial resolution evaluated. Livestock grazing in Rara National Park appears to adversely affect the presence of the red panda within its habitat. To reduce illegal livestock grazing we recommend enforcement of existing regulations, that training workshops be held for herders, and awareness-raising and dialogue with residents.
Post-traumatic stress disorder (PTSD) in response to the World Trade Center (WTC) disaster of 11 September 2001 (9/11) is one of the most prevalent and persistent health conditions among both professional (e.g. police) and non-traditional (e.g. construction worker) WTC responders, even several years after 9/11. However, little is known about the dimensionality and natural course of WTC-related PTSD symptomatology in these populations.
Data were analysed from 10 835 WTC responders, including 4035 police and 6800 non-traditional responders who were evaluated as part of the WTC Health Program, a clinic network in the New York area established by the National Institute for Occupational Safety and Health. Confirmatory factor analyses (CFAs) were used to evaluate structural models of PTSD symptom dimensionality; and autoregressive cross-lagged (ARCL) panel regressions were used to examine the prospective interrelationships among PTSD symptom clusters at 3, 6 and 8 years after 9/11.
CFAs suggested that five stable symptom clusters best represent PTSD symptom dimensionality in both police and non-traditional WTC responders. This five-factor model was also invariant over time with respect to factor loadings and structural parameters, thereby demonstrating its longitudinal stability. ARCL panel regression analyses revealed that hyperarousal symptoms had a prominent role in predicting other symptom clusters of PTSD, with anxious arousal symptoms primarily driving re-experiencing symptoms, and dysphoric arousal symptoms primarily driving emotional numbing symptoms over time.
Results of this study suggest that disaster-related PTSD symptomatology in WTC responders is best represented by five symptom dimensions. Anxious arousal symptoms, which are characterized by hypervigilance and exaggerated startle, may primarily drive re-experiencing symptoms, while dysphoric arousal symptoms, which are characterized by sleep disturbance, irritability/anger and concentration difficulties, may primarily drive emotional numbing symptoms over time. These results underscore the importance of assessment, monitoring and early intervention of hyperarousal symptoms in WTC and other disaster responders.
Surface-enhanced Raman spectroscopy (SERS) is highly dependent upon the substrate, where excitation of the localized metal surface plasmon resonance enhances the vibrational scattering signal of proximate analyte molecules. This article reviews recent progress in the fabrication of SERS substrates and the requirements for characterization of plasmonic materials as SERS platforms. We discuss bottom-up fabrication of SERS substrates and illustrate the advantages of rational control of metallic nanoparticle synthesis and assembly for hot spot creation. We also detail top-down methods, including nanosphere lithography for the preparation of tunable, highly sensitive, and robust substrates, as well as the unique benefits of tip-enhanced Raman spectroscopy for simultaneous acquisition of molecular vibrational information and high spatial resolution imaging. Finally, we discuss future prospects and challenges in SERS, including the development of surface-enhanced femtosecond stimulated Raman spectroscopy, microfluidics with SERS, creating highly reproducible substrates, and the need for reliable characterization of substrates.
Longitudinal symptoms of post-traumatic stress disorder (PTSD) are often characterized by heterogeneous trajectories, which may have unique pre-, peri- and post-trauma risk and protective factors. To date, however, no study has evaluated the nature and determinants of predominant trajectories of PTSD symptoms in World Trade Center (WTC) responders.
A total of 10835 WTC responders, including 4035 professional police responders and 6800 non-traditional responders (e.g. construction workers) who participated in the WTC Health Program (WTC-HP), were evaluated an average of 3, 6 and 8 years after the WTC attacks.
Among police responders, longitudinal PTSD symptoms were best characterized by four classes, with the majority (77.8%) in a resistant/resilient trajectory and the remainder exhibiting chronic (5.3%), recovering (8.4%) or delayed-onset (8.5%) symptom trajectories. Among non-traditional responders, a six-class solution was optimal, with fewer responders in a resistant/resilient trajectory (58.0%) and the remainder exhibiting recovering (12.3%), severe chronic (9.5%), subsyndromal increasing (7.3%), delayed-onset (6.7%) and moderate chronic (6.2%) trajectories. Prior psychiatric history, Hispanic ethnicity, severity of WTC exposure and WTC-related medical conditions were most strongly associated with symptomatic trajectories of PTSD symptoms in both groups of responders, whereas greater education and family and work support while working at the WTC site were protective against several of these trajectories.
Trajectories of PTSD symptoms in WTC responders are heterogeneous and associated uniquely with pre-, peri- and post-trauma risk and protective factors. Police responders were more likely than non-traditional responders to exhibit a resistant/resilient trajectory. These results underscore the importance of prevention, screening and treatment efforts that target high-risk disaster responders, particularly those with prior psychiatric history, high levels of trauma exposure and work-related medical morbidities.
Long-term tillage and fertilizer experiments were conducted in rice in kharif followed by lentil in dry subhumid Inceptisols at Varanasi and Faizabad; horse gram at Phulbani and linseed at Ranchi in moist subhumid Alfisols in rabi during 2001 to 2010. The study was conducted to assess the effect of conventional tillage (CT), low tillage + interculture (LT1) and low tillage + herbicide (LT2) together with 100% N (organic) (F1), 50% N (organic) + 50% N (inorganic) (F2) and 100% N (inorganic) (F3) on productivity, profitability, rainwater and energy use efficiencies. The results at Varanasi revealed that CT was superior with mean yield of 2389 kg ha−1, while F1 was superior with 2378 kg ha−1 in rice. At Faizabad, CT was superior with mean rice yield of 1851 kg ha−1 and lentil yield of 977 kg ha−1, while F1 was superior with 1704 and 993 kg ha−1 of rice and lentil, respectively. At Phulbani, F2 was superior with rice yield of 1170 kg ha−1. At Ranchi, F2 with rice yield of 986 kg ha−1 and F3 with linseed yield of 224 kg ha−1 were superior. The regression model of crop seasonal rainfall and yield deviations indicated an increasing trend in rice yield over mean (positive deviation) with increase in rainfall at all locations; while a decreasing trend (negative deviation) was found for lentil at Faizabad, horse gram at Phulbani and linseed at Ranchi. Based on economic analysis, CTF1 at Varanasi and Faizabad, CTF2 at Phulbani and LT2F2 at Ranchi were superior.
India is the second most populous nation in the world after China, and its plant genetic resources are an important basis for crop improvement to meet human population needs. An important legume in the diet of the Indian population is common bean (Phaseolus vulgaris L.). Common beans are one of the many important legumes grown in India, but unlike others, its centre of origin is not in Asia but in the Americas. The objective of this study was to evaluate two collections of Indian common beans: one for an internationally available collection of Food and Agriculture Organization (FAO)-protected accessions and one from the north-western Himalayan region. In total, 149 Indian landraces were evaluated with a total of 24 microsatellites across the two collections, and these represented all common bean-growing states of India. A population structure analysis was used to find groups in each collection, and this was compared across the collections. The genetic analysis of the two sets of Indian accessions with neighbour-joining trees and principal component analysis categorized the landraces into Andean and Mesoamerican gene pool groups. The Andean genotypes dominated the north-western Himalayan collection while the FAO-protected accessions were predominantly Mesoamerican. The Indian subcontinent can be considered as a region of high bean diversity; however, very little introgression was observed between the gene pools in both the germplasm sets. Gene pool identity was further substantiated by the comparison of seed traits, particularly seed size. The role of the landraces in plant breeding programmes is discussed.