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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.
Background: Pediatric craniocerebral gunshot wounds occur in the context of both accidental and intentional trauma. Unique physiologic factors merited research into prognostic factors and treatment priorities in the pediatric population. Methods: A systematic search of MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Registered Trials and Systematic Reviews, ISRCTN, and ClinicalTrials.gov was conducted. Selection criteria included all studies published in any language since 2000 which described intracranial isolated gunshot wounds in a civilian individual or population of pediatric age. Post-mortem and epidemiological studies were excluded. Screening was conducted through Covidence. Results: Initial database search revealed 349 unique studies for abstract and title screening. Fifty studies were selected for full text screening. Nine studies were included in the final review. Study quality was assessed with the Newcastle-Ottawa Scale. Case series noted bullet migration, pituitary deficiency, neurovascular and neuropsychological concerns. Three single-center retrospective studies of 71, 30, and 48 pediatric patients suggested multiple negative prognostic signs on initial presentation. Early aggressive surgical treatment was recommended by some authors. Conclusions: This systematic review analyzed the best current understanding of evidence for prognostic factors and treatment considerations of intracranial gunshot wounds in the pediatric neurotrauma context. Areas for future research with larger multi-center studies were highlighted.
Manipur, an international border region has the highest incidence of human immunodeficiency virus (HIV)-1 infection in India. Nevertheless, there have been no analytical reviews of research article published within this region. In this review, the authors aim to draw the attention of policy makers, medical practitioners and researchers in adopting new strategies to limit the expansion of HIV/acquired immunodeficiency syndrome (AIDS) not only in Manipur but also in other international border areas. A systematic search for published literature in last decade was performed based on the keywords ‘Manipur’ and ‘HIV’ using the PubMed. Twenty-six articles were selected and reviewed. There were high incidence of drug resistance (53%), emergence of recombinant virus (32%) and increased incidence of co-infection with hepatitis C virus. The prime cause of the HIV is due to the uses of ‘heroin’ smuggled from the ‘South Asia Golden Triangle’ and complex patterns of cross-border movement for trade and commerce. The drug abuse, social stigma, geographical location and resource limitation and socio-political problem of the region have contributed strongly on spreading and failure of preventively programme of HIV/AIDS. This review will provide vital knowledge for the policy makers and clinicians for sentinel surveillance of AIDS pandemic in Manipur and other international border regions.
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.
It is known that given a set X of m (⩾n) distinct real numbers and a real-valued function f denned on X, there exists a unique polynomial pn-1,f,x of degree n — 1 or less which approximates best to f(x) on X, that is, which minimizes the deviation δ = δ(f, p) defined by the αth-power metric (α < 1) with positive weights, or by the positively weighted maximum of |f — p| on X; these deviations shall be denoted by δα and δβ. The polynomial pn-1,f,x has the property that f — pn-1,f,x has at least n strong sign changes; in other words, there are at least n + 1 points in X where the difference takes alternatingly positive and negative values.
Stereotactic body radiotherapy (SBRT) is widely used for the treatment of stage-I non-small cell lung cancer (NSCLC). Patient-specific motion correlated with 4DCT could be essential for hypofractionated SBRT. All patients undergoing SBRT do not require motion management during the dose delivery. The objective of this study was to evaluate which patient may benefit from Gated SBRT.
Materials and methods
Treatment planning of 20 patients of stage-I NSCLC was analysed. Conventional and 4DCT scans were taken. Internal target volume as well as planning target volume (ITV and PTV) were determined in the CT data sets. PTVall phases created using 4DCT data sets and PTV15mm created using conventional CT data were compared. Also, ITVall phases were compared with ITV created from maximum intensity projections (ITVMIP). Suitability of patients for motion management-based treatment delivery was also evaluated.
The average ITVMIP to ITVall phases ratio is 1·06 indicating good agreement between them. Based on the ratio of intensity projections, 9 out of 17 patients were found suitable for our existing gated treatment.
4D CT is the main requirement in SBRT to identify the patients who can benefit from motion management during the dose delivery.
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.
The study primarily aimed to calculate the orientation of the cochlea pre-operatively, using high-resolution computed tomography of the temporal bone, and predict the ease of electrode insertion.
Pre-operatively, high-resolution computed tomography scans were conducted on children scheduled for cochlear implantation, and two angles, α and β, were calculated. The values of α and β were then correlated with intra-operative difficulty in insertion of the electrode array.
Ninety-six children were included in the study. Of the seven patients who had an α angle of less than 50 degrees, the surgeon experienced difficulties in electrode insertion. However, there were four patients with an α angle of more than 50 degrees for whom the surgeon also experienced difficulties in electrode insertion. In all these patients, the β angle was more than 20 degrees.
Calculation of cochlear orientation and its angle with the surgical axis (α and β) can aid the planning of surgery, particularly with regard to the cochleostomy site and preservation of residual hearing.
Rice has the lowest grain protein content (GPC) among cereals. Efforts have been made to improve GPC through the modified bulk-pedigree method of selection. A total of 1780 F8 recombinant lines were derived in the year 2013 from five different cross combinations involving two high-GPC landraces, namely ARC10075 and ARC10063, three high-yielding parents, namely Swarna, Naveen and IR64, and one parent, namely Sharbati, known for superior grain quality with high micronutrient content. Near-infrared spectroscopy was used to facilitate high-throughput selection for GPC. Significant selection differential, response to selection and non-significant differences between the predicted and observed response to selection for GPC and protein yield indicated the effectiveness of this selection process. This resulted in lines with high GPC, protein yield and desirable levels of amylose content. Further, based on high mean and stability for GPC and protein yield over the environments in the wet seasons of 2013, 2014 and the dry season of 2014, 12 elite lines were identified. Higher accumulation of glutelin fraction and non-significant change in prolamin/glutelin ratio in the grain suggested safe guarding of the nutritional value of rice grain protein of most of these identified lines. Since rice is the staple food of millions, the output of breeding for high GPC could have a significant role in alleviating protein malnutrition, especially in the developing world.
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.
We study the abundance of the remnants of stars that reionized the Universe in galaxies in the present day Universe using the eagle cosmological hydrodynamical simulation. High mass galaxies contain most of these ‘reionizers’. The fractional number of galaxies that do not host reionizers increases with decreasing stellar mass, M⋆. For the galaxies that host reionizers, the fraction of mass of the galaxy in reionizers increases with decreasing M⋆, such that the fraction is low (~10−4) for high mass galaxies and can be as high as 0.1 in low mass galaxies, M⋆ ≤ 107 M⊙. In Milky-Way like galaxies, the distribution of reionizers is spatially more extended than that of normal stars.
This study explored how coping with war-related traumatic events in Sierra Leone impacted mental health outcomes among 529 youth (aged 10–17 at baseline; 25% female) using longitudinal data from three time points (Time 1 in 2002, Time 2 in 2004, and Time 3 in 2008). We examined two types of coping items (approach and avoidance); used multiple regression models to test their relations with long-term mental health outcomes (internalizing behaviors, externalizing behaviors, adaptive/prosocial behaviors, and posttraumatic stress symptoms); and used mediation analyses to test whether coping explained the relation between previous war exposures (being raped, death of parent(s), or killing/injuring someone during the war) and those outcomes. We found that avoidance coping items were associated with lower internalizing and posttraumatic stress behaviors at Time 3, and provided some evidence of mediating the relation between death of parent(s) during the war and the two outcomes mentioned above. Approach coping was associated with higher Time 3 adaptive/prosocial behaviors, whereas avoidance coping was associated with lower Time 3 adaptive/prosocial behaviors. Avoidance coping may be a protective factor against mental illness, whereas approach coping may be a promotive factor for adaptive/prosocial behaviors in war-affected societies. This study has important implications for designing and implementing mental health interventions for youth in postconflict settings.
Lower and middle income countries (LMICs) are home to >80% of the global population, but mental health researchers and LMIC investigator led publications are concentrated in 10% of LMICs. Increasing research and research outputs, such as in the form of peer reviewed publications, require increased capacity building (CB) opportunities in LMICs. The National Institute of Mental Health (NIMH) initiative, Collaborative Hubs for International Research on Mental Health reaches across five regional ‘hubs’ established in LMICs, to provide training and support for emerging researchers through hub-specific CB activities. This paper describes the range of CB activities, the process of monitoring, and the early outcomes of CB activities conducted by the five research hubs.
The indicators used to describe the nature, the monitoring, and the early outcomes of CB activities were developed collectively by the members of an inter-hub CB workgroup representing all five hubs. These indicators included but were not limited to courses, publications, and grants.
Results for all indicators demonstrate a wide range of feasible CB activities. The five hubs were successful in providing at least one and the majority several courses; 13 CB recipient-led articles were accepted for publication; and nine grant applications were successful.
The hubs were successful in providing CB recipients with a wide range of CB activities. The challenge remains to ensure ongoing CB of mental health researchers in LMICs, and in particular, to sustain the CB efforts of the five hubs after the termination of NIMH funding.
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.
Expressed sequence tag-simple sequence repeat (EST-SSR) markers were used to analyse genetic diversity among three Lens species. The SSR loci amplified successfully in wild species, with 94·82% transferability in Lens culinaris subsp. orientalis, 95·4% in Lens nigricans, 98·81% in L. culinaris subsp. odemensis, 94·82% in L. culinaris subsp. tomentosus and 96·55% in Lens ervoides. Ninety-nine alleles (average 3·41 alleles/locus) were detected by 29 SSR markers. Based on the unweighted pair group method with arithmetic mean cluster analysis, all the genotypes were grouped into three clusters at a similarity level of 0·30. The diversity analysis indicated no species-specific clustering of the wild and cultivated species. Wild species L. nigricans and L. culinaris subsp. odemensis, L. culinaris subsp. orientalis and L. ervoides were grouped in Cluster I, whereas the Mediterranean land races of L. culinaris subsp. culinaris and L. culinaris subsp. tomentosus formed a separate group in Cluster II A. Cluster II B comprised L. ervoides, L. culinaris subsp. orientalis and L. culinaris subsp. culinaris. Clusters II C, II D and II F included cultivated Indian lentil genotypes. Cluster II E comprised Indian and Mediterranean germplasm lines. Cluster II F included three early maturing germplasm lines, whereas Cluster III included only two germplasm lines. The functional annotation of SSR-containing unigenes revealed that a majority of genes were involved in an important transport-related function or were a component of metabolic pathways. A high level of polymorphism of EST-SSRs and their transferability to related wild species indicated that these markers could be used for molecular screening, map construction, comparative genomic studies and marker-assisted selection.
We present the updated glaciological mass balance (MB) of Chhota Shigri Glacier, the longest continuous annual MB record in the Hindu-Kush Karakoram Himalaya (HKH) region. Additionally, 4 years of seasonal MBs are presented and analyzed using the data acquired at an automatic weather station (AWS-M) installed in 2009 on a lateral moraine (4863ma.s.l.). The glaciological MB series since 2002 is first recalculated using an updated glacier hypsometry and then validated against geodetic MB derived from satellite stereo-imagery between 2005 (SPOT5) and 2014 (Pléiades). Chhota Shigri Glacier lost mass between 2002 and 2014 with a cumulative glaciological MB of –6.72mw.e. corresponding to a mean annual glacier-wide MB (Ba) of –0.56mw.e. a–1. Equilibrium-line altitude (ELA0) for the steady-state condition is calculated as ~4950ma.s.l., corresponding to an accumulation–area ratio (AAR0) of ~61%. Analysis of seasonal MBs between 2009 and 2013 with air temperature from AWS-M and precipitation from the nearest meteorological station at Bhuntar (1050ma.s.l.) suggests that the summer monsoon is the key season driving the interannual variability of Ba for this glacier. The intensity of summer snowfall events controls the Ba evolution via controlling summer glacier-wide MB (Bs).
This paper presents modifications to powered endoscopic dacryocystorhinostomy without stenting for the management of acquired nasolacrimal duct obstruction.
A retrospective, non-randomised review.
A total of 105 patients with epiphora secondary to acquired nasolacrimal duct obstruction were operated on by our modified powered endoscopic dacryocystorhinostomy approach.
Of 105 patients, 100 (95.2 per cent) have remained asymptomatic. One patient with a narrow ostium had improved symptoms, while four patients continued to experience persistent symptoms (treatment failures).
The modified powered endoscopic dacryocystorhinostomy approach led to excellent results, without bone exposure and granulations, and with early mucosalisation.
To evaluate the effect of body mass index and neck length on endotracheal tube movement during neck extension in thyroidectomy.
A prospective study was conducted of 30 patients undergoing thyroidectomy during an 8-month period. Patient characteristics were recorded and endotracheal tube displacement was determined.
Mean body mass index was 27.8 kg/m2 (range, 17.5–34.7 kg/m2) and mean neck circumference was 43.2 cm (range, 28–56 cm). The mean (± standard deviation) upward displacement of the endotracheal tube during neck extension was 7.17 ± 5.87 mm. Patients with a larger body mass index had a significantly greater amount of tube displacement (R2 = 0.67, p < 0.0001), as did patients with a smaller neck length (R2 = 0.48, p < 0.0001).
Neck extension results in upward displacement of the endotracheal tube. The amount of displacement is significantly higher in patients with a larger body mass index or shorter neck length. This has particular relevance for nerve monitoring in thyroidectomy.
Stem cell therapy has the optimistic goal of regenerating the myocardium as defined by re-growth of lost or destroyed myocardium. As applied to patients with heart failure, many confuse or limit the regenerative definition to just improving myocardial function and/or decreasing myocardial scar formation, which may not be the most important clinical outcome to achieve in this promising field of molecular medicine. Many different stem cell-based therapies have been tested and have demonstrated a safe and feasible profile in adult patients with heart failure, but with varied efficacious end points reported. Although not achieved as of yet, the encompassing goal to regenerate the heart is still believed to be within reach using these cell-based therapies in adult patients with heart failure, as the first-generation therapies are now being tested in different phases of clinical trials. Similar efforts to foster the translation of stem cell therapy to children with heart failure have, however, been limited. In this review, we aim to summarise the findings from pre-clinical models and clinical experiences to date that have focussed on the evaluation of stem cell therapy in children with heart failure. Finally, we present methodological considerations pertinent to the design of a stem cell-based trial for children with heart failure, as they represent a population of patients with very different sets of issues when compared with adult patients. As has been taught by many learned clinicians, children are not small adults!