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To assess the effect of tranexamic acid in head and neck surgical procedures.
A prospective, double-blind and randomised, parallel group, placebo-controlled clinical trial was conducted. Ninety-two patients undergoing various head and neck surgical procedures were randomised. Subjects received seven infusions of coded drugs (tranexamic acid or normal saline) starting at the time of skin closure. Haematological, biochemical, blood loss and other parameters were observed by the staff, who were blinded to patients’ group allocation (case or control).
Patients were analysed on the basis of type of surgery. Fifty patients who had undergone surgical procedures, including total thyroidectomy, total parotidectomy, and various neck dissections with or without primary tumour excision, were included in the first group. The second group comprised 41 patients who had undergone hemithyroidectomy, lobectomy or superficial parotidectomy. There was no statistical difference in blood parameters between both groups. There was a reduction in post-operative drain volume, but this was not significant.
Although this prospective, randomised, placebo-controlled clinical trial found a reduction in post-operative drain volume in tranexamic acid groups, the difference was not statistically significant between the various head and neck surgical procedure groups.
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.
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.
Introduction: A previous Canadian emergency department (ED) model determined predictors of increased workload using a manual chart review to elucidate comorbidities. We designed an electronic algorithm to capture all comorbidities based on the Charlson Comorbidity Index (CCI) for a 5 year period preceding the ED visit from the regional inpatient database. Our objective was to identify predictors correlating with physician time require to treat patients and thus develop a multivariable model to predict physician workload. Methods: From May to September 2015, two research assistants (RAs) shadowed a random sample of physicians from the six urban EDs in a single health region. They documented time spent performing clinical and non-clinical functions for patient visits. A linkage with the previously validated regional ED database was used to obtain triage acuity, age, gender, mode of arrival, and CCI scores. Multiple linear regression was used to describe the associations between predictor variables and total physician time per patient visit as well as time spent on history and physical exam and to derive an equation for physician workload. RA inter-rater reliability was assessed on 107 MD-patient interactions. Results: Over the 4-month period, 873 patient encounters were documented. Data from 599 completed encounters were included in the model. The median age was 49.4 (SD 22.8) and 52.2% were female. Overall, 16.0% were admitted to hospital, 64.9% of patients were CTAS 1-3, 19.6% of patients arrived by ambulance, and 15.5% of patients had a CCI score of ≥ 1. The mean time spent on history and physical was 7.0 minutes (SD 4.73) and mean total time was 19.4 minutes (SD 11.6). Using a linear regression model with total time as the dependent and EMS arrival, CTAS, and age as the independent variables, having any CCI score is a significant predictor of total time (p = 0.03). with a difference of 2.9 minutes between CCI positive versus negative patients. Higher acuity was the most significant factor associated with time spent with a mean difference of 4.4 minutes per CTAS category. The intraclass correlation coefficient value was 0.99 (95% CI 0.97-1.00) indicating excellent reliability. Conclusion: The electronically derived CCI does have value in the development of a physician workload model and can replace the use of manual chart review to define patient comorbidities.
Introduction: ED patient comorbidity is difficult to ascertain for research. Traditional surrogates such as triage acuity, admission rate, and age have been used to approximate patient complexity. Differences between EDs for the management of similar conditions are nevertheless difficult to reconcile. The Charlson Comorbidity Index (CCI) contains 19 categories and is a validated predictor of the ten-year mortality for a patient who may have a range of comorbid conditions. CCI is based on the International Classification of Diseases (ICD) diagnosis codes found in administrative data such as the Discharge Abstract Database (DAD). The DAD collects this, and other inpatient information, for all Canadian hospitals. We sought to develop a linkage between the regional ED database and the regional inpatient DAD in order to derive a CCI score for each ED patient as a surrogate of comorbidity. Methods: We used regional data from Vancouver Coastal Health (VCH) over a 2.5 year period from April 2013 - September 2015. An algorithm was created to identify CCI conditions in the regional DAD. Whenever a patient visited the ED a query was made to the DAD going back for 5 years to acquire CCI relevant diagnoses and enter these diagnoses as well as the CCI weighting into the ED database. Patient DAD records from VCH were utilized no matter in which ED a patient presented. No information from admissions outside the region was available. Results: There were 931,596 regional ED visits made by 446,579 unique patients in a total of 11 EDs (6 urban and 5 rural). In total there were 127,233 patients with a CCI score (13.7% of total visits). The average CCI was 0.40 (SD 1.31) with a range of 0.12 at the urban urgent care centre to 0.52 at the urban tertiary care centre. More isolated rural EDs tended to have higher percentages of patients with CCI scores than community urban EDs. Higher acuity, age, and ambulance arrival, ED death, all correlated to higher CCI scores. The most common CCI conditions were “diabetes with complications” (10/11 EDs) and was present in 35,816 (3.8%) visits and “cancer” (10/11 EDs) present in 34,624 (3.7%) ahead of COPD (26,451 visits) and CHF (25,233 visits). Conclusion: Use of the CCI is a novel way to passively capture patient comorbidities without reliance on a data entry technician. Limitations include the inability to link to hospitalization data outside a specific health region.
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.
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.
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.
Aspiration pneumonia is an important cause of death in head and neck cancer patients. This study therefore aimed to evaluate the risk factors associated with aspiration pneumonia in head and neck cancer patients.
Hospital death records from 12 years (2000–2012) were reviewed to obtain the number of deaths. Treatment details and cause of death were analysed. Statistical analysis was performed to identify the risk factors for aspiration pneumonia.
The records revealed that aspiration pneumonia was the cause of death in 51 out of 85 patients. Primary tumour site (oropharynx and hypopharynx, odds ratio 3.3; 95 per cent confidence interval 1.17–9.4, p = 0.02) and advanced tumour stage (odds ratio 4.2, 95 per cent confidence interval 1.16–15.61, p = 0.02) had significant negative impacts on aspiration pneumonia related mortality.
Advanced pharyngeal cancer patients are at an increased risk of aspiration pneumonia related death. Investigations for the early detection of this condition are recommended in these high-risk patients.
There is increasing evidence that Mars may have once been a habitable environment. Gypsum is targeted in the search for Martian biosignatures because it can host extensive cryptoendolithic communities in extreme terrestrial environments and is widespread on Mars. In this study the viability of using different spectroscopy-based techniques to identify the presence of gypsum endolithic communities was investigated by analysing various cryptoendoliths collected from the Lake St. Martin impact crater (LSM), a Mars analogue site found in Manitoba, Canada. Concurrently, the cryptoendolithic microbial community structure present was also analysed to aid in assigning spectroscopic features to microbial community members. Two main morphologies of endolithic communities were collected from gypsum deposits at LSM: true cryptoendolithic communities and annular deposits on partially buried boulders and cobbles <1 cm below the soil surface. Endolithic communities were found to be visibly present only in gypsum with a high degree of translucency and could occur as deep as 3 cm below the exterior surface. The bacterial community was dominated by a phylum (Chloroflexi) that has not been previously observed in gypsum endoliths. The exterior surfaces of gypsum boulders and cobbles are devoid of spectroscopic features attributable to organic molecules and detectable by reflectance, Raman, or ultraviolet-induced fluorescence spectroscopies. However, exposed interior surfaces show unique endolithic signatures detectable by each spectroscopic technique. This indicates that cryptoendolithic communities can be detected via spectroscopy-based techniques, provided they are either partially or fully exposed and enough photon–target interactions occur to enable detection.
Plant genetic resources are raw materials and their use in breeding is one of the most sustainable ways to conserve biodiversity. The ICRISAT has over 120,000 accessions of its five mandate crops and six small millets. The management and utilization of such large diversity are greatest challenges to germplasm curators and crop breeders. New sources of variations have been discovered using core and minicore collections developed at the ICRISAT. About 1.4 million seed samples have been distributed; some accessions with specific attributes have been requested more frequently. The advances in genomics have led researchers to dissect population structure and diversity and mine allelic variations associated with agronomically beneficial traits. Genome-wide association mapping in sorghum has revealed significant marker–trait associations for many agronomically beneficial traits. Wild relatives harbour genes for resistance to diseases and insect pests. Resistance to pod borer in chickpea and pigeonpea and resistance to rust and late leaf spot in groundnut have been successfully introgressed into a cultivated genetic background. Synthetics in groundnut are available to broaden the cultigen's gene pool. ICRISAT has notified the release of 266 varieties/cultivars, germplasm, and elite genetic stocks with unique traits, with some having a significant impact on breeding programs. Seventy-five germplasm lines have been directly released for cultivation in 39 countries.
Three Critically Endangered Gyps vultures endemic to South Asia continue to decline due to the use of diclofenac to treat livestock. High nephrotoxicity of diclofenac to Gyps vultures, leading to death, has been established by experiment and observation, in four out of five Gyps vulture species which occur in South Asia. Declines have also been observed in South Asia’s four other non-Gyps vulture species, but to date there has been no evidence about the importance of diclofenac as a potential cause. Neither is there any evidence on the toxicity of diclofenac to the Accipitridae other than vultures. In this study, gross and microscopic lesions and diclofenac tissue levels in Steppe Eagles Aquila nipalensis found at a cattle carcass dump in Rajasthan, India, show evidence of the toxicity of diclofenac for this species. These findings suggest the possibility that diclofenac is toxic to other accipitrid raptors and is therefore a potential threat to much wider range of scavenging species in South Asia.
Hardness is a measure of the resistance of a material to be penetrated and eroded by
sharp projections of other materials such as diamond. The process of creating sharp
projections on any test surface is known as indentation. Hardness measurement of any
material is the result of a complex process of deformation during indentation. The
indenter tip geometry, which includes radius of curvature at the tip and tip angle,
affects the hardness measurement by influencing the nature of the penetration process on
the test surface, because every indenter deforms the specimen surface with a different
geometry. The controlled indenter geometry can improve the consistency of hardness
measurement. In this paper we report the estimation of two important geometrical
parameters, radius of curvature and tip angle of a Rockwell indenter by using a simple
method of image processing and compare the results with those obtained with a traceable 3D
optical profiler. Evaluation of uncertainty in measuremts is carried out as per ISO
guidelines (ISO-GUM) and a detailed uncertainty budget is presented. The tip angle
estimted is 119.95 degree. The radius of curvature is estimted to be 199.96 ± 0.80μm by image analysis which
agrees well with the value estimated by using optical profiler i.e. 199.12 μm.
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.
In view of the mandate from the World Health Organization (WHO) for developing novel drug candidates against human lymphatic filariasis, dihydrofolate reductase (DHFR) inhibitors are explored as potential antifilarial agents. The in vitro biological evaluation of an in-house library of 12 diverse antifolate compounds with 2,4-diaminopyrimidine and 2,4-diamino-s-triazine structural features against Brugia malayi is reported. To confirm the DHFR inhibitory potential of these compounds, reversal studies using folic acid and folinic acid were undertaken. Inhibition of DHFR can induce apoptosis; in this light, preliminary evidence of apoptosis by test compounds was detected using ethidium bromide–acridine orange staining and the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition assay. Among the evaluated compounds, 3 showed significant activity against both microfilariae and adult worms. The effects of 2 of these compounds were mostly reversed by folic acid, validating DHFR inhibitory activity. Partial reversal of the effect of 2 compounds by folinic acid and non-reversal of the effect of the third compound both by folic and folinic acids are discussed. This study opens new avenues for the discovery of lead molecules by exploiting the folate pathway against one of the major neglected tropical diseases, filariasis.
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.