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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.
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.
Background: The role of extent of surgical resection (EOR) on clinical outcomes in patients with low-grade glioma requires further examination. Methods: We systematically searched MEDLINE, Embase, and the Cochrane Library for studies published between January 1, 1990 and January 5, 2018 on predefined patient outcomes regarding different EOR of low-grade glioma. Results: Our literature search yielded 60 studies including 13,289 patients. Pooled estimates of overall survival showed an increase from 3.79 years (95% CI, 2.37–5.22) in the biopsy group to 6.68 years (95% CI, 4.19–9.16) in STR to 10.65 years (95% CI, 6.78–14.52) in GTR. When compared to STR, GTR prolonged progression-free survival by 2.08 years (95% CI, 0.26–3.89; P=0.025). Pooled estimates of seizure control showed an improvement from 47.8% (95% CI, 26.7–69.6) with biopsy to 54.2% (95% CI, 48.7–59.6) with STR to 81.0% (95% CI, 74.6–86.2) with GTR. Compared to STR, GTR delayed malignant transformation (RR, 0.43; 95% CI, 0.20–0.93; P=0.032), without increasing postoperative mortality (RR, 0.38; 95% CI, 0.07–1.97; P=0.250) or morbidity (RR, 1.22; 95% CI, 0.65–2.28; P=0.540). Conclusions: Among patients with low grade gliomas, higher degrees of safe EOR, were associated with longer overall and progression-free survival, better seizure control, and delayed malignant transformation, without increased mortality or morbidity.
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 merits of solar coronal at metric-wavelength (MW) radio have long been recognised (e.g. Pick and Vilmer, 2008). High-fidelity solar radio imaging at these frequencies has however remained challenging. On the one hand, dealing with the small spectral and temporal scales of variation in solar radio emission requires a data product capable of tracking the emission simultaneously across time, frequency and morphology. The Fourier imaging nature of interferometry, on the other hand, severely limits the instrumental ability to gather sufficient information to do this with the required fidelity and resolution. Benefiting from the enormous advances in technology the new generation of instruments, like the Murchison Widefield Array (MWA; Tingay et al. (2013), Bowman et al. (2013)), represent a quantum leap in our ability to gather data suitable for radio solar physics.
An improved understanding of the solar corona is crucial for making progress on long-standing problems like coronal heating and the origin of the solar wind. Metrewave radio emissions arise in the coronal regions and form a unique diagnostic probe of this, otherwise hard to study region. The background radio emission at these wavelengths comes from the slowly varying thermal free-free emission and on it are superposed a variety of nonthermal emissions arising from a range of plasma emission processes. The latter are coherent in nature and hence lead to a much larger observational contrast, as compared to that in EUV or X-ray, for emissions involving similar energetics. One of the prevalent hypotheses for explaining coronal heating is based on the presence of an energetically weak population of ‘nanoflares’ (Parker 1988). A necessary requirement for nanoflares based coronal heating to be effective is that their occurrence rate slopes must be <-2 (Hudson 1991). There is hence a lot of interest in studies of weak nonthermal emissions. Existing studies in EUV and X-ray bands have detected ‘microflares’ with slopes >-2 (e.g. Hannah et al. 2011). Some of the weak meterwave emissions detected are, however, believed to correspond to energies in the ‘picoflare’ range (Ramesh et al. 2013). It is hence, very interesting to study weak nonthermal emissions at metric wavelengths.
To determine whether antimicrobial-impregnated textiles decrease the acquisition of pathogens by healthcare provider (HCP) clothing.
We completed a 3-arm randomized controlled trial to test the efficacy of 2 types of antimicrobial-impregnated clothing compared to standard HCP clothing. Cultures were obtained from each nurse participant, the healthcare environment, and patients during each shift. The primary outcome was the change in total contamination on nurse scrubs, measured as the sum of colony-forming units (CFU) of bacteria.
PARTICIPANTS AND SETTING
Nurses working in medical and surgical ICUs in a 936-bed tertiary-care hospital.
Nurse subjects wore standard cotton-polyester surgical scrubs (control), scrubs that contained a complex element compound with a silver-alloy embedded in its fibers (Scrub 1), or scrubs impregnated with an organosilane-based quaternary ammonium and a hydrophobic fluoroacrylate copolymer emulsion (Scrub 2). Nurse participants were blinded to scrub type and randomly participated in all 3 arms during 3 consecutive 12-hour shifts in the intensive care unit.
In total, 40 nurses were enrolled and completed 3 shifts. Analyses of 2,919 cultures from the environment and 2,185 from HCP clothing showed that scrub type was not associated with a change in HCP clothing contamination (P=.70). Mean difference estimates were 0.118 for the Scrub 1 arm (95% confidence interval [CI], −0.206 to 0.441; P=.48) and 0.009 for the Scrub 2 rm (95% CI, −0.323 to 0.342; P=.96) compared to the control. HCP became newly contaminated with important pathogens during 19 of the 120 shifts (16%).
Antimicrobial-impregnated scrubs were not effective at reducing HCP contamination. However, the environment is an important source of HCP clothing contamination.
Three radio telescopes operating at 103 MHz are being installed at Ahmedabad, Rajkot and Surat separated by about 200 km from each other for observing interplanetary scintillations (IPS) of compact radio sources for study of solar wind plasma dynamics as well as radio source size measurements for cosmological studies. Of these, two radio telescopes at Ahmedabad and Rajkot have been commissioned and started synchronous daily observations of IPS of a few compact radio sources with relative time accuracy of about ± 1 millisec. The third telescope at Surat is expected to go in operation by the end of 1983. As soon as all the three telescopes go in for simultaneous operation, it is proposed to (1) augment the telescope sensitivity so as to detect sources with flux density ~ 1 Jansky (2) incorporate better time and frequency standards at each station which can be synchronised to better than μs relative time accuracy (3) develop suitable receivers and data acquisition system for generating interference fringes using a general purpose computer and (4) take advantage of the availability of three telescopes to incorporate ‘closure phase and amplitude’ techniques which eliminate undesirable atmospheric and ionospheric phase distortions.
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 describe our experience and provide guidelines for maximum safe balloon sizes according to age in children undergoing balloon dilatation.
A retrospective review was conducted of children undergoing balloon dilatation for subglottic stenosis in a paediatric tertiary unit between May 2006 and February 2016.
A total of 166 patients underwent balloon dilatation. Mean ( ± standard deviation) patient age was 4.5 ± 3.99 years. The median balloon size was 8 mm, the median balloon inflation pressure was 10 atm, and the mean balloon inflation time was 65.1 ± 18.6 seconds. No significant unexpected events occurred. The Pearson correlation co-efficient for the relationship between patient age and balloon size was 0.85 (p = 0.001), suggesting a strongly positive correlation.
This study demonstrated that balloon dilatation is a safe procedure for airway stenosis. The results suggest using a balloon diameter that is equal to the outer diameter of the age-appropriate endotracheal tube +1 mm for the larynx and subglottis and +2 mm for the trachea.
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.
The State of Qatar experienced a sandstorm on the night of April 1, 2015, lasting approximately 12 hours, with winds of more than 100 km/h and average particulate matter of approximately 10 μm in diameter. The emergency department (ED) of the main tertiary hospital in Qatar managed 62% of the total emergency calls and those of higher triage order. The peak load of patients during the event manifested approximately 6 hours after the onset. The Major Emergency Command Centre of the hospital ensured the department was maximally organized in terms of disaster management, and established protocols were brought into action. Multiple timely meetings were convened in efforts to effectively execute plans that included rapid emergency medical services handover time, resourcing staff, maximizing bed space, preventing dust entry in the ED, bypassing certain administrative processes, canceling day-surgeries that did not affect inpatient morbidity, and procuring additional respiratory equipment. Patients arrived mainly with exacerbations of asthma and respiratory distress, ophthalmic emergencies, and vehicular trauma; surprisingly, the incidence of pedestrian injuries did not vary. (Disaster Med Public Health Preparedness. 2017;11:227–238)
This study aimed to assess the utility of onlay pectoralis major myofascial flap in preventing pharyngocutaneous fistula following salvage total laryngectomy.
A retrospective analysis was performed of 172 patients who underwent salvage laryngectomy for recurrent carcinoma of the larynx or hypopharynx between 1999 and 2014. One hundred and ten patients underwent primary closure and 62 patients had pectoralis major myofascial flap onlay.
The overall pharyngocutaneous fistula rate was 43 per cent, and was similar in both groups (primary closure group, 43.6 per cent; onlay flap group, 41.9 per cent; p = 0.8). Fistulae in the onlay flap group healed faster: the median and mean fistula duration were 37 and 55 days, respectively, in the primary closure group and 20 and 25 days, respectively, in the onlay flap group (p = 0.008).
Use of an onlay pectoralis major myofascial flap did not decrease the pharyngocutaneous fistula rate, although fistula duration was shortened. A well-designed randomised-controlled trial is needed to establish parameters for its routine use in clinical practice.
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.
To investigate the assessment and management of paediatric snoring and obstructive sleep apnoea in UK otolaryngology departments.
A telephone questionnaire survey of UK otolaryngology departments was conducted over a 16-week period.
The response rate was 61 per cent (85 out of 139 trusts). Use of pre-operative pulse oximetry was reported by 84 per cent of respondents, mainly to diagnose obstructive sleep apnoea (73 per cent) or stratify post-operative risk (46 per cent). Thirty-one per cent of respondents reported using post-operative pulse oximetry. Twenty-five per cent of respondents have a dedicated management protocol for paediatric obstructive sleep apnoea and snoring. Thirty-four per cent require prior clinical commissioning group approval before performing surgery. Fifty-eight per cent of respondents reported following up their obstructive sleep apnoea patients after surgery. The mean follow-up period (±standard deviation) was 6.8 ± 1.2 weeks.
There is variation in the assessment and management of paediatric snoring and obstructive sleep apnoea across the UK, particularly in the use of pre- and post-operative pulse oximetry monitoring, and further guidelines regarding this are necessary.
To assess the efficacy of endoscopic-guided botulinum toxin injection into the cricopharyngeus muscle and evaluate the duration of its effects.
A 3-year prospective study of 12 patients undergoing injection of botulinum toxin was conducted, with a telephone survey to assess dysphagia pre-operatively, and at 1, 3 and 6 months post-treatment, using the MD Anderson Dysphagia Inventory.
Median age was 66.2 years. Causes of cricopharyngeal dysphagia included idiopathic cricopharyngeal hypertrophy (67 per cent), previous cerebrovascular accident (17 per cent), cranial nerve palsy (8 per cent) and previous chemoradiotherapy to the neck (8 per cent). There were no complications. Two patients had repeat injections after six months. There was significant improvement in MD Anderson Dysphagia Inventory scores at one and three months versus pre-operative scores (73.1 ± 14.9 vs 46.9 ± 7.6, p = 0.0001, and 65.1 ± 11.5 vs 46.9 ± 7.6, p = 0.0001), but not at six months (51.0 ± 11.0 vs 46.9 ± 7.6, p = 0.14).
Endoscopic-guided injection of botulinum toxin into the cricopharyngeus muscle is a safe and effective method for treating cricopharyngeal muscle dysfunction, lasting up to six months.
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.
Although type 2 respiratory failure is a plausible late presentation for laryngeal tumours, very little published literature is available to support this theory.
This paper describes the unusual presentation of a subglottic tumour with uncompensated type 2 respiratory failure.
The patient was initially managed with biphasic positive airway pressure as a bridging measure while awaiting intensive care treatment and to provide sufficient time to arrange a surgical tracheostomy.
This case highlights the importance of clinical suspicion towards subglottic tumours in patients presenting with type 2 respiratory failure. The positive outcome indicates that biphasic positive airway pressure is a potential bridging therapy for upper airway obstruction and a safe and stable treatment option for patients in respiratory distress.
To assess the benefits of frenotomy on breastfeeding in infants, and determine the influence of age.
A telephone questionnaire of all patients diagnosed with tongue-tie over 12 months was conducted pre-intervention and 1-month post-intervention. The Infant Breastfeeding Assessment Tool was used to assess breastfeeding.
Of 54 infants diagnosed with tongue-tie, 78 per cent of mothers participated in the survey. Eighty-six per cent of patients underwent frenotomy, with no surgical complications. In the frenotomy group, 81 per cent of mothers reported improvement in breastfeeding, versus 17 per cent in the non-surgical group (p = 0.0074). In the frenotomy group, the mean (±standard deviation) Infant Breastfeeding Assessment Tool score was 3.33 ± 1.51 pre-intervention, versus 9.19 ± 2.44 post-intervention (p = 0.0001). In the non-surgical intervention group, the mean score (±standard deviation) was 4.17 ± 0.75 pre-intervention, versus 6.00 ± 1.73 post-intervention (p = 0.16). For infants who underwent frenotomy, there was a reported improvement in 94 per cent of those aged less than 30 days, versus 68 per cent in infants aged over 30 days (p = 0.092).
Frenotomy is a safe, short procedure that improves breastfeeding outcomes, and is best performed at an early age.