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Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) refractory to conventional therapy can lead to marked disability and represents a therapeutic challenge.
To report five cases of treatment-refractory disabling CIDP treated with autologous hematopoietic stem cell transplantation (AHSCT).
This was a retrospective cohort study from a tertiary care referral center for both neuromuscular disease and AHSCT. Patients with CIDP treated with AHSCT between 2008 and 2020 were included. All patients had major persistent and disabling neuropathic deficits despite combinations of intensive immunosuppressive therapy. The primary outcome measures were: Medical Research Council sum score, Overall Neuropathy Limitations Scale and requirement for ongoing CIDP immunotherapy after transplantation. We also analyzed safety outcomes by documenting all severe AHSCT-related complications.
Five patients with refractory CIDP underwent AHSCT. Three were classified as manifesting a typical syndrome, two were classified as the multifocal Lewis Sumner variant. The mean age at time of CIDP diagnosis was 33.4 years (range 24–46 years), with a median delay of 46 months (range 21–135 months) between diagnosis and AHSCT. The median follow-up period was 41 months. All five patients were able to wean off CIDP-related immunotherapy. Marked improvements in Medical Research Council scale and overall Neuropathy Limitations Scale were noted in 4/5 patients. One patient with longstanding neurogenic atrophy showed no improvement in disability scales. There were no treatment-related deaths or critical illnesses.
AHSCT can achieve marked sustained clinical improvement of refractory CIDP and may allow for weaning off long-term complex immunotherapies.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments.
A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost–benefit ratio and new perspectives on the potential for green growth in the short- and long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations.
Social media summary
Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
Guinea grass (Megathyrsus maximus Jacq.) is an important forage species in vast rangelands/grasslands of India and several tropical countries owing to its high biomass yield, good nutritional quality and wide adaptation. Evaluation of the existing natural variation and selection of desirable genotypes is the most plausible breeding method for this apomictic and polyploid grass. Developing a core sub-set to narrow down the number of germplasm required for future genetic studies is also pertinent. The present study involved characterization of 152 diverse M. maximus germplasm representing collections from different agro-ecological zones of India as well as those procured from Africa and Brazil; and development of a core sub-set. Nineteen metric, seven non-metric and nine nutritive traits together established the presence of wide variability among the genotypes. Clustering of the genotypes resulted in eight distinct clusters. The largest cluster included genotypes from Ethiopia, north India, north-western India, south India and north-eastern hill region, thus represented the highest diversity. Eleven of the total 26 Ethiopian genotypes clustered together. Non-metric morphological traits effectively differentiated the genotypes, and were associated with nutritional quality also. Genotypes which flowered once in a year showed slightly better crude protein and digestibility. The clusters were further sub-clustered and representatives were selected to develop the core sub-set of 23 genotypes comprising 20 indigenous and three exotic accessions. Comparison of the range of diversity and mean value for traits as obtained in the core sub-set and that in the total germplasm indicated successful capturing of maximum diversity in the core sub-set.
Stress associated with caring for a mentally ill spouse can adversely affect the health status of caregivers and their children. Adding to the stress of caregiving is the stigma often placed against spouses and children of people with mental illness. Contrary to mental illness, many physical disorders such as cancer may be less stigmatized (expect pulmonary cancer). In this study, we measured externalized and internalized stigma, as well as psychological (depressive symptoms and stressful life events) and physiological (basal salivary cortisol levels) markers of stress in 115 spouses and 154 children of parents suffering from major depressive disorder, cancer, or no illness (control group). The results show that spouses and children from families with parental depression present significantly more externalized stigma than spouses and children from families with parental cancer or no illness, although we find no group differences on internalized stigma. The analysis did not show a significant group difference either for spouses or their children on depressive symptomatology, although spouses from the parental depression group reported greater work/family stress. Finally, we found that although for both spouses children the awakening cortisol response was greater on weekdays than on weekend days, salivary cortisol levels did not differ between groups. Bayes factor calculated on the null result for cortisol levels was greater than 100, providing strong evidence for the null hypothesis H0. Altogether, these results suggest an impact of stigma toward mental health disorder on psychological markers of stress but no impact of stigma on physiological markers of stress. We suggest that these results may be due to the characteristics of the families who participated in the present study.
Ductal stents, right ventricular outflow tract stents, and aortopulmonary shunts are used to palliate newborns and infants with reduced pulmonary blood flow. Current long-term outcomes of these palliations from resource-restricted countries are unknown.
This single-centre, retrospective, observational study analysed the technical success, immediate and late mortality, re-interventions, and length of palliation in infants ≤5 kg who underwent aortopulmonary shunts, ductal, and pulmonary outflow stents. Patients were grouped by their anatomy.
There were 69 infants who underwent one of the palliations. Technical success was 90% for aortopulmonary shunts (n = 10), 91% for pulmonary outflow stents (n = 11) and 100% for ductal stents (n = 48). Early mortality within 30 days in 12/69 patients was observed in 20% after shunts, 9% after pulmonary outflow stents, and 19% after ductal stents. Late mortality in 11 patients was seen in 20% after shunts, 18% after outflow stents, and 15% after ductal stents. Seven patients needed re-interventions; two following shunts, one following outflow stent, and four following ductal stents for hypoxia. Among the anatomical groups, 10/12 patients with pulmonary atresia, intact ventricular septum survived after valvotomy and ductal stenting. Survival to Glenn shunt after ductal stent for pulmonary atresia, intact ventricular septum and diminutive right ventricle was very low in two out of eight patients, but very good (100%) for other univentricular hearts. Among 35 patients with biventricular lesions, 22 survived to the next stage.
Cyanotic infants, despite undergoing technically successful palliation had a high inter-stage mortality irrespective of the type of palliation. Duct stenting in univentricular hearts and in pulmonary atresia with an intact ventricular septum and adequate sized right ventricle tended to have low mortality and better long-term outcome. Completion of biventricular repair after palliation was achieved only in 63% of patients, reflecting unique challenges in developing countries despite advances in intensive care and interventions.
Reward Deficiency Syndrome (RDS) is an umbrella term for all drug and nondrug addictive behaviors, due to a dopamine deficiency, “hypodopaminergia.” There is an opioid-overdose epidemic in the USA, which may result in or worsen RDS. A paradigm shift is needed to combat a system that is not working. This shift involves the recognition of dopamine homeostasis as the ultimate treatment of RDS via precision, genetically guided KB220 variants, called Precision Behavioral Management (PBM). Recognition of RDS as an endophenotype and an umbrella term in the future DSM 6, following the Research Domain Criteria (RDoC), would assist in shifting this paradigm.
Prolonged survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on environmental surfaces and personal protective equipment may lead to these surfaces transmitting this pathogen to others. We sought to determine the effectiveness of a pulsed-xenon ultraviolet (PX-UV) disinfection system in reducing the load of SARS-CoV-2 on hard surfaces and N95 respirators.
Chamber slides and N95 respirator material were directly inoculated with SARS-CoV-2 and were exposed to different durations of PX-UV.
For hard surfaces, disinfection for 1, 2, and 5 minutes resulted in 3.53 log10, >4.54 log10, and >4.12 log10 reductions in viral load, respectively. For N95 respirators, disinfection for 5 minutes resulted in >4.79 log10 reduction in viral load. PX-UV significantly reduced SARS-CoV-2 on hard surfaces and N95 respirators.
With the potential to rapidly disinfectant environmental surfaces and N95 respirators, PX-UV devices are a promising technology to reduce environmental and personal protective equipment bioburden and to enhance both healthcare worker and patient safety by reducing the risk of exposure to SARS-CoV-2.
Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
The Hawkesbury Sandstone (Hawkesbury Series, Sydney Basin) on the southeastern coast of New South Wales, Australia, preserves a depauperate but important vertebrate tetrapod body-fossil record from the Early and Middle Triassic. As with many fossil sites around the world, the ichnological record has helped to shed light on the paleoecology of this interval. Herein, we investigate historical reports of a trackway pertaining to a putative short-tailed reptile found at Berowra Creek in the 1940s. Reinvestigation of the surviving track-bearing slabs augmented by archival photographs of the complete trackway, suggests that these impressions, which consist primarily of didactyl tracks (plus less common monodactyl and tridactyl traces), represent the earliest example of a swimming tetrapod found in Australia. Another isolated specimen (possibly from a nearby locality at Annangrove) appears to represent similar didactyl swim traces of a second, larger individual. Although the identities of the trackmakers are unknown, the Berowra Creek individual had an estimated body length of between ~80 cm (short-coupled) and 1.35 m (long-coupled), and produced the subaqueous trackway while travelling upslope (against the current) on a sandbar within a braided river system of the Hawkesbury Sandstone. These trackways partially resemble amphibian swim traces in the so-called Batrachichnus C Lunichnium continuum, but appear to represent a unique locomotion trace. This reanalysis of the Berowra Creek trackway provides insight into the locomotion of tetrapods of the Triassic Hawkesbury Series, which remains a poorly understood aspect of their life history.
Background: Telemedicine has been defined as the use of technology to provide healthcare when the provider and patient are geographically separated. Use of telemedicine to meet the needs of specific populations has become increasingly common across Canada. The current study employs the Ontario Telemedicine Network (OTN) to connect the emergency departments of a community hospital system and a pediatric tertiary care hospital. OTN functions through a two-way video conferencing system, allowing physicians at the tertiary site to see and hear the patient being treated in the community hospitals. Aim Statement: The aim of this project is to ensure essential care is provided to CTAS 1 and 2 pediatric patients who present to Niagara Health emergency departments, to increase the number of appropriate patient transfers. Measures & Design: Data for this project include a) description of common diagnoses, b) time of call, c) occurrence of transfers, and d) professional perceptions of the technology. A descriptive design was used together with the implementation of quality improvement cycles as the intervention occurred. Quality improvement methodologies including plan-do-study-act (PDSA) cycles ensured continuous improvement to the process of OTN use and therefore patient safety throughout the study. Evaluation/Results: Since the intervention was employed on December 17, 2018 there have been a total of 19 cases for which 4 transfers were requested. Changes to the process were made including the addition of weekly technology tests and feedback to health professionals involved to garner further support for the use. Results have indicated that seizure was the most common diagnosis, accounting for 37% of cases. The majority of calls were placed after 19:00 hours with no calls being placed between 24:00 and 10:00. Discussion/Impact: Healthcare providers had positive perceptions of the technology agreeing that decision making between on-site and remote teams was timely and collaborative, as well as that patient care and outcomes were improved with its use. The results of this study will be used to determine the benefits of employing telemedicine in the emergency departments of other hospital systems.
The combination of clozapine and other potentially leukopenic drugs may pose a greater risk for neutropenia. However, neutropenia may not always be due to clozapine. When adding potentially leukopenic drugs, clinicians should look for possible alternatives especially as clozapine is often a drug used as the last resort in treatment refractory schizophrenia.
Topiramate is an antiepileptic agent, which is being investigated as a mood-stabilizer. Three obese individuals with DSM-IV bipolar I disorder and type II diabetes mellitus received topiramate treatment in combination with antipsychotics and valproate or carbamazepine. In addition to improved mood stability, these individuals lost between 16 to 20.5% of their pre-topiramate body weight and also achieved significant glycemic control.
“Folie à deux” is also known in the ICD-10 as Induced Delusional Disorder. A subtype is “folie imposee” where the primary individual holds delusional beliefs shared by a secondary individual. When the delusional beliefs of the primary individual cease it is observed that the beliefs of the secondary individual also disappear. Mr A was a 36 year old Caucasian male presenting with an array of psychotic symptoms centred on a task which involved finding an energy source at the centre of the earth. Mrs A was highly resistant to his treatment and further investigation revealed a case of folie à deux.
To demonstrate the phenomenon of folie à deux.
Individual and combined interviews were held with Mr and Mrs A where the psychotic symptoms were discussed. A comprehensive study of Mr A's past and current psychopathology was also undertaken.
Mrs A shared the delusions of her partner and was strongly against treatment as it would nullify his delusions rendering him incapable of completing his task. Once treatment was facilitated, Mr A experienced a drop from his unusually high levels of energy which reflected an equal and immediate drop in energy levels of his partner which led her to further discourage him from medication. When Mr A's delusional beliefs lifted, it was apparent that his partner no longer held the same delusional beliefs.
We concluded this case fulfilled ICD-10 and DSM IV criteria for a shared delusional disorder (folie à deux) with specific sub-type “folie imposee”.
Constituting 2% of the population, PWDID are a vulnerable group with a higher prevalence of mental disorders than the general population. ICD diagnostic criteria often rely on adequate cognitive functioning and hence diagnosis of mental disorders in PWDID can be difficult, consequently leading to inequity of treatment, prognosis and stigma. Our study critically analysed the available evidence base and explored the feasibility of applying modified diagnostic criteria within the context of cumulative iterative iteration. We present the outcome using diagnosis of DID and anxiety disorder as examples.
Address current shortcomings in ICD classification regarding PWDID by contributing effectively to the WHO ICD-11 consultation process in collaboration with international stakeholders.
Facilitate accessibility of ICD-11 criteria for diagnosis of mental disorders capable of engendering robust evidence based epidemiological data and healthcare in PWDID.
We evaluated current evidence via a systematic literature search utilising PRISMA guidelines and developed pragmatic guidelines to adapt ICD diagnostic criteria in PWDID. A brief screener [Glasgow Level of Ability and Development Scale (GLADs)] for detecting DID was also studied internationally within the context of clinical utility (n = 136).
The evidence base relating to mental disorders in PWDID is poor, significantly hampered by difficulties in applicability of diagnostic criteria. The GLADs appears to be a promising screening tool with good clinical utility for detecting disorders of intellectual development (DID) particularly where resources are scarce.
Pragmatic modifications to ICD-11 diagnostic criteria and the GLADS tool facilitates its clinical utility for PWDID and contributes significantly to enhancing research based evidence, and, ultimately their health access and well-being.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
Silicon carbide (SiC) is ideally suitable as a sensor material in harsh environments. Despite the brittleness in the macroscopic scale, plasticity in SiC is observed at small component length-scales. Previous nanoindentation based study combining experiment and numerical approaches of single-crystal 6H-SiC has shown that slip activation is rather complex, and that non-basal slip could potentially dominate the plastic deformation behaviour. In this study, we investigated the local deformation response evolution of shear strain directly under and in the vicinity of the indenter tip. The results show the pyramidal slip families contribute significantly to the deformation process.
We identify mechanisms through which open-loop control of thermoacoustic instability is achieved in a laminar combustor and characterize them using synchronization theory. The thermoacoustic system comprises two nonlinearly coupled damped harmonic oscillators – acoustic and unsteady heat release rate (HRR) field – each possessing different eigenfrequencies. The frequency of the preferred mode of HRR oscillations is less than the third acoustic eigenfrequency where thermoacoustic instability develops. We systematically subject the limit-cycle oscillations to an external harmonic forcing at different frequencies and amplitudes. We observe that forcing at a frequency near the preferred mode of the HRR oscillator leads to a greater than 90 % decrease in the amplitude of the limit-cycle oscillations through the phenomenon of asynchronous quenching. Concurrently, there is a resonant amplification in the amplitude of HRR oscillations. Further, we show that the flame dynamics plays a key role in controlling the frequency at which quenching is observed. Most importantly, we show that forcing can cause asynchronous quenching either by imposing out-of-phase relation between pressure and HRR oscillations or by inducing period-2 dynamics in pressure oscillations while period-1 in HRR oscillations, thereby causing phase drifting between the two subsystems. In each of the two cases, acoustic driving is very low and hence thermoacoustic instability is suppressed. We show that the characteristics of forced synchronization of the pressure and HRR oscillations are significantly different. Thus, we find that the simultaneous characterization of the two subsystems is necessary to quantify completely the nonlinear response of the forced thermoacoustic system.
Population Decline in New Ireland, Papua New Guinea
In this chapter I discuss my own research and clinical experiences in Papua New Guinea, where I worked between 1947 and 1974 and had subsequent visits up until 1987, studying the relationship between community infertility and the prevalence of gonorrhea. Its particular significance for this volume is that this was the first time that a rigorous and systematic clinical and medical examination had been performed on a population suffering from widespread infertility to determine whether psychosocial factors or STIs—and specifically gonorrhea—were the source of the community's infertility. Gonorrhea was, indeed, found to be the cause in the Tabar Islands, and the hypothesis was confirmed by a concurrent program of universal penicillin distribution throughout the Tabar population resulting in a remarkable rebound in fertility and a reversal of the population decline.
I was born in New Zealand, and through to my graduation in medicine had regular contact with Pacific Islanders and missionaries. However, my engagement with New Guinea research began by chance. Medical interns without a family medical background were and are influenced by the role models presented by their teachers. My future career was subtly influenced by Sir John Cleland, professor of pathology, who had studied and written extensively on anthropology and Australian Aboriginal health. He offered me a medical research position in Arnhem Land, but I saw medical positions available in the Territory of Papua and New Guinea. In August 1947 I became the thirteenth medical officer to be appointed after World War II, to a country where the fortunate were receiving medical care from barefoot orderlies, but many others had no medical contact.
There were no numerators or denominators to measure the impact of endemic and introduced diseases on the inhabitants of this tropical environment. In 1948, as medical officer at Sohano on Buka Island, a large island just north of Bougainville Island, I set about establishing medical records and genealogies of two Buka communities: Lemankoa, a large village of the Haku tribe on the northwest coast; and villages of the inland Solas people along the Gagan River. I had access to the birth, death, and marriage records collected by Catholic missionaries since 1915, which were preserved in bound volumes that had been wrapped in banana leaves and hidden in caves during the war.