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Background: Adverse effects and risks associated with glucocorticoid (GC) treatment are frequently encountered in immune-mediated neuromuscular disorders. However, significant variability exists in the management of these complications. Our aim was to establish international consensus guidance on the management of GC-related complications in neuromuscular disorders. Methods: An international task force of 15 experts was assembled to develop clinical recommendations for managing GC-related complications in neuromuscular patients. The RAND/UCLA Appropriateness Method (RAM) was employed to formulate consensus guidance statements. Initial statements were drafted following a comprehensive literature review and were refined based on anonymous expert feedback, with up to three rounds of email voting to achieve consensus. Results: Consensus was reached on statements addressing general patient care, monitoring during GC therapy, osteoporosis prevention, vaccinations, infection screening, and prophylaxis for Pneumocystis jiroveci pneumonia. A multidisciplinary approach to managing GC-related complications was highlighted as a key recommendation. Conclusions: This represents the first consensus guidance in the neurological literature on GC complications, and offer clinicians structured guidance on mitigating and managing common adverse effects associated with both short- and long-term GC use. They also provide a foundation for future debate, quality improvement, research work in this area.
We provide an assessment of the Infinity Two fusion pilot plant (FPP) baseline plasma physics design. Infinity Two is a four-field period, aspect ratio $A = 10$, quasi-isodynamic stellarator with improved confinement appealing to a max-$J$ approach, elevated plasma density and high magnetic fields ($ \langle B\rangle = 9$ T). Here $J$ denotes the second adiabatic invariant. At the envisioned operating point ($800$ MW deuterium-tritium (DT) fusion), the configuration has robust magnetic surfaces based on magnetohydrodynamic (MHD) equilibrium calculations and is stable to both local and global MHD instabilities. The configuration has excellent confinement properties with small neoclassical transport and low bootstrap current ($|I_{bootstrap}| \sim 2$ kA). Calculations of collisional alpha-particle confinement in a DT FPP scenario show small energy losses to the first wall (${\lt}1.5 \,\%$) and stable energetic particle/Alfvén eigenmodes at high ion density. Low turbulent transport is produced using a combination of density profile control consistent with pellet fueling and reduced stiffness to turbulent transport via three-dimensional shaping. Transport simulations with the T3D-GX-SFINCS code suite with self-consistent turbulent and neoclassical transport predict that the DT fusion power$P_{{fus}}=800$ MW operating point is attainable with high fusion gain ($Q=40$) at volume-averaged electron densities $n_e\approx 2 \times 10^{20}$ m$^{-3}$, below the Sudo density limit. Additional transport calculations show that an ignited ($Q=\infty$) solution is available at slightly higher density ($2.2 \times 10^{20}$ m$^{-3}$) with $P_{{fus}}=1.5$ GW. The magnetic configuration is defined by a magnetic coil set with sufficient room for an island divertor, shielding and blanket solutions with tritium breeding ratios (TBR) above unity. An optimistic estimate for the gas-cooled solid breeder designed helium-cooled pebble bed is TBR $\sim 1.3$. Infinity Two satisfies the physics requirements of a stellarator fusion pilot plant.
In this work, we present a detailed assessment of fusion-born alpha-particle confinement, their wall loads and stability of Alfvén eigenmodes driven by these energetic particles in the Infinity Two Fusion Pilot Plant baseline plasma design, a four-field-period quasi-isodynamic stellarator to operate in deuterium–tritium fusion conditions. Using the Monte Carlo codes, SIMPLE, ASCOT5 and KORC-T, we study the collisionless and collisional dynamics of guiding-centre and full-orbit alpha-particles in the core plasma. We find that core energy losses to the wall are less than 4 %. Our simulations shows that peak power loads on the wall of this configuration are approximately 2.5 MW m-$^2$ and are spatially localised, toroidally and poloidaly, in the vicinity of x-points of the magnetic island chain $n/m = 4/5$ outside the plasma volume. Also, an exploratory analysis using various simplified walls shows that shaping and distance of the wall from the plasma volume can help reduce peak power loads. Our stability assessment of Alfvén eigenmodes using the STELLGAP and FAR3d codes shows the absence of unstable modes driven by alpha-particles in Infinity Two due to the relatively low alpha-particle beta at the envisioned 800 MW operating scenario.
An analysis of the divertor designs for the Infinity Two fusion pilot plant (FPP) baseline plasma design is presented. The divertor uses an $m=5$, $n=4$ magnetic island chain, where m is the poloidal number and n is the toroidal number. Two divertor designs are presented. A classical divertor that is similar to the Wendelstein 7-X island divertor is analyzed using diffusive field-line following and the fluid code EMC3-Lite. For a baseline $800\text{ MW}$ operating point in Infinity Two, the conditions where the heat flux on the divertor plate remains in the acceptable region are analyzed. In addition a related, but different and novel large island backside divertor (LIBD) design is shown. The LIBD promises improved neutral pumping by closing the divertor through the use of baffling and with a structure inside the island, thus preventing neutralized plasma particles from reente ring the plasma.
The magnetohydrodynamic (MHD) equilibrium and stability properties of the Infinity Two fusion pilot plant baseline plasma physics design are presented. The configuration is a four-field period, aspect ratio $A = 10$ quasi-isodynamic stellarator optimised for excellent confinement at elevated density and high magnetic field $B = 9\,T$. Magnetic surfaces exist in the plasma core in vacuum and retain good equilibrium surface integrity from vacuum to an operational $\beta = 1.6 \,\%$, the ratio of the volume average of the plasma and magnetic pressures, corresponding to $800\ \textrm{MW}$ deuterium–tritium fusion operation. Neoclassical calculations show that a self-consistent bootstrap current of the order of ${\sim} 1\ \textrm{kA}$ slightly increases the rotational transform profile by less than 0.001. The configuration has a magnetic well across its entire radius. From vacuum to the operating point, the configuration exhibits good ballooning stability characteristics, exhibits good Mercier stability across most of its minor radius and it is stable against global low-n MHD instabilities up to $\beta = 3.2\,\%$.
This study aimed to characterise the ipsilateral, contralateral and bilateral masseter vestibular-evoked myogenic potential using clicks and 500 Hz tone burst stimuli in healthy adults.
Method
Masseter vestibular-evoked myogenic potential was recorded from 20 healthy participants aged 19–28 years (11 males and 9 females). Masseter vestibular-evoked myogenic potential was recorded using 500 Hz tone burst and click stimuli in ipsilateral, contralateral and bilateral modes.
Results
A statistically significant difference was observed between ipsilateral and contralateral stimulation for p11 latency, n21 latency and p11-n21 amplitude for both click and 500 Hz tone burst stimuli. The amplitude of the p11-n21 complex was higher for ipsilateral, contralateral and bilateral stimulations for 500 Hz tone burst than for click stimulus.
Conclusion
This study showed a significant difference for p11-n21 amplitude between click and 500 Hz tone burst evoked masseter vestibular-evoked myogenic potential. In addition, bilateral stimulation elicited a larger response than ipsilateral and contralateral stimulation.
Trichotillomania (TTM), also known as hair pulling disorder, is an obsessive- compulsive disorder characterized by the recurrent, overwhelming urge to repeatedly pull out one’s hair. Hair pulling can occur anywhere on the body but is most common on the scalp, eyebrows, and eyelashes and subsequently results in bald patches. While TTM is a very prevalent, debilitating disorder, there is still no FDA approved treatment that exists.
Objectives
The main objective of this study is to explore the various forms of available psychotherapy available for the treatment of trichotillomania.
Methods
Two independent reviewers conducted title, abstract, full-text searching and data extraction among the PubMed, PsycINFO, and ResearchGate data bases. Of the 79 articles screened, five were included in this review
Results
Habit reversal therapy (HRT) is a form of cognitive behavioral therapy that is considered the first line treatment for management of TTM. Other psychotherapeutic techniques include acceptance and commitment therapy, progressive muscle relaxation, and mindfulness therapy.
Conclusions
This study supports the current data which states that HRT is the first line treatment and there is yet to be a pharmacological treatment of choice for TTM. It is also very important to note that TTM is still underdiagnosed and can be mistaken for a dermatological disorder like alopecia aerata. Furthermore, many people with trichilemmoma have underlying mental health disorders such as anxiety and depression that must first be addressed before treating the hair pulling itself.
Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of coronavirus disease 2019 (COVID-19) in a large male prison in Wales, UK, October 2020 to April 2021, and discuss control measures.
We gathered case-information, including demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole-genome sequencing (WGS) and interviews determined the genetic relationship between cases plausibility of transmission.
Of 453 cases, 53% (n = 242) were staff, most aged 25–34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95% CI 26–64%) than in residents (12%, 95% CI 9–15%).
Whole-genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualisation, allowed dynamic risk assessment and proportionate control measures, minimising the reduction in resident welfare.
Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society. Key observations and findings include:
– high escape rates of early Mars' atmosphere, including loss of water, impact present-day habitability;
– putative fossils on Mars will likely be ambiguous biomarkers for life;
– microbial contamination resulting from human habitation is unavoidable; and
– based on Mars' current planetary protection category, robotic payload(s) should characterize the local martian environment for any life-forms prior to human habitation.
Some of the outstanding questions are:
– which interpretation of the hemispheric dichotomy of the planet is correct;
– to what degree did deep-penetrating faults transport subsurface liquids to Mars' surface;
– in what abundance are carbonates formed by atmospheric processes;
– what properties of martian meteorites could be used to constrain their source locations;
– the origin(s) of organic macromolecules;
– was/is Mars inhabited;
– how can missions designed to uncover microbial activity in the subsurface eliminate potential false positives caused by microbial contaminants from Earth;
– how can we ensure that humans and microbes form a stable and benign biosphere; and
– should humans relate to putative extraterrestrial life from a biocentric viewpoint (preservation of all biology), or anthropocentric viewpoint of expanding habitation of space?
Studies of Mars' evolution can shed light on the habitability of extrasolar planets. In addition, Mars exploration can drive future policy developments and confirm (or put into question) the feasibility and/or extent of human habitability of space.
Five species of Eremothecella are recorded from the Andaman Islands, two of which are described as new: Eremothecella ajaysinghii Jagad. Ram & G. P. Sinha and E. nicobarica Jagad. Ram & G. P. Sinha. Eremothecella ajaysinghii has whitish grey, pruinose ascomata and 8–10(–11)-septate ascospores, while E. nicobarica has non-pruinose ascomata and (14–)15–17-septate ascospores. Eremothecella calamicola Syd., E. macrosperma (Zahlbr.) Sérus. and E. variratae (Aptroot & Sipman) Sérus. are reported as new records for India. An updated worldwide key to species of the genus is presented.
The present work aims to explore the mechanism of action of C-cinnamoyl glycoside as an antifilarial agent against the bovine filarial nematode Setaria cervi. Both apoptosis and autophagy programmed cell death pathways play a significant role in parasitic death. The generation of reactive oxygen species, alteration of the level of antioxidant components and disruption of mitochondrial membrane potential may be the causative factors that drive the parasitic death. Monitoring of autophagic flux via the formation of autophagosome and autophagolysosome was detected via CYTO ID dye. The expression profiling of both apoptotic and autophagic marker proteins strongly support the initial findings of these two cell death processes. The increased interaction of pro-autophagic protein Beclin1 with BCL-2 may promote apoptotic pathway by suppressing anti-apoptotic protein BCL-2 from its function. This in turn partially restrains the autophagic pathway by engaging Beclin1 in the complex. But overall positive increment in autophagic flux was observed. Dynamic interaction and regulative balance of these two critical cellular pathways play a decisive role in controlling disease pathogenesis. Therefore, the present experimental work may prosper the chance for C-cinnamoyl glycosides to become a potential antifilarial therapeutic in the upcoming day after detail in vivo study and proper clinical trial.
Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β. This immune polarization was also evidenced by upregulation of nuclear factor-κ light-chain enhancer of activated B cells p50 and regulated expression of suppressor of mother against decapentaplegic protein-4. rLd-iPGAM stimulation also promoted lymphocyte proliferation and boosted the leishmaniacidal activity of macrophages by upregulating reactive oxygen species. It also induced 1·8-fold higher release of nitric oxide (NO) by promoting the transcription of inducible nitric oxide synthase gene. Besides, in silico analysis suggested the presence of major histocompatibility complex class I and II restricted epitopes, which can proficiently trigger CD8+ and CD4+ cells, respectively. This study reports rLd-iPGAM as an effective immunoprophylactic agent, which can be used in future vaccine design.
It is known that in the radio spertrum the limb of the quiet sun is brighter in the equatorial regions than near the pole. But most of the available theoretical calculations of the brightness distribution over the quiet sun have been made with the assumption of spherical symmetry. We have therefore calculated two-dimensional distributions at several decimetre and metre wavelengths, taking account of the observed asymmetry in the north-south direction. Newkirk’s method of ray-tracing was used, the calculations being made with a CDC 3600 computer. Some of the preliminary results (particularly for a sunspot minimum period) are presented here; they indicate that the electron temperature of the solar corona has a value of about 1 to 1.5 x 106 °K.
A systematic review of the literature was conducted to identify effective approaches to preventing and addressing abuse and neglect of older adults within health care settings in Canada. The review was conducted using databases searched from January 2000–April-May 2013. Additionally, expert panel members submitted article citations from personal archives. Two research associates (NRA) screened each title and abstract for inclusion. After inter-rater reliability was determined between the NRAs (Kappa score of 0.76), the records were divided, appraised, and data extracted independently. The review resulted in 62 studies that focused on identifying, assessing, and responding to abuse and neglect of older adults; education, prevention, and health promotion strategies; and organizational and system-level supports to prevent and respond to abuse and neglect. Abuse and neglect of older adults remains under-explored in terms of evidence-based studies; consequently, further research in all of the areas described in the results is needed.
Head and face dimensions vary according to race and geographical zone. Hereditary factors also greatly affect the size and shape of the head. There are important medical applications of craniofacial data specific to different racial and ethnic groups.
Methods:
Various cranial and facial anthropometric parameters were assessed in singleton, healthy, full-term newborns of Sikkimese origin in a tertiary care hospital in Sikkim, India. The data were then analysed to determine statistically significant differences between sexes.
Results:
Forty-five newborns were included in the study. Both male and female newborns were observed to be hyperbrachycephalic and hyperleptoprosopic. The only significant difference between the sexes was in commissural length, which was observed to be greater in male newborns.
Conclusion:
Craniofacial parameters in Sikkimese newborns vary in comparison with those of other newborns from around the world. Larger studies are needed in order to reveal sex-related variations. Similar studies on various racial groups in North-East India are needed to establish standards for populations with East Asian features.
Executive functioning is widely targeted when human cognition is assessed, but there is little consensus on how it should be operationalized and measured. Recognizing the difficulties associated with establishing standard operational definitions of executive functioning, the National Institute of Neurological Disorders and Stroke entered into a contract with the University of California-San Francisco to develop psychometrically robust executive measurement tools that would be accepted by the neurology clinical trials and clinical research communities. This effort, entitled Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER), resulted in a series of tasks targeting working memory, inhibition, set shifting, fluency, insight, planning, social cognition and behavior. We describe battery conceptualization and development, data collection, scale construction based on item response theory, and lay the foundation for studying the battery's utility and validity for specific assessment and research goals. (JINS, 2013, 19, 1–9)