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Background: Ingestion of wild mushrooms leading to toxicity is a common phenomenon every year during the rainy season in Upper Assam, India. The model for end-stage liver disease (MELD) score was developed to predict mortality in a specific group of patients with decompensated chronic liver disease. It has also been used to predict mortality in patients with acute liver failure, which is also one of the dreaded complications of mushroom toxicity. There are only a couple of studies in the world that have studied MELD score as a predictor of outcomes in patients with mushroom toxicity and to the best of our knowledge, this is the first such study done in India. Methods: In this hospital-based observational study, 35 patients aged >13 years with an alleged history of ingestion of wild mushrooms, but no other cause of hepatic dysfunction were included in this study. Disease outcome (discharged/expired) was correlated with both MELD score and day of presentation from symptom onset. Results: The mean age was 32.54 years with a male-to-female sex ratio of 4:5 among the study participants. Gastrointestinal symptoms, including loose stool, vomiting, pain abdomen, and jaundice, were the most common. The MELD score was significantly higher in patients who succumbed to the toxin (p

Background: Systemic sclerosis (SSc) is a heterogenous disease with respect to the extent of skin involvement and internal organ severity. SScspecic factors that may increase the risk of osteoporosis include chronic inammation, early menopause, immobilization, soft tissue calcication depleting calcium stores and disturbance of vitamin D metabolism in the skin, kidney and gastrointestinal tract. To assess the bone Objective: mineral density in SSc patients and its correlation with serum 25 (OH) Vitamin D. Materials and methodology: A hospital based observational study was conducted among 40 SSc patients where bone mineral density was assessed using Dual Energy X-ray Absorptiometry (DEXA) scan and classied into normal bone mass, osteopenia and osteoporosis based on obtained T-score. Serum 25 (OH) Vitamin D was estimated using competitive immunoassay method. Out of 40 SSc patients, 19 (47.5%) patients had ost Results: eopenia and 15 (37.5%) patients had osteoporosis. There were 6 (15%) patients who had normal bone mass as per DEXA lumbar spine T-score. Serum 25 (OH) Vitamin D (p=0.71) does not show statistically signicant difference between patients with normal bone mass, osteopenia, and osteoporosis. Low bone mineral density Conclusion: is highly prevalent in SSc patients as per bone mineral density measurement at lumbar spine and does not show statistical signicant correlation with serum 25 (OH) Vitamin D.

Being an environmentally friendly fuel obtained from rapeseed oil, biodiesel is used extensively in Europe. However, the dependence structure between global crude oil prices and the European prices of biodiesel and rapeseed oil is understudied and unclear. In this paper, we address this gap by utilizing asymmetric copulas and cross-quantilogram approaches on daily data. The results of the DCC-Student-t copula indicate that during bearish periods the conditional connectedness between crude oil prices and biodiesel (rapeseed oil) prices are stronger than during bullish periods, indicating increased co-movement with a decline in crude oil prices. The application of cross-quantilogram indicates that an increase in crude oil price positively influences biodiesel prices reflecting an asymmetric dependence structure among the assets. There is evidence of shifts in the dy namics of quantile dependency during periods of financial and economic turmoil. Overall, the results show a significant dependence between the global crude oil market and the European markets of biodiesel and rapeseed oil in specific periods and under specific market conditions, which have important implications for policymakers and investors.

The aim of the work is to explore structure-relaxivity relationship by observing transverse relaxivity enhancement in magnetic resonance imaging (MRI) of differently organized superparamagnetic complex ensembles of zinc ferrite isotropic/anisotropic nanosystems. We observe that superparamagnetic systems show a correlation of MRI-transverse relaxivity

Haemophilia is an inherited X-linked bleeding disorder characterised by a deficiency or absence of clotting factor VIII (haemophilia A) or IX (haemophilia B), which can cause musculoskeletal bleeding. The standard treatment for haemophilia is with factor concentrates to replace the missing or deficient clotting factor. However, there is a risk that the immune system develops antibodies against the exogenous factor, known as inhibitors. Managing patients with haemophilia and inhibitors who develop bleeding in unusual sites can be challenging for the treating physician. Here, we present a rare case of patient with severe haemophilia A who was diagnosed with inhibitors after developing bleeding in the left posterior chest wall (extra pleural haematoma). The patient was successfully managed with activated prothrombin complex concentrate (aPCC) (FEIBA: FVIII inhibitor bypassing activity; Baxter AG), and the pain and swelling gradually resolved over three weeks. This case emphasises the importance of clinical suspicion of inhibitor formation in a patient already diagnosed with haemophilia A presenting with unusual bleeding that does not respond to standard treatment.

PurposeThis study aims to examine whether there exists any relationship between corporate biodiversity reporting decision (CBRD) and corporate environmental performance (CEP).Design/methodology/approachThe primary sample contains 442 firm-year observations over a period of 13 years (2008–2020) for 34 listed Finnish companies. Based on both legitimacy theory and voluntary disclosure theory, 2 logit regression models are estimated to test the CBRD–CEP nexus. CBRD is a dichotomous variable. Three proxies for CEP, namely propensity to emit greenhouse gas (GHG), propensity to consume water and propensity to generate waste are employed.FindingsThis study finds that firms having higher propensity to consume water and generate waste are inclined to release biodiversity-related information. The findings support legitimacy theory suggesting that firms with inferior environmental performance may decide on reporting biodiversity information for legitimation purpose.Research limitations/implicationsThe study uses Finnish data and hence, the results may lack in generalizability to other national contexts.Practical implicationsThe results of this study should be valuable to policy makers for formulating mandatory biodiversity reporting standards to ensure disclosure of standard, extensive and authentic biodiversity-related information by companies. The results should also be valuable to corporate managers and eco-friendly investors.Originality/valueCorporate biodiversity reporting (CBR) is an under-researched area of environmental accounting literature. Using the Finnish context, this paper extends the existing literature by investigating whether any association exists between CBRD and CEP, which has not been examined before.

The academic literature on green energy equity markets has increased extensively over the last decade due to growing concerns about climate change and the substantial flow of investments into alternative energy markets. This study contributes by investigating the effect of climate risk on the return and volatility of green energy assets. This is one of the first papers to assess such effects using the recently developed climate policy uncertainty index as an indicator of climate risk. In particular, we seek to answer the following research questions. Firstly, does rising climate risk lead to a significant increase in green energy asset returns? Secondly, does climate risk affect the volatility of green energy assets negatively? Employing various models, we provide statistical evidence in favour of our hypotheses. Rising climate risk seems to encourage investment in alternative energy, which leads to an upward demand for green energy, which in turn increases the prices of green energy investments and decreases their volatility levels. Our analysis further shows that when climate risk increases, the correlation between crude oil and green energy returns decreases. Furthermore, green energy assets are more effective than gold for hedging oil market risk, without ignoring the hedging ability of technology stock investment. Funding Agencies|Saara and Bjorn Wahlroos foundation; Porssisaatio foundation

Substance P (SP) is a neuropeptide that has its place in the tachykinin family and helps in the transmission of neurogenic signals. SP is also a neuromodulator that plays a crucial part in pain during inflammatory processes. It is produced by the capsaicin-sensitive unmyelinated C fibers sensory neurons by the central and peripheral nervous systems. Substance P is known as a critical primary responder to most of the extreme stimuli, i.e., specifically those with the ability to destabilize the biological integrity. Hence, SP can be considered as an instantaneous system for defense, stress, healing, etc. SP is known to perform a vital role in neurogenic inflammation and the pathophysiology of acute pancreatitis. Out of these, neurogenic inflammation is responsible for acute interstitial pancreatitis as a result of oedema. SP binds itself to the G-protein coupled neurokinin-1 receptor and causes plasma leakage, cell proliferation, and invasion resulting in pancreatic cancer. SP along with comparable neuropeptides seems to be crucial targets with the capability of satisfying several unfulfilled medical requisites. This review article mainly focuses on compiling the available evidence to show that SP could be a novel therapeutic target for pancreatic diseases, and more exploration into the SP signaling pathways is the call of the hour.

Background: Chronic Myeloid Leukaemia (CML) is a myeloproliferative disorder of the haemopoietic clonal cells carrying the Philadelphia chromosome in 95% cases which results from the reciprocal translocation between long arms of chromosomes 9 and 21 t(9;22)(q34;11), leading to the formation of BCR-ABL fusion gene, that constitutively produces Tyrosine Kinase. Beyond normal activity of this enzyme is responsible for the carcinogenesis in CML. Imatinib, a tyrosine kinase inhibitor, inhibits the oncogenic pathway in CML. Imatinib has been a great success in terms of cytogenic and haematological response since its approval by FDA. Imatinib is well tolerated, but is associated with mild to moderate toxicity that can be managed by dose reductions or discontinuation. Common side effects include GI intolerance, rash and myalgia. Adherence to Imatinib is the key to complete therapeutic response but there are multiple compliance limiting factors, like unavailability, side effects and one of the recent factors being the COVID19 pandemic. This study highlights the challenges faced by the CML patients on Imatinib in terms of side effects and factors that limit the adherence to therapy. Materials and Methods: Study Design: Retrospective telephonic hospital based observational study Method: We reviewed the Chemotherapy register of Assam Medical College and Hospital and attempted to contact CML patients who have indented Imatinib in the last 5 months. Total 59 patients indented the drug in this time span, out which 27 patients could not be contacted. Remaining patients were asked regarding any complaints and compliance to the therapy after taking due consent. Result: The study involved 32 patients, 34.3% Female and 65% Male, with a median age of 48. While 37.5% patients didn’t have any side effect, most common side effect was Gastrointestinal intolerance, 31.25%(nausea, vomiting, loose stool and abdominal discomfort), followed by equal occurrence of other side effects (6.25%);myalgia, facial puffiness, weight gain, tingling sensation, skin rash, itching and one case of haematuria. Out of the 32 patients, 43.75% patients have been strictly adherent to the therapy. Among others 25%(8) patients could not take the medicine due to lockdown imposed in 2020 due to COVID19 pandemic;18.75%(6) concurrent illness; 12.5%(4) drug unavailability; 6.25%(2) poor quality of the drug and 1 patient switched to herbal medication temporarily. CONCLUSION: While one third patients didn’t have any complaint, GI intolerance is the most common among the rest. Among the other factors, the ongoing COVID19 pandemic has emerged out as an important adherence limiting factor in CML followed by concurrent illness and drug unavailability. This study emphasizes the need for ensuring the quantity, quality and delivery of the drug to an extent that is minimally affected by the pandemic and also highlights the importance of disease awareness to prevent less educated people switching to alternative treatment like herbal medications.

Cell death, survival, or growth decisions in T-cell subsets depend on interplay between cytokine-dependent and metabolic processes. The metabolic requirements of T-regulatory cells (Tregs) for their survival and how these are satisfied remain unclear. Herein, we identified a necessary requirement of methionine uptake and usage for Tregs survival upon IL-2 deprivation. Activated Tregs have high methionine uptake and usage to S-adenosyl methionine, and this uptake is essential for Tregs survival in conditions of IL-2 deprivation. We identify a solute carrier protein SLC43A2 transporter, regulated in a Notch1-dependent manner that is necessary for this methionine uptake and Tregs viability. Collectively, we uncover a specifically regulated mechanism of methionine import in Tregs that is required for cells to adapt to cytokine withdrawal. We highlight the need for methionine availability and metabolism in contextually regulating cell death in this immunosuppressive population of T cells.

BACKGROUND As defined by World Health Organization (WHO), stroke is accountable for 5 million deaths and 5 million disabled patients throughout the world. The prevalence of stroke is in rising trend in Indian subcontinent and therefore is a source of socioeconomic concern. This study was conducted to evaluate the aetiological and clinical profile in stroke patients with special reference to baseline intracranial haemorrhage (ICH) score in haemorrhagic stroke in North East India. METHODS The study was carried out among in-patients of Medicine Department at Assam Medical College and Hospital, Dibrugarh in North East India from March 2019 to February 2020. A total of 112 patients who presented with symptoms suggestive of stroke were assessed. Mean ± standard deviation was used to express continuous variables. Frequency and percentage were used to express categorical variables. Test of significance for qualitative data was assessed by chi-square test (for 2 x 2 tables). P-value less than 0.05 was taken as statistically significant. RESULTS In our study stroke was common in 40 – 60 years age group which comprised 50 % of total patients. Stroke was more common in males with a sex ratio of 1.24:1. 73.2 % of patients suffered haemorrhagic stroke and 22.3 % suffered ischemic stroke whereas 4.5 % suffered cardio-embolic stroke. Hypertension was the most prevalent and an important risk factor with 80.3 % (P = 0.001), followed by smoking with 39 % (P = 0.021), chronic alcohol consumption with 37 % (P = 0.028) and diabetes with 22 %. The most common site of haemorrhage was basal ganglia (28 %) followed by thalamus (24 %). Patients presenting with intraventricular extension, infratentorial location, low Glasgow Coma Scale (GCS) score (< 4) or having high ICH score (≥ 3) at the time of presentation were associated with increased mortality in haemorrhagic stroke (P = 0.010). CONCLUSIONS Haemorrhagic strokes (73.2 %) are the most common type. Hypertension is the most prevalent and an important risk factor (80.3 %). Basal ganglia (28 %) are the most common sites involved in haemorrhagic stroke; infratentorial location is associated with poor prognosis. Patients presenting with low GCS score (< 4) or having high ICH score (≥ 3) at the time of presentation are associated with increased mortality in haemorrhagic stroke. KEY WORDS Stroke, Hypertension, Basal Ganglia, GCS Score, ICH Score

Unlike previous studies examining the association between crude oil and renewable energy stock prices under average conditions, we employ a quantile-based regression approach offering a more comprehensive dependence structure under diverse market conditions. Using weekly data covering crude oil prices (WTI market) and three clean energy stock indices (the Wilderhill Energy Index, MAC Global Solar Energy Index, and S&P Global Clean Energy Index), quantile regression analyses provide solid evidence of the decreasing dependence of clean energy stock returns on crude oil returns. The lagged effect of WTI oil returns on clean energy stock returns is generally significant, which indicates that clean energy stock returns react differently to new information on oil returns under different market conditions. We further check for asymmetrical effects of oil returns on clean energy stock returns in various market conditions and find a strong effect of negative oil returns during bearish periods and an insignificant effect during bullish episodes.

The wound healing process is a product of three successive and overlapping phases of inflammation, proliferation and remodelling. Considerable efforts have been invested in deconstructing the intercellular crosstalk that orchestrates tissue repair, and we investigated the role of neuropeptides released from peripheral neurons upon injury in mediating these interactions. Amongst the most abundant of these neuropeptides secreted by nerves in the skin, is Substance P (SP). Given the role of dermal fibroblasts in coordinating multiple processes in the wound healing program, the effect of SP on human dermal fibroblasts of different ages was evaluated. The use of a substrate that recapitulates the mechanical properties of the in vivo tissue revealed novel effects of SP on dermal fibroblasts, including a block in inflammatory cytokine expression. Moreover, SP can promote expression of some extracellular matrix components and generates signals that regulate angiogenesis. Interestingly, the response of fibroblasts to SP was reduced concomitant with donor age. Altogether, SP acts to inhibit the inflammatory responses and promote proliferation-associated responses in an age-dependent manner in dermal fibroblasts, suggesting a role as a molecular switch between the inflammatory and proliferative phases of the wound healing response.

Digitalization has gained momentum in recent years in all sphere of life aroundthe globe. It has become an important factor of deÖning modernization, and instrumentalin speeding up economic growth by ensuring more transparency. After demonetization andemphasis on cashless transaction, digitalized mode of payment is being prioritized. Accord-ingly, government of India launched several schemes focusing on imparting training on digitalliteracy, but research shows that a section of population is still not adopting this digitaliza-tion process. This study tries to Önd the factors responsible for excluding a section of thepeople, especially the people of rural and semi urban area from this digitalized system. Ac-cordingly, a survey was conducted with the bamboo craft man of Raipur cluster of BarpetaDistrict of Assam, India, who is involved in small enterprises involving bamboo crafting.Direct interaction was being done with the respondents regarding the various problems andinconvenience faced in adapting the new system. A logit regression model has been usedto highlight the impact of various socio-economics factors, level of awareness about the newsystem of digitalization on their adaptability to the digitalized mode of payment

PurposeThe purpose of this research is to examine the impact of external assurance on the level of voluntary corporate climate change disclosures by Finnish firms.Design/methodology/approachThe sample of this study includes 228 firm-year observations over the period 2008–2015 for listed Finnish companies that have issued sustainability reports and responded to the Carbon Disclosure Project (CDP) questionnaire at least once during the sample period. The authors conduct a panel regression analysis to study the afore-mentioned linkage. In addition, the Tobit regression model is also estimated to check the robustness of our findings.FindingsThe findings suggest that assurance has a highly significant positive impact on the level of corporate climate change disclosures even after controlling for the effect of a number of control variables. Moreover, among the control variables, firm size and asset age are found to have significant effect on the extent of carbon emissions disclosure. Furthermore, the additional analysis reveals that the type of assurance providers (accounting firms vs non-accounting firms) and the type of financial auditors (Big4 financial auditors vs non-Big4 financial auditors) do not influence the level of climate change disclosure of assured companies.Research limitations/implicationsThis research is subject to certain limitations. First, the source of the data used in this research is the CDP database which has limitations in that it is a voluntary disclosure process where all the observations collected are self-reported by the responding firms. This may bias the reported findings. Second, our sample includes only listed companies and hence the results might have limited explanatory capacity for unlisted firms.Practical implicationsBy using the results of this research, corporate managers will be able to reduce the information asymmetry between various stakeholders and them through disclosure of accurate, reliable and credible environmental information. Such disclosures will, in turn, allow socially responsible investors to choose eco-friendly investments and will thus enable them to make appropriate investment decisions.Originality/valueResearch on the external assurance-corporate climate change disclosure nexus is scarce. This study addresses this gap in the nonfinancial disclosure assurance literature by demonstrating that external assurance increases the level of voluntary corporate climate change disclosure. Drawing on stakeholder-agency theory, this study views external assurance as a monitoring structure that potentially curbs the monitoring problem between corporate managers and other stakeholders and increases the amount of climate change disclosures making a possible avenue for the reduction of the information asymmetry between them.

Tourism has emerged as one of the leading components of aggregate economic growth in most developed economies, especially in the UK, where it is predicted to grow at an annual rate of 3.8% through 2025. Because tourism demand represents individuals’ choice between leisure and work, a persistence of negative shocks, such as Brexit uncertainty, can be detrimental to the growth of tourism via its impact on agents’ utility function of a directed consumption of leisure for a specific country. This note fills a gap in the literature by providing an econometric estimate of time-varying volatility in tourism demand following Brexit-driven Economic Policy Uncertainty. Using seasonally adjusted and trend-extracted tourist arrival series along with Brexit uncertainty, we find a strong evidence of long-run persistence in (asymmetric) volatility in tourist arrival. In particular, the BREXIT referendum appeared to create ambiguity among international visitors to the UK. Our results have important policy implications.

We contribute to the scarce literature on the oil market volatility index (OVX) by examining the presence of time‐varying jumps in OVX and by assessing the ability of OVX to predict the conditional variance of crude oil returns. Using a GARCH‐jump model, we find evidence that OVX is characterized by jump behaviour that tends to vary over time. Further analysis indicates that accounting for the jump behaviour of OVX helps improve the conditional variance forecasts of crude oil returns. Since the studied features of OVX play a crucial role in asset pricing and risk analyses, our findings have policy implications related to refining volatility prediction models and risk measures.

Unlike previous studies, we examine which of the implied volatilities of US stock and crude oil markets are more suitable and effective hedge for the downside risk of US travel and leisure (T&L) stocks. Using the corrected dynamic conditional correlation process, the results show that the T&L stock index is more negatively and more consistently correlated with the implied volatility of crude oil prices, suggesting that the oil implied volatility is a more suitable hedging asset. Similar results are reported for France, the United Kingdom, and developed markets. They are robust to the frequency of the data and model specification. Furthermore, the hedge ratios vary over time, which requires a regular update of hedged positions. Importantly, the highest hedge effectiveness is associated with the oil implied volatility.

Laboratory and field efficacy of certain neonicotinoids, green nanoparticles and botanicals is reported against diamondback moth (DBM), Plutella xylostella. In laboratory bioassay, the LC50 of chlorantraniliprole, novaluron, flubendiamide, silver nanoparticles (np), zinc np, neem oil, tulsi extract, dhatura extract and imidacloprid (standard check) were found to be 0.004, 0.008, 0.005, 0.039, 0.013, 0.893, 0.615, 0.738 and 0.001 per cent respectively after 24 h of exposure and 0.040, 0.006, 0.100, 0.028, 0.008, 0.116, 0.092,0.133 and 0.069 per cent respectively after 48 h. The order of toxicity to DBM on the basis of LC50 values was imidacloprid> chlorantraniliprole>flubendiamide>novaluron> zinc np> silver np>tulsi extract >dhatura extract >neem oil for the exposure period of 24 h and novaluron> zinc np> silver np> chlorantraniliprole> imidacloprid>tulsi extract >flubendiamide>neem oil >dhatura extract for the exposure period of 48 h respectively. In field application, chlorantraniliprole10 g ai ha⁻¹ was the most effective in bringing down the population of DBM (78.70, 82.00, 87.50, 86.40 and 85.30 per cent) at 1,3,5,7 and 15 d after spraying (DAS) respectively, while the lowest population reduction (12.50, 17.00, 15.90, 15.90 and 13.60 per cent) was found with dhatura extract 0.2 mLL⁻¹ at 1, 3, 5, 7 and 15 DAS.

Introduction Haemophilia is an X-linked congenital bleeding disorder due to deficiency of coagulation factor VIII (in haemophilia A) or factor IX (in haemophilia B) caused by mutations of the respective clotting factor genes. Treatment involves the administration of an appropriate dose of factor concentrate, as soon as possible, in the event of any bleeding episode. In low-resource settings, such as Northeast India, where factor concentrates are not widely available, people with haemophilia (PwH) may bleed profusely even from trivial external injuries, warranting transfusion of blood or blood products. We previously reported on the use of a low cost, foam-based haemostatic patch to treat an external bleed in a single patient. In this study, we investigated its use to treat a range of external injuries in PwH presenting at Assam Medical College and Hospital. Method Over 24 months, eligible PwH with external injuries attending our haemophilia clinic were treated with a topical haemostatic patch (VELSEAL-T) at the target bleeding site. The time to cessation of bleeding was recorded and the wound sites evaluated after haemostasis to monitor efficacy and safety. Results Out of 72 individuals with bleeding disorders who volunteered to participate, 59 cases of external bleeding in 48 PwH were eligible for inclusion in the study. Nine (15.3%) had aberration wounds, 24 (40.7%) cut wounds, 21 (35.6%) tooth and/or gum bleeding and five (8.4%) bleeding from puncture wounds. The average time required for achievement of haemostasis was 9.9 (±4.7) minutes. Aberration wounds required the least amount of time for haemostasis at 7.3 (±4.4) minutes. Cut wounds required a mean time of 8.5 (±2.9) minutes; puncture wounds required 9.0 (±3.1) minutes; gum bleeding required the longest time to achieve haemostasis with a mean of 12.7 (±5.6) minutes. Conclusion The use of this topical haemostatic patch has been shown to be beneficial in the treatment of external injuries in PwH, and provides a good treatment option in resource-constrained areas. A larger controlled study would be helpful to further investigate its efficacy and safety.

Background Patients with haemophilia who are not adequately treated experience a lifetime burden of joint complications and loss of functional ability due to repeated bleeding episodes caused by low levels of clotting factor VIII or IX in the blood. These complications can significantly impact day-to-day life, including active participation in school and academic study in children with haemophilia (CwH). Treatment with factor replacement therapy can help to prevent this, but access to factor has been challenging in low-resource settings such as Northeast India. This study shows the impact of factor replacement therapy on bleeding episodes, joint complications and school absence among CwH in this setting. Methods A retrospective observational study was undertaken to examine the impact of receiving regular factor replacement therapy (prophylaxis or on demand) on school absences among CwH registered with the haemophilia treatment centre at Assam Medical College and Hospital. Annual bleed rate (ABR), Haemophilia Joint Health Score (HJHS) and Functional Independence Score in Haemophilia (FISH) were also assessed. Results Thirty-eight CwH were eligible for the study; 26 (68.4%) were on prophylaxis therapy and 12 (31.5%) received on-demand therapy. In the year before starting regular treatment, the mean ABR was 37.8 (+20.0), HJHS was 31.1 (+18.1) and mean FISH score was 21.1 (+4.2). At the end of the study period the mean (+SD) ABR in prophylactic therapy was significantly lower at 5.8 (+4.6) (p Conclusions Treatment with factor replacement significantly reduces school absence in CwH and correlates strongly with joint health and functional improvement, with the effect slightly better with prophylaxis than on-demand therapy. Low dose prophylaxis is a good treatment option in low-resource settings, but improvements are also needed in rates of diagnosis.

It is increasingly clear that cell death, survival or growth decisions of T lymphocyte subsets depend on interplay between cytokine-dependent and metabolic processes. What the metabolic requirements of T regulatory cells (Tregs) for their survival are, and how these requirements are satisfied remain to be fully understood. In this study, we identified a necessary requirement of methionine uptake and utilization for Tregs survival upon interleukin 2 (IL-2) deprivation. Activated Tregs have high methionine uptake and consumption to S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH). This methionine uptake is essential for Tregs survival, and is regulated by Notch1 activity. Notch1 controls the expression of the solute carrier protein SLC43A2 transporter during IL-2 deprivation. SLC43A2 is necessary for sufficient methionine uptake, and determines Tregs viability upon IL-2 withdrawal. Collectively, we identify a specifically regulated mechanism of methionine import in Tregs that is necessary for the survival of these cells. This highlights the need for methionine availability and metabolism in contextually regulating cell death in an immunosuppressive population of T lymphocytes.

We examine the presence of outliers and time-varying jumps in the returns of four major cryptocurrencies (Bitcoin, Ethereum, Ripple, Dogecoin, Litecoin), and a broad cryptocurrency index (CCI30). The results indicate that only Bitcoin returns are contaminated with outliers. Time-varying jumps are present in Bitcoin, Litecoin, Ripple, and the cryptocurrency index. Notably, the presence of jumps in Bitcoin is significant after correcting for outliers. The main findings point to a price instability in some major cryptocurrencies and thereby the importance of accounting for large shocks and time-varying jumps in modelling volatility in the debatable cryptocurrency markets.

Tetanus is a rare, severe, and potentially life-threatening disease caused by Clostridium tetani, which accounted 58,900 deaths worldwide in 2013.1 Usually tetanus is generalized, rarely it can be localized also. 20-30% of cases will not have any puncture wound. In this case report, we present a case of tetanus with rare manifestation (localized tetanus presented with trismus without any puncture wound). Multiple rare associations like tetanus presenting with trismus, tetanus occurring in the absence of puncture wound strengthens the need for reporting this case which if left unnoticed would have been detrimental to the patient.