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Traditional censorship revolves around blocking access to some websites (or services) over the Internet. However, recently there has been a rise in the events of an extreme form of censorship viz., deliberate Internet shutdown, leading to complete Internet disconnection, severely impacting lives in such regions. Naturally, these shutdowns render all existing circumvention schemes unusable. Thus, we present Dolphin, a first of its kind system that can provide access to lightweight and delay tolerant Internet applications (email, tweets, news snippets, etc.) during Internet shutdowns. Dolphin uses the cellular voice channel to transmit data bits. A user in the shutdown region (who wishes to access these applications) requires a peer in non-shutdown region to send and retrieve content on its behalf. The data bits between the peers are sent by first encoding them into audio and then transmitting them over a cellular voice call. We overcome multiple challenges while designing and implementing Dolphin. E.g., the cellular voice channel is inherently lossy and unreliable. But the Internet applications need reliable transfers. Thus, in Dolphin we develop a TCP-style reliability layer to overcome the losses that works atop any underlying encoding and modulation scheme. Further, to evade eavesdroppers over the insecure voice channel, we provide end-to-end confidentiality. Also, Dolphin can function even without human intervention, by using cellular voice automation services. We experimentally show that Dolphin works for Internet applications, by testing it for sending email, tweets and accessing news snippets. All these applications take a few minutes to be accessed (e.g., a 500 character email was received in under 2 minutes).

Cryptocurrency systems can be subject to deanonimization attacks by exploiting the network-level communication on their peer-to-peer network. Adversaries who control a set of colluding node(s) within the peer-to-peer network can observe transactions being exchanged and infer the parties involved. Thus, various network anonymity schemes have been proposed to mitigate this problem, with some solutions providing theoretical anonymity guarantees. In this work, we model such peer-to-peer network anonymity solutions and evaluate their anonymity guarantees. To do so, we propose a novel framework that uses Bayesian inference to obtain the probability distributions linking transactions to their possible originators. We characterize transaction anonymity with those distributions, using entropy as metric of adversarial uncertainty on the originator's identity. In particular, we model Dandelion, Dandelion++ and Lightning Network. We study different configurations and demonstrate that none of them offers acceptable anonymity to their users. For instance, our analysis reveals that in the widely deployed Lightning Network, with 1% strategically chosen colluding nodes the adversary can uniquely determine the originator for about 50% of the total transactions in the network. In Dandelion, an adversary that controls 15% of the nodes has on average uncertainty among only 8 possible originators. Moreover, we observe that due to the way Dandelion and Dandelion++ are designed, increasing the network size does not correspond to an increase in the anonymity set of potential originators. Alarmingly, our longitudinal analysis of Lightning Network reveals rather an inverse trend -- with the growth of the network the overall anonymity decreases.

Contains fulltext : 286832.pdf (Publisher’s version ) (Open Access) BACKGROUND: Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19. METHODS: For this prospective outcomes validation study, we developed a radiotranscriptomic platform that uses RNA sequencing data from human internal mammary artery biopsies to develop novel radiomic signatures of vascular inflammation from CT angiography images. We then used this platform to train a radiotranscriptomic signature (C19-RS), derived from the perivascular space around the aorta and the internal mammary artery, to best describe cytokine-driven vascular inflammation. The prognostic value of C19-RS was validated externally in 435 patients (331 from study arm 3 and 104 from study arm 4) admitted to hospital with or without COVID-19, undergoing clinically indicated pulmonary CT angiography, in three UK National Health Service (NHS) trusts (Oxford, Leicester, and Bath). We evaluated the diagnostic and prognostic value of C19-RS for death in hospital due to COVID-19, did sensitivity analyses based on dexamethasone treatment, and investigated the correlation of C19-RS with systemic transcriptomic changes. FINDINGS: Patients with COVID-19 had higher C19-RS than those without (adjusted odds ratio [OR] 2·97 [95% CI 1·43-6·27], p=0·0038), and those infected with the B.1.1.7 (alpha) SARS-CoV-2 variant had higher C19-RS values than those infected with the wild-type SARS-CoV-2 variant (adjusted OR 1·89 [95% CI 1·17-3·20] per SD, p=0·012). C19-RS had prognostic value for in-hospital mortality in COVID-19 in two testing cohorts (high [≥6·99] vs low [

Anonymous VoIP calls over the Internet holds great significance for privacy-conscious users, whistle-blowers and political activists alike. Prior research deems popular anonymization systems like Tor unsuitable for providing the requisite performance guarantees that real-time applications like VoIP need. Their claims are backed by studies that may no longer be valid due to constant advancements in Tor. Moreover, we believe that these studies lacked the requisite diversity and comprehensiveness. Thus, conclusions from these studies, led them to propose novel and tailored solutions. However, no such system is available for immediate use. Additionally, operating such new systems would incur significant costs for recruiting users and volunteered relays, to provide the necessary anonymity guarantees. It thus becomes an imperative that the exact performance of VoIP over Tor be quantified and analyzed, so that the potential performance bottlenecks can be amended. We thus conducted an extensive empirical study across various in-lab and real world scenarios to shed light on VoIP performance over Tor. In over half a million calls spanning 12 months, across seven countries and covering about 6650 Tor relays, we observed that Tor supports good voice quality (Perceptual Evaluation of Speech Quality (PESQ) >3 and one-way delay <400 ms) in more than 85% of cases. Further analysis indicates that in general for most Tor relays, the contentions due to cross-traffic were low enough to support VoIP calls, that are anyways transmitted at low rates (

Decoy Routing (DR), a promising approach to censorship circumvention, uses routers (rather than end hosts) as proxy servers. Users of censored networks, who wish to use DR, send specially crafted packets, nominally addressed to an uncensored website. Once safely out of the censored network, the packets encounter a special router (the Decoy Router) which identifies them using a secret handshake, and proxies them to their true destination (a censored site). However, DR has implementation problems: it is infeasible to reprogram routers for the complex operations required. Existing DR solutions fall back on using commodity servers as a Decoy Router. But as servers are not efficient at routing, most web applications show poor performance when accessed over DR. A further concern is that the Decoy Router has to inspect all flows in order to identify the ones that need DR. This may itself be a breach of privacy for other users (who neither require DR nor want to be monitored). In this paper, we present a novel DR system, Siege- Breaker (SB), which solves the aforementioned problems using an SDN-based architecture. Previous proposals involve a single unit which performs all major operations (inspecting all flows, identifying the DR requests and proxying them). In contrast, SB distributes the tasks for DR among three independent modules. (1) The SDN controller identifies DR requests via a covert, privacy preserving scheme, and does not need to inspect all flows. (2) The reconfigurable SDN switch intercepts packets, and forwards them to a secret proxy efficiently. (3) The secret proxy server proxies the client’s traffic to the censored site. Our modular, lightweight design achieves performance comparable to direct TCP downloads, for both in-lab setups, and Internet based tests involving commercial SDN switches.

Treatment with immune checkpoint blockade (ICB) frequently triggers immune-related adverse events (irAEs), causing considerable morbidity. In 214 patients receiving ICB for melanoma, we observed increased severe irAE risk in minor allele carriers of rs16906115, intronic to IL7. We found that rs16906115 forms a B cell-specific expression quantitative trait locus (eQTL) to IL7 in patients. Patients carrying the risk allele demonstrate increased pre-treatment B cell IL7 expression, which independently associates with irAE risk, divergent immunoglobulin expression and more B cell receptor mutations. Consistent with the role of IL-7 in T cell development, risk allele carriers have distinct ICB-induced CD8+ T cell subset responses, skewing of T cell clonality and greater proportional repertoire occupancy by large clones. Finally, analysis of TCGA data suggests that risk allele carriers independently have improved melanoma survival. These observations highlight key roles for B cells and IL-7 in both ICB response and toxicity and clinical outcomes in melanoma.

NP105-113-B*07:02 specific CD8+ T-cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02 specific T-cell clones and single cell sequencing were performed concurrently, with functional avidity and anti-viral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with TCR usage, transcriptome signature, and disease severity (acute N=77, convalescent N=52). We demonstrated a beneficial association of NP105-113-B*07:02 specific T-cells in COVID-19 disease progression, linked with expansion of T-cell precursors, high functional avidity and anti-viral effector function. Broad immune memory pools were narrowed post-infection but NP105-113-B*07:02 specific T-cells were maintained 6 months after infection with preserved anti-viral efficacy to the SARS-CoV-2 Victoria strain, as well as new Alpha, Beta and Gamma variants. Our data shows that NP105-113-B*07:02 specific T-cell responses associate with mild disease and high anti-viral efficacy, pointing to inclusion for future vaccine design.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design and personalized medicine approaches for COVID-19., Graphical Abstract, A multi-omic analysis of patient blood samples reveals both similarities and specific features of COVID-19 when compared with samples obtained from sepsis or influenza patients which could yield better targetted therapies for severe COVID-19.

NP105–113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105–113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105–113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105–113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105–113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design. Peng et al. find that immunodominant cytotoxic T lymphocytes (CTLs) specific for NP105–113-B*07:02 are associated with reduced COVID-19 severity. Mechanistically, NP105–113-B*07:02-specific CTLs show potent antiviral functionality and may represent rational T cell vaccine targets.

Recurrent malignant solid pseudopapillary neoplasms of the pancreas (SPNP) are rare tumors with unpredictable clinical and histopathological features. There is a lack of consensus regarding utilization of adjuvant modalities in conjunction with or in lieu of curative metastatectomy. We present a remarkable case where Yttrium-90 selective internal radiation therapy (Y-90 SIRT) was successfully utilized to elucidate underlying tumor biology and aid resection of a large multifocal recurrent metastatic SPNP in the right hemi-liver of a 59-year-old female. Thus, in cases where curative metastatectomy remains the treatment goal in management of recurrent and/or metastatic SPNPs, Y-90 SIRT is a safe and effective adjunct treatment to facilitate curative resection.

Background: Solid pseudopapillary neoplasm of pancreas is a rare tumor with a low potential for metastasis and recurrence. Long-term outcomes after surgical resection are excellent and recurrences after an R0 resection are extremely rare. Case Presentation: We present an unusual case of a 42-year-old man who had a recurrence of his solid pseudopapillary tumor 4 years after undergoing a distal pancreatectomy and splenectomy and then again a year after his reresection. Conclusions: The lack of histological features deemed to be suggestive of a malignant variant and the aggressive clinical course seen in this case is remarkable. It underscores the fact that despite the low incidence, recurrences of solid pseudopapillary neoplasms of the pancreas do occur and it can be very difficult to predict malignant potential based on radiological or histopathological features.

In the age of increasingly pervasive sensing applications, measurement of unknown pattern phenomena resulting in novel data presents a challenge to selection of appropriate modeling tools. Because there is no rich history of domain knowledge, one can easily make early commitments to poor modeling choices. Data transformation, a solution in effort to modify the data’s geometry, can make important regularities more clear. The wrong transformation can damage the very pattern information one seeks to identify. In contrast to data transformation, we contribute an alternative method, range transformation focusing on altering the measurement tool. As a function, a model maps data inputs to a range. Focusing on transformations of the model’s range, we can find a generally applicable way to alter the model’s properties to best suit the data. Every modification to a function class, something we call editing the function, results in a change to the original function’s range. This work contributes a method for modifying a broad class of models to suit novel data through range transformation. We investigate range transformation for a class of information theoretic transformations and evaluate impact on classification and clustering. We also develop an optimization-based framework employing range transformation based on desired geometric properties and use it to improve a widely used model, k-means clustering.

Assess the performance characteristics of axillary ultrasound (AUS) for accurate exclusion of clinically significant axillary lymph node (ALN) disease.Sentinel lymph node biopsy (SLNB) is currently the standard of care for staging the axilla in patients with clinical T1-T2, N0 breast cancer. AUS is a noninvasive alternative to SLNB for staging the axilla.Patients were identified using a prospectively maintained database. Sensitivity, specificity, and negative predictive value (NPV) were calculated by comparing AUS findings to pathology results. Multivariate analyses were performed to identify patient and/or tumor characteristics associated with false negative (FN) AUS. A blinded review of FN and matched true negative cases was performed by 2 independent medical oncologists to compare treatment recommendations and actual treatment received. Recurrence-free survival was described using Kaplan-Meier product limit methods.A total of 647 patients with clinical T1-T2, N0 breast cancer underwent AUS between January 2008 and March 2013. AUS had a sensitivity of 70%, NPV of 84%, and PPV of 56% for the detection of ALN disease. For detection of clinically significant disease (2.0 mm), AUS had a sensitivity of 76% and NPV of 89%. FN AUS did not significantly impact adjuvant medical decision making. Patients with FN AUS had recurrence-free survival equivalent to patients with pathologic N0 disease.AUS accurately excludes clinically significant ALN disease in patients with clinical T1-T2, N0 breast cancer. AUS may be an alternative to SLNB in these patients, where axillary surgery is no longer considered therapeutic, and predictors of tumor biology are increasingly used to make adjuvant therapy decisions.

In this work we present a detailed study of the Internet censorship mechanism in India. We consolidated a list of potentially blocked websites from various public sources to assess censorship mechanisms used by nine major ISPs. To begin with, we demonstrate that existing censorship detection tools like OONI are grossly inaccurate. We thus developed various techniques and heuristics to correctly assess censorship and study the underlying mechanism used by these ISPs. At every step we corroborated our finding manually to test the efficacy of our approach, an exercise largely ignored by several others. We fortify our findings by adjudging the coverage and consistency of censorship infrastructure, broadly in terms of average number of network paths and requested domains the infrastructure censors. Our results indicate a clear disparity among the ISPs, on how they install censorship infrastructure. For instance, in Idea network we observed the censorious middleboxes in over 90% of our tested intra-AS paths, whereas for Vodafone, it is as low as 2.5%. We conclude our research by devising our own novel anti-censorship strategies, that does not depend on third party tools (like proxies, Tor and VPNs etc.). We managed to access all blocked websites in all ISPs under test.

Objective To study the validity of smartphone otoscopy. Setting Ear, nose, and throat (ENT) outpatient clinic of a tertiary care hospital in eastern India. Study Design Experimental study design to compare the efficacy of smartphone otoscopy with otoendoscopes. Subjects and Methods One hundred tympanic membranes (TMs) of 50 patients were examined and photographed by third-year senior residents (6 years of ENT training) using a zero-degree otoendoscope. The same 100 ears were then examined using a smartphone. Assistive light of the phone was used to illuminate the ear canal. The camera of the phone was focused to visualize and photograph the TM. Results Compared with the gold-standard otoendoscopes, smartphones could correctly diagnose 75% of the cases. Sensitivity and specificity of smartphone otoscopy were 87.8% and 80%, respectively. Positive predictive value was 90.6%, whereas negative predictive value was 75%. Smartphone otoscopy could correctly diagnose 88.57% of normal TMs, 86.36% of retracted TMs, and 82.85% of perforated TMs. Conclusion This modality of “smart otoscopy” has no added cost and can be used by most doctors after minimal training. It is an excellent teaching tool and can be used universally even in resource-limited settings.

Optical communication network promises to deliver an unmatched data transmission speed with high capacity and bandwidth. However, one could never fully exploit the astonishing speed of light in communication as modern day electronic devices, installed in optical networks, could never stand up to the requirements of the light speed transmission. The optical systems have some serious limitations which include its inability for bit-level optical processing, slow switching and lack of efficient all-optical memory. Switching in optical networks are carried out by electronic devices. These devices rely on repeated O-E-O conversion of incoming data for switching activities, which adversely affect the optical speed. The electronic devices also act as a hurdle during optical system up-gradation as each time it needs to be replaced or upgraded. If the optical switching could be done in optical domain without the need for unwanted conversions, the use of electronic devices could be eliminated. This would not only bolster the speed of optical network but will also reduce the cost of optical system.

Adenoviral (Ad) vector vaccines represent one of the most promising modern vaccine platforms, and Ad vector vaccines are currently being investigated in human clinical trials for infectious disease and cancer. Our studies have shown that specific targeting of adenovirus to dendritic cells dramatically enhanced vaccine efficacy. However, this was achieved using a molecular adapter, thereby necessitating a two component vector approach. To address the mandates of clinical translation of our strategy, we here sought to accomplish the goal of DC targeting with a single-component adenovirus vector approach. To redirect the specificity of Ad vector vaccines, we replaced the Ad fiber knob with fiber-fibritin chimeras fused to DC1.8, a single-domain antibody (sdAb) specific for murine immature DC. We engineered a fiber-fibritin-sdAb chimeric molecule using the coding sequence for DC1.8, and then replaced the native Ad5 fiber knob sequence by homologous recombination. The resulting Ad5 virus, Ad5FF1.8, expresses the chimeric fiber-fibritin sdAb chimera. Infection with Ad5FF1.8 dramatically enhances transgene expression in DC2.4 dendritic cells compared with infection with native Ad5. Ad5FF1.8 infection of bone marrow-derived DC demonstrates that Ad5FF1.8 selectively infects immature DC consistent with the known specificity of DC1.8. Thus, sdAb can be used to selectively redirect the tropism of Ad5 vector vaccines, providing the opportunity to engineer Ad vector vaccines that are specifically targeted to DC, or specific DC subsets.

Celiac disease is a multisystem disease, and the liver is affected in a subset of patients. We herein present a case series of 25 patients with celiac disease who had evidence of cirrhosis of the liver. We retrospectively reviewed the case records of patients with celiac disease having concomitant cirrhosis. The diagnosis of celiac disease was made on the basis of the modified European Society of Pediatric Gastroenterology, Hepatology, and Nutrition criteria. Of 25 patients (nine males; mean age 28.8 ± 16.6 years) with celiac disease and cirrhosis, 17 patients presented predominantly with cirrhosis, while 8 presented primarily with celiac disease. Five patients had known cause of cirrhosis (autoimmune hepatitis, three; PBC, one; hepatic venous outflow tract obstruction, one); the remaining 20 were cryptogenic. Gluten-free diet led to improvement in diarrhea and anemia and to a better control of ascites and other features of liver failure. Some patients with cryptogenic cirrhosis have coexistent celiac disease, and they show response to gluten-free diet. Patients with cryptogenic cirrhosis should be screened for celiac disease.

Epithelial-mesenchymal transition (EMT) is an important biologic process that has been implicated in cancer metastasis. Epithelial cell adhesion molecule (EpCAM) is expressed at the basolateral membrane of most normal epithelial cells, but is overexpressed in many epithelial cancers. In our studies of the role of EpCAM in cancer biology, we observed that EpCAM expression is decreased in mesenchymal-like primary cancer specimens in vivo, and following induction of EMT in cancer cell lines in vitro. Extracellular signal-related kinase (ERK) is a key regulator of EMT. We observed that EpCAM expression is decreased with activation of the ERK pathway in primary cancer specimens in vivo and in cancer cell lines in vitro. In experimental models, growth factor stimulation and/or oncogene-induced ERK2 activation suppressed EpCAM expression, whereas genetic or pharmacologic inhibition of the ERK pathway restored EpCAM expression. In detailed studies of the EpCAM promoter region, we observed that ERK2 suppresses EpCAM transcription directly by binding to a consensus ERK2 binding site in the EpCAM promoter, and indirectly through activation of EMT-associated transcription factors SNAI1, SNAI2, TWIST1, and ZEB1, which bind to E-box sites in the EpCAM promoter. Surprisingly, EpCAM appears to modulate ERK activity. Using multiple cell lines, we demonstrated that specific ablation of EpCAM resulted in increased ERK pathway activity, SNAI2 expression, migration and invasion, whereas forced expression of EpCAM resulted in decreased ERK pathway activity, decreased SNAI2 expression, migration and invasion. These observations provide important insights into the regulation of EpCAM expression during EMT, demonstrate an unexpected role for EpCAM in the regulation of ERK, and define a novel double-negative feedback loop between EpCAM and ERK that contributes to the regulation of EMT. These studies have important translational implications as both EpCAM and ERK are currently being targeted in human clinical trials.

We aimed to determine the prevalence of coeliac disease among children with short stature at a tertiary care centre and to define the predictors for coeliac disease, if any, in them.In this retrospective study, we reviewed the case records of children and adolescents with growth retardation attending the Paediatric Endocrinology Clinic from January 2008 to June 2011. All patients underwent the multi-tier stratified diagnostic protocol for complete evaluation of short stature. Coeliac disease was screened using IgA-anti-tissue transglutaminase antibody. The diagnosis of coeliac disease was made on the basis of the modified European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria.Of 432 patients (238 boys) who presented with short stature, 72 (16.7%) had physiological, while 360 (83.3%) had pathological causes. Endocrine causes were growth hormone deficiency (86 patients, 19.9%), hypopituitarism (31, 7.2%), hypothyroidism (22, 5.1%) and others (7, 1.6%). The systemic causes were: coeliac disease (47, 10.9%), haematological diseases (14, 3.2%), renal diseases (11, 2.5%) and others (24, 5.6%). Chronic diarrhoea (OR 15.7, 95% CI 7.8-31.5) and anaemia (OR 4.9, 95% CI 1.9-12.7]) were significant predictors for coeliac disease in patients with short stature. There was a definite response to gluten-free diet in them and the mean (SD) growth velocity measured over at least 6 months of gluten-free diet was 8.1 (3.0) cm/year.Nearly 11% of patients presenting with short stature have coeliac disease. In these patients chronic diarrhoea and anaemia were significant predictors of coeliac disease.

The development of next generation sequencing technologies has revolutionized our understanding of how specific genetic events contribute to cancer initiation and progression. Dramatic improvements in instrument design and efficiency, combined with significant cost reductions has permitted a systematic analysis of the mutational landscape in a variety of cancer types. At the same time, a detailed map of the cancer mutanome in individual cancers offers a unique opportunity to develop personalized cancer vaccine strategies targeting neoantigens. Recent studies in both preclinical models and human cancer patients demonstrate that neoantigens (1) are important targets following checkpoint inhibition therapy, (2) have been identified as the target of adoptive T cell therapies, and (3) can be successfully targeted with personalized vaccines. Taken together, these observations provide strong rationale for the clinical translation of personalized cancer vaccines.

Background Dyspepsia is a common symptom in residents of Leh, a high-altitude region in Ladakh, India. Helicobacter pylori related gastritis is a common cause of such symptoms. However data regarding this association at high altitudes is sparse. Aim To investigate the demographic, endoscopic and histopathology findings in patients presenting with dyspeptic symptoms in the high-altitude region of Leh. Methods: A cross-sectional study was done in 84 patients with dyspeptic symptoms, attending the outpatient department of local government hospital in Leh. Demographic details, endoscopy, histopathology of upper gastrointestinal biopsies and microbiology culture of gastric/duodenal aspirates were studied. Results The mean age was 38.4 years with 42% being males. Indigenous foods with high-salt content were consumed by 75% of patients. Epigastric pain was the most frequent symptom (in 96%) and pain radiating to the back was another peculiar symptom seen in 49% of patients. The predominant finding on endoscopy was antral gastritis in 71% of patients. Nodular gastritis was seen in 18% of patients. H. pylori was documented in 93% and histopathology revealed mild-to-moderate inflammation in 93% and mild-to-moderate atrophy in 90% of patients. Colonization with Gram-negative bacilli was observed in gastric/duodenal aspirate cultures. Conclusion Dyspepsia at high-altitude commonly presents as pain radiating to the back with a very high (90%) prevalence of H. pylori, endoscopic findings of antral gastritis and nodular gastritis, and atrophic gastritis in biopsies. Further investigations are needed to determine whether these observations are related to the high-altitude or the high-salt content in their diet and also whether these further translate to carcinogenesis.

There is an increasing awareness for recognition of sleep disorders in India; however, there is still a huge gap in the number of people suffering from various sleep disorders, in the community versus those visiting hospital clinics for the same. Ours is a neurology services-based sleep disorders clinic, which has evolved successfully over the last decade. In this study, we aimed to evaluate the changes in referral patterns and distribution of various sleep disorders in the patients presenting to the clinic. Materials and Methods: This is a retrospective chart review-based study on all patients seen over an 8-year period, divided into 2 groups comprising of patients seen during the first 4 years versus those seen over the next 4 years. Only those patients who had the sleep disorder as their presenting manifestation and those who had been formally interviewed with a pre-structured questionnaire detailing about the main features of the common sleep disorders according to the ICSD-R were included. Patients, in whom the sleep disorder could be clearly attributable to another neurological or systemic disorder, were excluded. Statistical analysis was carried out to identify the differences between the two groups as regards the distribution of various sleep disorders and other clinical data. Results: Among 710 patients registered in the clinic, 469 were included for analysis and 222 patients formed group 1 while 247 formed group 2. The main differences observed were in the form of a clear increase in the percentage of patients with sleep-related breathing disorders, sleep-related movement disorder, and the hypersomnias on comparison of distribution over the first 4 years versus the last 4 years; while a clear decline was seen in the number of patients with insomnia and parasomnias. A 3-fold increase was observed in the number of patients in whom polysomnography was obtained. Conclusion: The distribution of various sleep disorders as seen in a neurology service-based sleep clinic is demonstrated in this study. Increasing referrals for sleep-disordered breathing, restless legs syndrome, and fewer referrals for insomnia and parasomnias might reflect on changing physician and patient awareness in our community.

To review the disease course in patients with steroid sensitive nephrotic syndrome (SSNS) and the factors that determine outcomeRetrospective, analyticalPediatric Nephrology Clinic at referral center in North IndiaAll patients with SSNS evaluated between 1990 and 2005 INTERVENTION: NoneDisease course, in patients with at least 1-yr follow up, was categorized as none or infrequent relapses (IFR), frequent relapses or steroid dependence (FR), and late resistance. Details on complications and therapy with alternative agents were recorded.Records of 2603 patients (74.8% boys) were reviewed. The mean age at onset of illness and at evaluation was 49.7±34.6 and 67.5±37.9 months respectively. The disease course at 1-yr (n=1071) was categorized as IFR in 37.4%, FR in 56.8% and late resistance in 5.9%. During follow up, 224 patients had 249 episodes of serious infections. Alternative medications for frequent relapses (n=501; 46.8%) were chiefly cyclophosphamide and levamisole. Compared to IFR, patients with FR were younger (54.9±36.0 vs. 43.3±31.4 months), fewer had received adequate (=8 weeks) initial treatment (86.8% vs. 81.7%) and had shorter initial remission (7.5±8.6 vs. 3.1±4.8 months) (all P0.001). At follow up of 56.0±42.6 months, 77.3% patients were in remission or had IFR, and 17.3% had FR.A high proportion of patients with SSNS show frequent relapses, risk factors for which were an early age at onset, inadequate initial therapy and an early relapse.

Colorectal cancer (CRC) remains one of the major causes of death worldwide, despite steady improvement in early detection and overall survival over the past decade. Current treatment paradigms, with chemotherapy and biologics, appear to have reached their maximum benefit. Immunotherapy, especially with checkpoint inhibitors, has shown considerable clinical benefit in various cancers, including mismatch-repair-deficient CRC. This has led to the planning and initiation of several clinical trials evaluating novel immunotherapy agents—as single agents, combinations and in conjunction with chemotherapy—in patients with CRC. This article reviews biological and preclinical data for checkpoint inhibitors and discusses various immunotherapy trials in CRC, as well as current efforts in CRC immunotherapy.