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The aim of the study was to determine the efficacy of lower concentration of Atropine 0.01% in promoting unaided visual acuity and slowing down the progression of myopia in children over 6 months. It was a hospital-based comparative study in the outpatient department of Ophthalmology, AL, LT, ACD, PPD, SPD, PGP were taken by Lenstar and Lensometer.The Comparative study was performed on 60 children from 9 to 15 years age group with initial myopic spherical equivalence from 0.5 to 6.00 D. The children were screened for visual acuity for distance and near using Snellen’s chart. Cycloplegic Refraction was done to know the presence of Refractive Errors. This study was approved by IRB Ethical Committee. (SCAHS/IRB/2022/JULY/420).The inclusion criteria include Ammetropic children with no binocular vision anomalies and no history of ocular disease. The primary outcome was the rate of myopic progression after 6 months. The participants were instructed to use Atropine 0.01% eye drops during night times for 6 months and the rate of myopic progression and the spherical equivalence, axial length, lens thickness, anterior chamber depth, photopic and scotopic pupil diameter were re-assessed to compare the progression of myopia in the children. Sixty children enrolled for six months study in which the mean progression of myopia was found to be within 0.27D and axial elongation shows 0.23 mm changes respectively, whereas there were no significant changes in the anterior chamber depth, lens thickness, photopic and scotopic pupil diameter before and after assessment in children. Spherical power, Axial Length, Anterior Chamber Depth, Lens Thickness, Photopic Pupil Diameter and Scotopic Pupil Diameter all showed significant progression from pre to post stages, with the average post reading deviating by 0.25 from the normal limits.

The hearing-impaired individuals have communication problems with other hearing people. Sign language helps in bridging the communication gap between a hearing person and hearing-impaired individuals. Thus, it is difficult for the people who use sign language to communicate with others who do not understand it without the use of an interpreter. Sign language interpreters are used to translate spoken language to sign language and vice versa. Main purpose is to provide an efficient way to convert sign language into text., {"references":["1.\tShivashankara, S., & Srinath, S. (2018). American Sign Language recognition system: an optimal approach. International Journal of Image, Graphics and Signal Processing, 11(8), 18.","2.\tTrigueiros, P., Ribeiro, F., & Reis, L. P. (2014). Vision-based Portuguese sign language recognition system. In New Perspectives in Information Systems and Technologies, Volume 1 (pp. 605-617). Springer International Publishing.","3.\tRajan, R. G., & Leo, M. J. (2019). A comprehensive analysis on sign language recognition system. International Journal of Recent Technology and Engineering (IJRTE), 7(6).","4.\tNB, M. K. (2018). Conversion of sign language into text. International Journal of Applied Engineering Research, 13(9), 7154-7161.","5.\tGuo, D., Zhou, W., Li, H., & Wang, M. (2018, April). Hierarchical LSTM for sign language translation. In Proceedings of the AAAI conference on artificial intelligence (Vol. 32, No. 1).","6.\tMurali, R. S. L., Ramayya, L. D., & Santosh, V. A. (2020). Sign language recognition system using convolutional neural network and computer vision.","7.\tSivakumar, P., & Kumar, B. M. (2017). A novel method on earlier detection of bone cancer using Markov random field segmentation. International Journal of Biomedical Engineering and Technology, 23(2-4), 148-158.","8.\tKumar, B. M., Ragaventhiran, J., Bhavana, N., Pandian, M. T., Islabudeen, M., & Sampath, A. K. (2022). Extraction and Recovering of Finger Vein Verification Based on Deep Attribute Representation. Malaysian Journal of Computer Science, 29-42.","9.\tMuthukumar, B., & Ravi, S. (2012). Adaptive Human Motion Estimation Filter with Integrated Phase Compensator. IJCSNS, 12(7), 63.","10.\tNagarathna, C., Kumar, B. M., Bhavana, N., Manjushree, T. L., & Pattan, D. (2022). Improve the Efficiency of Large RFID Network Using Enhanced Security Data Delivery Model for Machine Learning Based Network Intrusion Detection System–A Survey. International Journal of Human Computations & Intelligence, 1(4), 10-17."]}

BackgroundCOVID-19 was declared a global pandemic in March 2020. Early reports were primarily in adults, and sickle cell disease (SCD) was classified as a risk factor for severe COVID-19 disease. However, there are a limited number of primarily multi-center studies reporting on the clinical course of pediatric patients with SCD and COVID-19.MethodsWe conducted an observational study of all patients with SCD diagnosed with COVID-19 at our institution between March 31, 2020, and February 12, 2021. Demographic and clinical characteristics of this group were collected by retrospective chart review.ResultsA total of 55 patients were studied, including 38 children and 17 adolescents. Demographics, acute COVID-19 clinical presentation, respiratory support, laboratory findings, healthcare utilization, and SCD modifying therapies were comparable between the children and adolescents. Seventy-three percent (N = 40) of all patients required emergency department care or hospitalization. While 47% (N = 26) were hospitalized, only 5% (N = 3) of all patients required intensive care unit admission. Patients frequently had concurrent vaso-occlusive pain crisis (VOC) (N = 17, 43%) and acute chest syndrome (ACS) (N = 14, 35%). Those with ACS or an oxygen requirement had significantly higher white blood cell count, lower nadir hemoglobin, and higher D-dimers, supporting a pro-inflammatory and coagulopathic picture. Non-hospitalized patients were more likely to be on hydroxyurea than hospitalized patients (79 vs. 50%, p = 0.023).ConclusionChildren and adolescent patients with SCD and acute COVID-19 often present with ACS and VOC pain requiring hospital-level care. Hydroxyurea treatment appears to be protective. We observed no mortality despite variable morbidity.

Coronary Heart disease is the major factor for people’s deaths throughout the world, and it is necessary to detect and predict the disease in the earlier stages because time plays a vital role to save the coronary patient. From this paper, the authors can conclude that authors have used most of the machine learning and deep learning ensemble algorithms so that it can predict the heart disease at the early stage so that the patient’s life can be saved.

Patients with sickle cell disease (SCD) need frequent health maintenance visits and may face barriers accessing care. Telemedicine, during COVID pandemic, has provided a unique model of care to improve access; however, potential barriers and satisfaction with its use in SCD have not been fully evaluated.To determine caregiver, patient, and healthcare provider (HCP) perspectives and satisfaction with telemedicine in healthcare delivery.We surveyed patients with SCD, caregivers, and HCP, who participated in at least one telemedicine visit from March 2020 to June 2021, using the Telemedicine Usability Questionnaire (TUQ). We also accessed and compared the Press Ganey surveys completed by families who completed a telemedicine or in-person visit. Data were summarized using descriptive statistics. The internal reliability of TUQ was assessed using Cronbach's coefficient alpha. Press Ganey data comparing satisfaction with telemedicine versus in-person visits were analyzed by Mann-Whiney U test.Fifty-two patients/caregivers and 10 HCP completed the survey. Patients/caregivers rated satisfaction "excellent" in the five areas (Usefulness, Ease of use, Effectiveness, Reliability and Satisfaction). HCP rated Usefulness, Ease of use, Effectiveness, Satisfaction as "good," and Reliability as "excellent." Press Ganey scores for satisfaction with care for telemedicine and in-person visits were not statistically different (p .05).We found high satisfaction for caregivers and patients as well as HCP in the delivery of clinical services via telemedicine for SCD. We suggest that telemedicine is a viable option for this population and may help overcome the barriers SCD families often face accessing care.

Hematopoietic stem cell transplantation (HSCT) is potentially curative for patients with sickle cell disease (SCD). Patients with stable donor engraftment after allogeneic HSCT generally do not experience SCD-related complications; however, there are no published data specifically reporting the change in vaso-occlusive events (VOE) after HSCT. Data regarding the number of VOEs requiring medical attention in the 2 years before allogeneic HSCT were compared with the number of VOEs in the 2 years (0-12 months and 12-24 months) after allogeneic HSCT in patients with SCD. One-hundred sixty-three patients with SCD underwent allogeneic HSCT between 2005 and 2019. The average age at the time of HSCT was 21 years (range, 7 months – 64 years). Most patients underwent nonmyeloablative conditioning (75% [N = 123]) and had a matched sibling donor (72% [N = 118]). The mean number of VOEs was reduced from 5.6 (range, 0-52) in the 2 years before HSCT to 0.9 (range, 0-12) in the 2 years after HSCT (P < .001). Among the post-HSCT events, VOE was more frequent during the first 12 months (0.8 [range, 0-12]) than at 12 to 24 months after HSCT (0.1 [range, 0-8) (P < .001)). In patients who had graft rejection (12%, N = 20), VOEs were reduced from 6.6 (range, 0-24) before HSCT to 1.1 (range, 0-6) and 0.8 (range, 0-8) at 0 to 12 months and 12 to 24 months after HSCT, respectively (P < .001). VOEs requiring medical care were significantly reduced after allogeneic HSCT for patients with SCD. These data will inform the development of novel autologous HSCT gene therapy approaches.

Individuals with sickle cell disease (SCD) develop a decline in lung function over time. Hydroxyurea (HU) is the most common disease-modifying therapy used in SCD. We hypothesized that children with SCD treated with HU will have a slower decline in pulmonary function. We performed a retrospective chart review of children with HbSS and HbS-beta zero thalassemia referred to pulmonology for respiratory symptoms. We compared the spirometry results at 2 time points between children on HU (HU group) and not on HU (control group). For the HU group, these endpoints were evaluated before and after being on HU. The mean time interval between 2 spirometry studies was not significantly different between the groups (2.6±1.5 y for HU group vs. 3.0±1.8 y for the control group; P =0.33). The mean age of patients in the HU group was 9.8±3.8 years (55% male) and 10.7±4.9 years (50% male) in the control group. The spirometry data was compared within and between the groups using t test. There was a significant increase in forced vital capacity in HU group during follow-up, while children in the control group showed a decline (7.2±17.1 vs. -3.4±18.2; P0.01). Our study suggests that HU therapy may help preserve lung function over time in children with SCD.

Background Patients with sickle cell disease (SCD) are frequent recipients of red blood cell (RBC) transfusions and are at risk for RBC alloimmunization. RBC alloimmunization is diagnosed by identifying RBC alloantibodies as part of pre-transfusion testing, but this testing fails to detect alloantibodies that have evanesced. It may be beneficial to screen for new RBC alloantibody development after transfusion before possible antibody evanescence. Study design and methods Our institution started a new initiative for episodically transfused patients with SCD to obtain at least one antibody screen 2-6 months after transfusion as part of their clinical care. A database was created to prospectively track all transfused patients for 1 year and their post-transfusion antibody screen results. Patients received prophylactically CEK-matched RBC units. Results During the study year, 138 patients with SCD received a total of 242 RBC transfusions. Patients with a history of an RBC alloantibody (n = 13, 9.4%) had previously received more RBC units than non alloimmunized patients (median 11 vs. 2 RBC units, p = .0002). A total of 337 post-transfusion antibody screens were obtained in 127 patients (92.0%) with 110 patients (79.7%) having at least one antibody screen 2-6 months post-transfusion. With this prospective testing, two new RBC alloantibodies (anti-C and -M) were identified in two patients. Conclusion It is feasible to test for new RBC alloantibody development in most episodically transfused patients with SCD as part of their routine care. The yield of this screening appears low with CEK matching, but it could still provide important information for individual patients.

The study was aimed to find an alternate approach for chemicals used in agriculture to avoid microbial infections. Fungal pathogens cause different types of plant diseases and affect a majority of edible crops by destroying the tissues of the plant in a direct or indirect mechanism. So, an alternative approach led to the development of biocontrol agents using endophytic bacteria. A total of 8 endophytic bacteria were isolated from the root, stem, and leaves of radish (Raphanus sativus). The antagonistic activity of these bacteria against the 2 isolated plant pathogenic fungi was determined in vitro. Two out of eight bacteria showed more than 50% inhibitory activity against one fungus, were further characterized using the 16s rRNA sequencing method. On the basis of the phylogenetic tree of the 16s rRNA method, the endophytic bacterial samples were identified as Tonsilliphilus suis and Exiguobacterium aurantiacum against plant pathogenic Aspergillus flavus isolated from Raphanus sativus, which makes them highly suitable as an alternative for chemical fertilizers to provide resistance to plant pathogenic fungi. The cell wall degrading activities such as protease activity, amylase activity, and plant growth-promoting properties such as Hydrogen cyanide (HCN), Indole acetic acid (IAA), ammonia production of these endophytic bacteria were evaluated. The results show that T. suis is the most effective strain for radish growth development.

The cooling process is an essential aspect while designing for uniform heat transfer between the mold and the molded part. Improper design and placement of cooling channels result in non-uniform cooling and thus results in differential shrinkage and warpage on the final product. The installation of the channels yet plays a crucial role in the cooling of the part. Conforming channels that are placed at an optimum distance from the part to enhance the cooling process. In this paper, the performance parameters of straight drilled channels are compared with the conformal cooling channels for an electric alarm box. The analysis indicates that the conformal cooling method improved and enhanced the cooling process and reduced the defects like warpage and differential shrinkage by 25.5% and 28.0% respectively.

Chronic renal failure or chronic kidney disease is a slowly progressive loss of kidney work over a time of quite a while. As kidney disappointment propels and the organ's capacity is truly weakened, hazardous degrees of waste and liquid can quickly develop in the body. On the off chance that persistent kidney disappointment closes At end-stage kidney infection, the patient won't get by without dialysis or a kidney transplant. Dialysis is adopted for cleaning the blood, is one of the most widely recognized treatment alternatives for patients with the end-stage renal illness. The study aims are to assess the effectiveness of Pranayama on fatigue and insomnia among patients with Hemodialysis. An evaluate approach was used for this study with one group pretest and posttest design. Nonprobability purposive sampling method was used to select the 60 samples of the study. The tool used for this study was fatigue and insomnia severity index was to assess the level of insomnia among patients with Hemodialysis. Pranayama was given to the patients for 15 mins twice a day, one hour after Hemodialysis for 15 days. The collected data were analyzed using descriptive and inferential statistics. The results depicts that mean posttest score of fatigue and insomnia were 19.09 (SD + 8.44), 15.17 (SD+ 4.85) and the mean pretest score were 59.38(SD +8.18), 25.55 (SD+ 3.37) respectively. The mean difference was 40.29 and 10.38, respectively. The paired 't' value were 33.77 and 22.8 and ('t' value= 0.0001) respectively, which was significant at P< 0.05. The above findings showed that Pranayama was an effective intervention in reducing fatigue and insomnia among patients with Hemodialysis.

Early diagnosis, treatment, and prevention of a vaso-occlusive crisis (VOC) are critical to the management of patients with sickle cell disease. It is essential to differentiate between VOC-associated pain and chronic pain, hyperalgesia, neuropathy, and neuropathic pain. The pathophysiology of VOCs includes polymerization of abnormal sickle hemoglobin, inflammation, and adhesion. Hydroxyurea, L-glutamine, crizanlizumab, and voxelotor have been approved by the US Food and Drug Administration for reducing the frequency of VOCs; the European Medicines Agency has approved only hydroxyurea. Other novel treatments are in late-stage clinical development in both the United States and the European Union. The development of agents for prevention and treatment of VOCs should be driven by our understanding of its pathophysiology.

Opioids are a critical component of pain relief strategies for the management of patients with cancer and sickle cell disease. The escalation of opioid addiction and overdose in the United States has led to increased scrutiny of opioid prescribing practices. Multiple reports have revealed that regulatory and coverage policies, intended to curb inappropriate opioid use, have created significant barriers for many patients. The Centers for Disease Control and Prevention, National Comprehensive Cancer Network, and ASCO each publish clinical practice guidelines for the management of chronic pain. A recent JAMA Oncology article highlighted perceived variability in recommendations among these guidelines. In response, leadership from guideline organizations, government representatives, and authors of the original article met to discuss challenges and solutions. The meeting featured remarks by the Commissioner of Food and Drugs, presentations on each clinical practice guideline, an overview of the pain management needs of patients with sickle cell disease, an overview of perceived differences among guidelines, and a discussion of differences and commonalities among the guidelines. The meeting revealed that although each guideline varies in the intended patient population, target audience, and methodology, there is no disagreement among recommendations when applied to the appropriate patient and clinical situation. It was determined that clarification and education are needed regarding the intent, patient population, and scope of each clinical practice guideline, rather than harmonization of guideline recommendations. Clinical practice guidelines can serve as a resource for policymakers and payers to inform policy and coverage determinations.

In the US, mortality in sickle cell disease (SCD) increases after age 18–20 years. Biomarkers of mortality risk can identify patients who need intensive follow-up and early or novel interventions. We prospectively enrolled 510 SCD patients aged 3–20 years into an observational study in 2006–2010 and followed 497 patients for a median of 88 months (range 1–105). We hypothesized that elevated pulmonary artery systolic pressure as reflected in tricuspid regurgitation velocity (TRV) would be associated with mortality. Estimated survival to 18 years was 99% and to 25 years, 94%. Causes of death were known in seven of 10 patients: stroke in four (hemorrhagic two, infarctive one, unspecified one), multiorgan failure one, parvovirus B19 infection one, sudden death one. Baseline TRV ≥2.7 m/second (>2 SD above the mean in age-matched and gender-matched non-SCD controls) was observed in 20.0% of patients who died vs 4.6% of those who survived (P = .012 by the log rank test for equality of survival). The baseline variable most strongly associated with an elevated TRV was a high hemolytic rate. Additional biomarkers associated with mortality were ferritin ≥2000 μg/L (observed in 60% of patients who died vs 7.8% of survivors, P < .001), forced expiratory volume in 1 minute to forced vital capacity ratio (FEV1/FVC)

Objective: Vaginal calculus is an unusual finding. In this study we describe a case of primary vaginal calculus in a rather rare urogenital anomaly- Obstructed hemivagina with ipsilateral renal agenesis (OHVIRA) syndrome. This syndrome is shrouded in controversies. Here we present a mini review about vaginal calculus and theory of embryological development of female genital tract as related to OHVIRA syndrome. Case: A 50 years-old unmarried lady with primary amenorrhoea presented with pain abdomen. She was found to have calculus in the pelvis by x-ray which was thought to be bladder calculus initially. On local examination the vaginal opening was absent. Imaging studies such as NCCT and MRI confirmed that it is a vaginal calculus, located below the uterine cervix, with absent right kidney. She was diagnosed with OHVIRA syndrome with colpolithiasis. On laparotomy she was detected to have unicornuate uterus with absence of right Mullerian structures. The calculus occupied the whole of upper part of vagina, which was a blind pouch. The patient underwent total abdominal hysterectomy, left salpingo-ophorectomy with removal of calculus after opening the vaginal vault. Postoperative recovery was uneventful. Chemical analysis of the calculus revealed calcium magnesium oxalate which is of hematic origin. Keywords: Primary vaginal calculus, Mullerian duct anomaly, Obstructed hemivagina, OHVIRA syndrome, Herlyn-Werner-Wunderlich syndrome.

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

Machine learning is described as a computer program that learns from experience E with regard to some task T and some performance measure P, if its performance on T improves with E as measured by P. Suppose we have a credit card fraud detection which watches which transactions we mark as fraud or not, and on the basis, it knows how to filter better fraudulent transactions then, E is watching your transactions is fraud or not, T is classifying your transactions as fraud or not, P is number of transactions correctly differentiated as spam or not spam. Machine learning has two types: supervised learning and unsupervised learning. Supervised learning is the type of machine learning where machine is provided with input mapped with its output, and these inputs and outputs are used to make a machine learn a particular function from the trained dataset. There are two branches of supervised learning, i.e., classification and regression. In unsupervised learning, we do not supervise model instead we allow machine to work on its own to discover information. Clustering is type of unsupervised learning.

Hematopoietic stem cell transplantation (HSCT) can be curative for sickle cell disease (SCD). SCD patients with cerebrovascular disease are often referred for HSCT. The objective of this study was to describe neurologic outcomes after HSCT in patients with pre-existing SCD and cerebrovascular comorbidity. Patients with SCD treated with HSCT at a single center between 1996 and 2019 were identified. Patients with cerebral ischemia and/or vasculopathy before undergoing HSCT were included. Patients with graft failure were excluded. The cohort was divided into 3 groups: symptomatic stroke, vasculopathy without symptomatic stroke, and isolated silent cerebral infarction (SCI). Magnetic resonance imaging/angiography and neurologic assessments pre- and post-HSCT were analyzed to assess outcomes. In a cohort of 44 patients, there were 25 with symptomatic infarction, 10 with vasculopathy, and 9 with isolated SCI. Post-HSCT ischemic injury (2 symptomatic strokes, 2 SCIs) was identified in 4 patients, all with previous symptomatic infarction. Within this group (n = 25), the post-HSCT incidence of subsequent symptomatic infarction was 1.6 events/100 patient-years, and SCIs occurred at a rate of 2.2 events/100 patient-years. No patient had progression of vasculopathy post-HSCT. Our data show a low incidence of new ischemic injury after successful HSCT for SCD. Patients with a history of both symptomatic stroke and vasculopathy are at greatest risk for post-HSCT ischemic injury.

Psychosocial and affective comorbidities are common in sickle cell disease (SCD) and can strongly influence disease outcomes, especially those related to pain such as frequency and intensity of pain, use of emergency- and hospital-based care and opioid use. Depression, anxiety, sleep disorders, and substance use challenges are among the common comorbidities that inform the patient experience of SCD. Underlying neurocognitive changes may also contribute to the expression of affective disorders in people with SCD. The neurobiological basis of these comorbidities in SCD is being investigated. In this mini-review, we discuss psychosocial and affective disorders that can coexist in children and adults with SCD and highlight how these common psychological pathologies may interact with complications associated with SCD. Patients with SCD should be screened for these comorbidities using standardized screening tools and managed appropriately to improve outcomes.

Pain is the most common symptom experienced by patients with sickle cell disease (SCD) and is associated with poor quality of life. We investigated the association between grey matter volume (GMV) and the frequency of pain crises in the preceding 12 months and SCD-specific quality of life (QOL) assessed by the PedsQLTM SCD module in 38 pediatric patients with SCD. Using voxel-based morphometry methodology, high-resolution T1 structural scans were preprocessed using SPM and further analyzed in SPSS. The whole brain multiple regression analysis identified that perigenual anterior cingulate cortex (ACC) GMV was negatively associated with the frequency of pain crises (r = -0.656, P = 0.003). A two-group t-test analysis showed that the subgroup having pain crisis/crises in the past year also showed significantly lower GMV at left supratemporal gyrus than the group without any pain crisis (p=0.024). The further 21 pain-related regions of interest (ROI) analyses identified a negative correlation between pregenual ACC (r = -0.551, P = 0.001), subgenual ACC (r = -0.540, P = 0.001) and the frequency of pain crises. Additionally, the subgroup with poorer QOL displayed significantly reduced GMV in the parahippocampus (left: P = 0.047; right: P = 0.024). The correlations between the cerebral structural alterations and the accentuated pain experience and QOL suggests a possible role of central mechanisms in SCD pain.

Electrocardiogram (ECG) signals are used to monitor and display heartbeats. However, various forms of proximity noise, such as baseline wander, power line interference (PLI), etc., can corrupt such recordings, causing variations in signal parameters like amplitude and length, which can lead to errors. We propose to compare a notch filter, a FIR filter, and a Least-Mean-Square (LMS) filter to de-noise the ECG signals. The program is written in Xilinx's VLSI toolbox, and we're trying to figure out which filter uses the least amount of power and has the shortest time delay. With this result, we are simulating the particular filter in ModelSim toolbox for filtering the corrupted ECG signal.

Context Painful vaso-occlusive crises (VOCs) associated with sickle cell disease (SCD) are the most common cause of morbidity, hospitalizations, and poor quality of life. Additional symptoms such as sleep disturbances, fatigue, and stress are also common. Non-traditional approaches are often used by families, but concerns remain that patients may forgo standard of care effective therapies in favor of dangerous unproven alternatives. Objectives To describe a single center experience related to a multidisciplinary integrative medicine clinic within the division of hematology dedicated to children and young adults with SCD. Methods The Sickle Cell Integrative Clinic at Children’s National Hospital services patients with SCD. The main goal of this clinic is to provide access to non-pharmacologic interventions, and to manage patients’ symptoms in a holistic manner along with standard of care management of SCD. This IRB approved study evaluated experiences of both patients and parents who attended this clinic. Results Thirty-seven unique patients attended this clinic over 2 years and 31 participated in the study. After attending the SCD integrative clinic, the majority of patients reported integrative therapies to be an acceptable way of treating pain and believed these to be effective. Overall, the vast majority (88 %) of patients reported having a positive experience with the therapies offered in the clinic. None of the patients experienced any adverse events related to integrative therapies provided in the clinic. Conclusion Our experience suggests that encouraging conversations and offering safe and potentially effective integrative therapies alongside conventional SCD therapies under medical guidance allows patients to have an open discussion about their beliefs and treatment goals, improves patient satisfaction and can improve outcomes.

Genetic modifiers of anemia in Plasmodium falciparum infection and sickle cell disease (SCD) are not fully known. Both conditions are associated with oxidative stress, hemolysis and anemia. The CYB5R3 gene encodes cytochrome b5 reductase 3, which converts methemoglobin to hemoglobin through oxidation of NADH. CYB5R3(c.350C > G) encoding CYB5R3(T117S), the most frequent recognized African-specific polymorphism, does not have known functional significance, but its high allele frequency (23% in African Americans) suggests a selection advantage. Glucose-6-phosphate dehydrogenase (G6PD) is essential for protection from oxidants; its African-polymorphic X-linked A+ and A− alleles, and other variants with reduced activity, coincide with endemic malaria distribution, suggesting protection from lethal infection. We examined the association of CYB5R3(c.350C > G) with severe anemia (hemoglobin G) offered protection against severe malarial anemia in children without G6PD deficiency (G6PD wild type or A+/A− heterozygotes) (odds ratio 0.29, P = .022) but not in G6PD A+ or A− hemizygotes/homozygotes. We also examined the relationship of CYB5R3(c.350C > G) with hemoglobin concentration among 267 children and 321 adults and adolescents with SCD in the US and UK and found higher hemoglobin in SCD patients without G6PD deficiency (β = 0.29, P = .022 children; β = 0.33, P = .004 adults). Functional studies in SCD erythrocytes revealed mildly lower activity of native CYB5R3(T117S) compared to wildtype CYB5R3 and higher NADH/NAD+ ratios. In conclusion, CYB5R3(c.350C > G) appears to ameliorate anemia severity in malaria and SCD patients without G6PD deficiency, possibly accounting for CYB5R3(c.350C > G) selection and its high prevalence.

Summary Background India has made substantial progress in improving child survival over the past few decades, but a comprehensive understanding of child mortality trends at disaggregated geographical levels is not available. We present a detailed analysis of subnational trends of child mortality to inform efforts aimed at meeting the India National Health Policy (NHP) and Sustainable Development Goal (SDG) targets for child mortality. Methods We assessed the under-5 mortality rate (U5MR) and neonatal mortality rate (NMR) from 2000 to 2017 in 5 × 5 km grids across India, and for the districts and states of India, using all accessible data from various sources including surveys with subnational geographical information. The 31 states and groups of union territories were categorised into three groups using their Socio-demographic Index (SDI) level, calculated as part of the Global Burden of Diseases, Injuries, and Risk Factors Study on the basis of per-capita income, mean education, and total fertility rate in women younger than 25 years. Inequality between districts within the states was assessed using the coefficient of variation. We projected U5MR and NMR for the states and districts up to 2025 and 2030 on the basis of the trends from 2000 to 2017 and compared these projections with the NHP 2025 and SDG 2030 targets for U5MR (23 deaths and 25 deaths per 1000 livebirths, respectively) and NMR (16 deaths and 12 deaths per 1000 livebirths, respectively). We assessed the causes of child death and the contribution of risk factors to child deaths at the state level. Findings U5MR in India decreased from 83·1 (95% uncertainty interval [UI] 76·7–90·1) in 2000 to 42·4 (36·5–50·0) per 1000 livebirths in 2017, and NMR from 38·0 (34·2–41·6) to 23·5 (20·1–27·8) per 1000 livebirths. U5MR varied 5·7 times between the states of India and 10·5 times between the 723 districts of India in 2017, whereas NMR varied 4·5 times and 8·0 times, respectively. In the low SDI states, 275 (88%) districts had a U5MR of 40 or more per 1000 livebirths and 291 (93%) districts had an NMR of 20 or more per 1000 livebirths in 2017. The annual rate of change from 2010 to 2017 varied among the districts from a 9·02% (95% UI 6·30–11·63) reduction to no significant change for U5MR and from an 8·05% (95% UI 5·34–10·74) reduction to no significant change for NMR. Inequality between districts within the states increased from 2000 to 2017 in 23 of the 31 states for U5MR and in 24 states for NMR, with the largest increases in Odisha and Assam among the low SDI states. If the trends observed up to 2017 were to continue, India would meet the SDG 2030 U5MR target but not the SDG 2030 NMR target or either of the NHP 2025 targets. To reach the SDG 2030 targets individually, 246 (34%) districts for U5MR and 430 (59%) districts for NMR would need a higher rate of improvement than they had up to 2017. For all major causes of under-5 death in India, the death rate decreased between 2000 and 2017, with the highest decline for infectious diseases, intermediate decline for neonatal disorders, and the smallest decline for congenital birth defects, although the magnitude of decline varied widely between the states. Child and maternal malnutrition was the predominant risk factor, to which 68·2% (65·8–70·7) of under-5 deaths and 83·0% (80·6–85·0) of neonatal deaths in India could be attributed in 2017; 10·8% (9·1–12·4) of under-5 deaths could be attributed to unsafe water and sanitation and 8·8% (7·0–10·3) to air pollution. Interpretation India has made gains in child survival, but there are substantial variations between the states in the magnitude and rate of decline in mortality, and even higher variations between the districts of India. Inequality between districts within states has increased for the majority of the states. The district-level trends presented here can provide crucial guidance for targeted efforts needed in India to reduce child mortality to meet the Indian and global child survival targets. District-level mortality trends along with state-level trends in causes of under-5 and neonatal death and the risk factors in this Article provide a comprehensive reference for further planning of child mortality reduction in India. Funding Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.

Opioids are a critical component of pain relief strategies for the management of patients with cancer and sickle cell disease. The escalation of opioid addiction and overdose in the United States has led to increased scrutiny of opioid prescribing practices. Multiple reports have revealed that regulatory and coverage policies, intended to curb inappropriate opioid use, have created significant barriers for many patients. The Centers for Disease Control and Prevention, National Comprehensive Cancer Network, and American Society of Clinical Oncology each publish clinical practice guidelines for the management of chronic pain. A recent JAMA Oncology article highlighted perceived variability in recommendations among these guidelines. In response, leadership from guideline organizations, government representatives, and authors of the original article met to discuss challenges and solutions. The meeting featured remarks by the Commissioner of Food and Drugs, presentations on each clinical practice guideline, an overview of the pain management needs of patients with sickle cell disease, an overview of perceived differences among guidelines, and a discussion of differences and commonalities among the guidelines. The meeting revealed that although each guideline varies in the intended patient population, target audience, and methodology, there is no disagreement among recommendations when applied to the appropriate patient and clinical situation. It was determined that clarification and education are needed regarding the intent, patient population, and scope of each clinical practice guideline, rather than harmonization of guideline recommendations. Clinical practice guidelines can serve as a resource for policymakers and payers to inform policy and coverage determinations.

Meckel’s diverticulum occurs in 2% of the population and is the most common congenital anomaly of the small intestine. It is the only true diverticulum of the small intestine and occurs due to the persistence of a part of the vitello intestinal duct that does not undergo normal obliteration by the fifth to ninth week of gestation. Though the majority are clinically silent, there is a 4-6% lifetime risk of complications. Axial torsion is the rarest complication associated with Meckel’s diverticulum and its coexistence with intestinal obstruction is largely unheard of with reported cases being few and far between. Here we discuss one such case of axial torsion of a giant Meckel’s diverticulum associated with intestinal obstruction in an adult male.

Fournier’s gangrene (FG) is a fulminant and lethal condition usually occurring in the immunocompromised, first described in 1883 by the French dermatologist Jean Alfred Fournier. It is a form of necrotizing fasciitis of the perineal, genitourinary and perianal regions mostly in males with a mortality of nearly 20-50%. It is a surgical emergency and requires early diagnosis aided by scores such as laboratory risk indicator for necrotising fasciitis (LRINEC) and FG severity index (FGSI), extensive debridement combined with supportive procedures to manage associated complications and broad-spectrum antibiotics. Management of FG thus required a multimodal approach and emphasis on reconstruction after recovery in patients who survive was crucial to improving the quality of life in these patients. Here we were presenting 7 cases of FG successfully managed at our institution, grouped under the four methods by which wound closure was achieved: fecal diversion and split skin grafting of scrotum, urinary diversion and penoscrotal split skin grafting, delayed primary closure (with and without orchidectomy) and wound healing by secondary intention.

Microalbuminuria, an early marker of renal injury, may begin early in sickle cell disease (SCD). We conducted a retrospective chart review of 205 patients with SCD. Clinical data and treatment regimens were reviewed. Data were analyzed to determine prevalence and correlates of microalbuminuria and proteinuria. Thirty-one patients (15.2%) had microalbuminuria. Proteinuria, hematuria, age, height, weight, and systolic blood pressure were significantly associated with microalbuminuria. Age was the strongest predictor. We propose that all children with SCD be screened by annual urinalysis and careful blood pressure monitoring at each clinic visit for early identification of children at risk for renal injury.

Inspired by the evolution of biological nervous systems, Neuroevolution (NE) is an approach to Artificial Intelligence (AI) which uses evolutionary algorithms to evolve complex artificial neural networks capable of intelligent behavior. Kenneth O' Stanley et al. proposed an extension of this approach called Neuroevolution of Augmenting Topologies (NEAT) [1], which evolves both topology and parameters. It possesses key features such as complexification, avoiding competing conventions via historical markings, speciation and fitness sharing. Over the years, the performance of NEAT has been improved with better approaches such as HyperNEAT and CoDeepNEAT. Better training methods for NEAT have evolved over the years as well. In this paper, we deduce an analysis of the efficiency and performance of the various algorithms which have been proposed for Topology and Weight Evolving Artificial Neural Networks (TWEANNs). A survey on the existing approaches based on their applications and purpose, along with the various training methods and the challenges incurred has also been discussed. This work will provide learners with a better overview of the past and current research trends in the field of Neuroevolution.