Parallel convolutional processing using an integrated photonic tensor core.

With the proliferation of ultrahigh-speed mobile networks and internet-connected devices, along with the rise of artificial intelligence (AI)1, the world is generating exponentially increasing amounts of data that need to be processed in a fast and efficient way. Highly parallelized, fast and scalable hardware is therefore becoming progressively more important2. Here we demonstrate a computationally specific integrated photonic hardware accelerator (tensor core) that is capable of operating at speeds of trillions of multiply-accumulate operations per second (1012 MAC operations per second or tera-MACs per second). The tensor core can be considered as the optical analogue of an application-specific integrated circuit (ASIC). It achieves parallelized photonic in-memory computing using phase-change-material memory arrays and photonic chip-based optical frequency combs (soliton microcombs3). The computation is reduced to measuring the optical transmission of reconfigurable and non-resonant passive components and can operate at a bandwidth exceeding 14 gigahertz, limited only by the speed of the modulators and photodetectors. Given recent advances in hybrid integration of soliton microcombs at microwave line rates3-5, ultralow-loss silicon nitride waveguides6,7, and high-speed on-chip detectors and modulators, our approach provides a path towards full complementary metal-oxide-semiconductor (CMOS) wafer-scale integration of the photonic tensor core. Although we focus on convolutional processing, more generally our results indicate the potential of integrated photonics for parallel, fast, and efficient computational hardware in data-heavy AI applications such as autonomous driving, live video processing, and next-generation cloud computing services.

Circulating vaccine derived polio virus type 2 outbreak and response in Yemen, 2021-2022, a retrospective descriptive analysis.

BACKGROUND: The outbreaks of circulating Vaccine Derived Polio Viruses (cVDPVs) have emerged as a major challenge for the final stage of polio eradication. In Yemen, an explosive outbreak of cVDPV2 was reported from August 2021 to December 2022. This study aims to compare the patterns of cVDPV2 outbreak, response measures taken by health authorities, and impacts in southern and northern governorates. METHOD: A retrospective descriptive study of confirmed cases of VDPV2 was performed. The data related to cVDPV2 as well as stool specimens and environmental samples that were shipped to WHO-accredited labs were collected by staff of surveillance. Frequencies and percentages were used to characterize and compare the confirmed cases from the southern and northern governorates. The average delayed time as a difference in days between the date of sample collection and lab confirmation was calculated. RESULTS: The cVDPV2 was isolated from 227 AFP cases reported from 19/23 Yemeni governorates and from 83% (39/47) of environmental samples with an average of 7 months delayed from sample collection. However, the non-polio AFP (NPAFP) and adequate stool specimen rates in the north were 6.7 and 87% compared to 6.4 and 87% in the south, 86% (195) and 14%(32) out of the total 227 confirmed cases were detected from northern and southern governorates, respectively. The first and second cases of genetically linked isolates experienced paralysis onset on 30 August and 1st September 2021. They respectively were from Taiz and Marib governorates ruled by southern authorities that started vaccination campaigns as a response in February 2022. Thus, in contrast to 2021, the detected cases in 2022 from the total cases detected in the south were lower accounting for 22% (7 of 32) of compared to 79% (155 of 195) of the total cases the north. CONCLUSION: A new emerging cVDPV2 was confirmed in Yemen. The result of this study highlighted the impact of vaccination campaigns in containing the cVDPV2 outbreak. Maintaining a high level of immunization coverage and switching to nOPV2 instead of tOPV and mOPV2 in campaigns are recommended and environmental surveillance should be expanded in such a risky country.

6-Thioguanine nucleotide levels are associated with infliximab but not adalimumab levels in inflammatory bowel disease patients on combination therapy.

BACKGROUND: Thiopurine co-therapy with anti-tumour necrosis factor-alpha (anti-TNFα) agents is associated with higher anti-TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD). AIMS: We aimed to evaluate the association between 6-thioguanine nucleotide (6-TGN) and anti-TNFα levels and the optimal 6-TGN threshold level associated with higher anti-TNFα levels in combination therapy. METHODS: We performed a retrospective cross-sectional multicentre study of patients with IBD on combination anti-TNFα and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti-TNFα levels. Receiver operator characteristic curves were used to define the optimal 6-TGN cut-off levels associated with therapeutic anti-TNFα levels. RESULTS: The study included 743 paired 6-TGN and anti-TNFα levels (640 infliximab and 103 adalimumab). 6-TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6-TGN cut-off associated with therapeutic infliximab levels (≥5 mcg/mL) was 261 pmol/8 × 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 × 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (≥7.5 mcg/mL), the 6-TGN cut-off was 218.5 pmol/8 × 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 × 108 RBC (AUC = 0.63) for escalated dosing. CONCLUSION: 6-TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6-TGN levels in the lower end of the therapeutic range (230-260 pmol/8 × 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing.

Genome sequencing identifies coding and non-coding variants for non-syndromic hearing loss.

Hearing loss (HL) is a common heterogeneous trait that involves variants in more than 200 genes. In this study, we utilized exome (ES) and genome sequencing (GS) to effectively identify the genetic cause of presumably non-syndromic HL in 322 families from South and West Asia and Latin America. Biallelic GJB2 variants were identified in 58 probands at the time of enrollment these probands were excluded. In addition, upon review of phenotypic findings, 38/322 probands were excluded based on syndromic findings at the time of ascertainment and no further evaluation was performed on those samples. We performed ES as a primary diagnostic tool on one or two affected individuals from 212/226 families. Via ES we detected a total of 78 variants in 30 genes and showed their co-segregation with HL in 71 affected families. Most of the variants were frameshift or missense and affected individuals were either homozygous or compound heterozygous in their respective families. We employed GS as a primary test on a subset of 14 families and a secondary tool on 22 families which were unsolved by ES. Although the cumulative detection rate of causal variants by ES and GS is 40% (89/226), GS alone has led to a molecular diagnosis in 7 of 14 families as the primary tool and 5 of 22 families as the secondary test. GS successfully identified variants present in deep intronic or complex regions not detectable by ES.

Identification and structural characterization of a pathogenic ARSA missense variant in two consanguineous families from Jammu and Kashmir (India) with late infantile metachromatic leukodystrophy.

BACKGROUND: Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder caused by a deficiency of Arylsulfatase A (ARSA) enzyme activity. Its clinical manifestations include progressive motor and cognitive decline. ARSA gene mutations are frequent in MLD. METHODS AND RESULTS: In the present study, whole exome sequencing (WES) was employed to decipher the genetic cause of motor and cognitive decline in proband's of two consanguineous families from J&K (India). Clinical investigations using radiological and biochemical analysis revealed MLD-like features. WES confirmed a pathogenic variant in the ARSA gene. Molecular simulation dynamics was applied for structural characterization of the variant. CONCLUSION: We report the identification of a pathogenic missense variant (c.1174 C > T; p.Arg390Trp) in the ARSA gene in two cases of late infantile MLD from consanguineous families in Jammu and Kashmir, India. Our study utilized genetic analysis and molecular dynamics simulations to identify and investigate the structural consequences of this mutation. The molecular dynamics simulations revealed significant alterations in the structural dynamics, residue interactions, and stability of the ARSA protein harbouring the p.Arg390Trp mutation. These findings provide valuable insights into the molecular mechanisms underlying the pathogenicity of this variant in MLD.

Blind prediction of toluene/water partition coefficients using COSMO-RS: results from the SAMPL9 challenge.

Accurately predicting partition coefficients log P is crucial for reducing costs and accelerating drug design as it provides valuable information about the bioavailability, pharmacokinetics, and toxicity of different drug candidates. However, the performance of the existing methods is ambiguous, making it unclear whether these methods can be effectively utilized in drug discovery. To assess the performance of these methods, a series of SAMPL challenges have been conducted over the past few years, aiming to enable the development and validation of predictive models. In this study, we present two independent contributions to the SAMPL9 challenge for predicting the toluene/water partition coefficients for 16 molecules. Both submissions, A and B, use the COSMO-RS approach, albeit in slightly different procedures, to compute the transfer free energies from water to toluene of the molecules presented in the challenge, and consequently, their corresponding log P values. Based on the results, COSMO-RS submission A achieves the top position with an R2 value of 0.93 while it ranks second in terms of root-mean-square error (RMSE) with a value of 1.23 log P units. COSMO-RS submission B achieves an R2 value of 0.83 and an RMSE value of 1.48 log P units. Following the challenge, we predict the log P values using a neural network model, which was pre-trained on COSMO-RS data achieving an R2 of 0.92 and RMSE of 1.04 log P units. Compared to previous SAMPL challenges, all contributions displayed large deviations in predicting the toluene/water partition coefficient. These large deviations emphasize that further research is needed to develop accurate and reliable methods for modeling solvent effects on small molecule transfer-free energies.

Thyroid autoimmunity and autoimmune thyroid disease in Malaysian girls with Turner syndrome: An understudied population.

AIMS: Knowledge on the spectrum of thyroid disorders amongst Turner syndrome (TS) patients in Southeast Asia is limited. This study aimed to evaluate the prevalence of thyroid autoimmunity, the spectrum of autoimmune thyroid disease and association with age and karyotype amongst Malaysian TS girls. METHODS: A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records. RESULTS: Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood. CONCLUSION: Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.

An outbreak of SARS-CoV-2 in a public-facing office in England.

BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an attack rate of 55% (22/40 workers) occurred at a public-facing office in England from August to September 2021. Published evidence regarding outbreaks in office workplaces remains limited. AIMS: To describe an investigation of workplace- and worker-related risk factors following an outbreak of SARS-CoV-2 in a public-facing office. METHODS: The COVID-19 (coronavirus disease 2019) Outbreak Investigation to Understand Transmission (COVID-OUT) study undertook an investigation of the outbreak. This included surface sampling, occupational environmental assessment, molecular and serological testing of workers, and detailed questionnaires. RESULTS: Despite existing COVID-19 control measures, surface sampling conducted during a self-imposed 2-week temporary office closure identified viral contamination (10/60 samples, 17% positive), particularly in a small, shared security office (6/9, 67% positive) and on a window handle in one open-plan office. Targeted enhanced cleaning was, therefore, undertaken before the office reopened. Repeat surface sampling after this identified only one positive (2%) sample. Ventilation was deemed adequate using carbon dioxide monitoring (typically ≤1000 ppm). Twelve workers (30%) responded to the COVID-OUT questionnaire, and all had been vaccinated with two doses. One-third of respondents (4/12) reported direct physical or close contact with members of the public; of these, 75% (3/4) reported a divider/screen between themselves and members of the public. CONCLUSIONS: The results highlight the potential utility of surface sampling to identify SARS-CoV-2 control deficiencies and the importance of evolving, site-specific risk assessments with layered COVID-19 mitigation strategies.

Factors influencing time management skills among nurses in North West Bank, Palestine.

BACKGROUND: In today's companies, time management abilities have grown as a significant predictor of nurses' success. Organizations have simplified their internal operations and flattened their organizational structures in an effort to increase productivity and cut expenses. As a result, successful time management skills are particularly crucial for nurses in recently restructured healthcare organizations. This study aimed at exploring factors influencing time management skills among Palestinian nurses. METHODS: Cross-sectional quantitative study of all nurses (715) working in private and government hospitals and primary healthcare centers in north Palestine was conducted. Time management skills were measured on a continuous scale using the Nursing Time Management Scale (NTMS), Arabic version. The scale measures various aspects of time management including goal setting, planning, scheduling, and organizing activities. The relationship between time management skills and background variables was assessed using the multivariate linear regression. RESULTS: The average total score for NTMS scale was 63.39 out of a total score of 90. This score indicates relatively good time management skills among the respondents. The multivariate linear regression results showed that females obtained slightly lower scores than males, coefficient = -2.36, p = 0.043. Nurses in primary care centers had significantly higher scores than nurses who work at hospitals, coefficient = 4.47, p = 0.004. The type of healthcare organization emerged as a significant factor predicting time management skills. Nurses in private hospitals had worse time management skills than nurses in government hospitals, coefficient = -12.27, p < 0.001. Nurse supervisors had better time management skills than staff nurses, coefficient = 4.01, p = 0.023. Nurses working in non-teaching hospitals had worse time management skills than nurses in teaching hospitals, coefficient = - 3.86, p = 0.001. Nurses who did not attend a time management course had worse time management skills than nurses who attended time management course, coefficient = - 4.05, p = p < 0.001. CONCLUSIONS: Healthcare institutions should consider organizational and individual factors to improve the time management skills of their staff. Time management training interventions are proven and effective policies that are recommended to be adopted by all healthcare centers.

Psychometric properties of Nursing Time Management Scale (NTMS), Arabic version.

Despite the presence of numerous generic time management instruments, relatively few research articles have assessed the validity and reliability of time management skills specific for the nursing profession. This study aimed at developing and validating a time management scale for nurses.Method A self-administered questionnaire was administered to 715 nurses working in hospitals and clinics in the northern region of the West Bank, Palestine. The scale was examined through exploratory factor analysis, reliability measures, and correlations with other scales.Results The scale revealed a 3-factor structure 1) organization of nursing work 2) planning and goal setting and 3) coordination of nursing work. The scale demonstrated excellent psychometric properties.Conclusions The Nursing Time Management Scale (NTMS) is a valid and reliable measure that can be used in assessing time management skills of nurses and in evaluating interventions and training modules aiming at developing nurses' time management skills.

Characterization of infectious laryngotracheitis virus isolates from laying hens during 2019-2020 outbreaks in Tamil Nadu, India.

Infectious laryngotracheitis (ILT) is an acute respiratory disease in chickens that is a serious threat to poultry-producing countries worldwide. In the present study, we isolated and characterized infectious laryngotracheitis (ILTV) virus isolates by sequencing and restriction fragment length polymorphism analysis of PCR-amplified products (PCR-RFLP). A total of 26 ILTV outbreaks were investigated that occurred between 2019 and 2020 in flocks that had not been vaccinated against ILTV. ILTV was isolated by cultivating tracheal samples in embryonated chicken eggs, which showed multiple opaque pock lesions and thickening of the chorioallantoic membrane after 120 hours of infection. The ILTV isolates were identified and characterized by PCR and sequencing a portion of the ICP4 and TK genes. Phylogenetic analysis based on the ICP4 region showed that the sequences clustered with chicken-embryo-origin vaccine-like strains. Sequence analysis of the ICP4 region differentiated chicken-embryo-origin (CEO), tissue-culture-origin (TCO), and field ILTV strains, with significant differences in nucleotide and amino acid sequences. Furthermore, PCR-RFLP analysis of the TK gene showed that the patterns were identical to those obtained with low-virulence and vaccine strains. In conclusion, sequencing of a portion of the ICP4 region of ILTV allowed differentiation of ILTV field, CEO, and TCO vaccine strains. In this study, CEO-vaccine-like strains were found to be the cause of ILTV outbreaks between 2019 and 2020 in Tamil Nadu in southern India.

Enhancing the photocatalytic performance of surface - Treated SnO2 hierarchical nanorods against methylene blue dye under solar irradiation and biological degradation.

Surfactant -treated tin oxide (SnO2) hierarchical nanorods were successfully synthesized through hydrothermal technique. The X-ray diffraction analysis showed the prepared SnO2 possesses tetragonal rutile structure having appreciable crystallinity with crystallite sizes in the range of 110 nm-120 nm. UV-visible diffuse reflectance absorption spectra confirm that the better visible light absorption band of SnO2 hierarchical nanorods have red shift compared to the pure SnO2. Fourier transform infrared spectroscopy (FTIR) study evident that the as-prepared SnO2 nanorods encompass the characteristic bands of SnO2 nanostructures. The morphological analyses of prepared materials were performed by FESEM, which shows that hierarchal nanorods and complex nanostructures. EDX analyses disclose all the samples are composed of Sn and O elements. The photocatalytic performance of the prepared surfactant treated SnO2 hierarchical nanorods was evaluated using methylene blue (MB) dye removal under direct natural sunlight. Recycling experiment results of CTAB - SnO2 nanorods and photocatalytic reaction mechanism also discussed in detail.

Effect of Ag doped MnO2 nanostructures suitable for wastewater treatment and other environmental pollutant applications.

A modest sol-gel method has been employed to prepare the pure and Ag doped MnO2 nanoparticles and methodologically studied their physical, morphological, and photosensitive properties through XRD, TEM, EDAX, Raman, UV, PL and N2 adsorption - desorption study. Tetragonal crystalline arrangement with spherical nanoparticles was found out through XRD and TEM studies. The EDAX studies further supported that formation Ag in the MnO2 crystal matrix. The bandgap energy of Ag doped MnO2 was absorbed through UV spectra. Photo -generated recombination process and surface related defects were further recognized by PL spectra. Through visible light irradiation, the photo - degradation of methyl orange (MO) and phenol dye solutions were observed. The optimum condition of (10 wt% of Ag) Ag doped MnO2 catalyst showed tremendous photocatalytic efficiency towards MO than phenol under same experimental study.

Photocatalytic degradation effect of CdSe nanoparticles for textile wastewater effluents at low cost and proves to be efficient method.

Semiconductor nanoparticles and nanocrystals have a great impact due to its contribution in the diverse fields including electronics, solar energy, biological imaging, and photonics. Among these semiconductor nanoparticles, cadmium selenide of II-VI group binary semiconductor nanoparticles were synthesized using solvothermal process for the different reaction temperatures. The XRD pattern of the synthesized samples confirms the crystalline nature of the samples and showed increase in its crystallite size with rise in temperature. The morphology of the samples was analysed with TEM images and found that the nanoparticles synthesized at different temperatures were varied in size and shape indicating the increase in the size of the particles with the raise in temperature. The optical properties of the samples pointed out that they exhibit a blue shift owing to quantum confinement. Photocatalytic activity was carried out for the synthesized samples under visible light radiation using methylene blue (MB) as a model pollutant and it proved to be a good photocatalyst achieving the efficiency of 75% which is promising for future application with good optimization. The efficiency could be increased when these semiconductor CdSe nanoparticles are doped with metal particles due to an increase in the absorption edge wavelength and a decrease in bandgap energy were reported in detail.

3D CoMoO4 nanoflake arrays decorated disposable pencil graphite electrode for selective and sensitive enzyme-less electrochemical glucose sensors.

Three-dimensional (3D) cobalt molybdate (CoMoO4) hierarchical nanoflake arrays on pencil graphite electrode (PGE) (CoMoO4/PGE) are actualized via one-pot hydrothermal technique. The morphological features comprehend that the CoMoO4 nanoflake arrays expose the 3D, open, porous, and interconnected network architectures on PGE. The formation and growth mechanisms of CoMoO4 nanostructures on PGE are supported with different structural and morphological characterizations. The constructed CoMoO4/PGE is operated as an electrocatalytic probe in enzyme-less electrochemical glucose sensor (ELEGS), confronting the impairments of cost- and time-obsessed conventional electrode polishing and catalyst amendment progressions and obliged the employment of a non-conducting binder. The wide-opened interior and exterior architectures of CoMoO4 nanoflake arrays escalate the glucose utilization efficacy, whilst the intertwined nanoflakes and graphitic carbon layers, respectively, of CoMoO4 and PGE articulate the continual electron mobility and catalytically active channels of CoMoO4/PGE. It jointly escalates the ELEGS concerts of CoMoO4/PGE including high sensitivity (1613 µA mM-1 cm-2), wide linear glucose range (0.0003-10 mM), and low detection limit (0.12 µM) at a working potential of 0.65 V (vs. Ag/AgCl) together with the good recovery in human serum. Thus, the fabricated CoMoO4/PGE extends exclusive virtues of modest electrode production, virtuous affinity, swift response, and excellent sensitivity and selectivity, exposing innovative prospects to reconnoitring the economically viable ELEGSs with binder-free, affordable cost, and expansible 3D electrocatalytic probes.

Foetal alcohol spectrum disorder and Investigative interviewing: A systematic review highlighting clinical and legal implications and recommendations.

Individuals with foetal alcohol spectrum disorders (FASD) are estimated to be 19 times more likely to encounter the criminal justice system (CJS) in comparison to individuals without FASD. During encounters with the CJS, investigative interviews are employed to obtain accurate information from suspects, victims or witnesses of crime. A systematic search using PRISMA guidelines was performed to identify empirical studies published that have explored the questioning of the FASD population within the CJS and the vulnerabilities of FASD-impacted individuals during investigative interviewing. A total of 383 studies were identified from the databases searched and 7 further studies were identified from Google Scholar. After deduplication, abstract and title screening, the full text of 23 studies were assessed for inclusion and 5 were included in the narrative synthesis of results. Two papers were empirical studies focussed on the performance of FASD-impacted individuals during investigative interviewing. Whilst the first study found the FASD population susceptible to suggestions, the second (a case study), identified the ploys employed during investigative interviewing to obtain a confession. Three papers studied the wider vulnerabilities of FASD-impacted individuals and found diminished psycho-legal abilities, increased risk of recidivism and biological, psychological and social factors that render FASD-impacted individuals vulnerable to CJS encounters. Despite the greater likelihood of CJS encounters, the result of this review highlights the slim evidence base useful to establish the vulnerabilities of FASD-impacted individuals within the CJS.

Prevalence of fetal alcohol spectrum disorder in Greater Manchester, UK: An active case ascertainment study.

BACKGROUND: Despite high levels of prenatal alcohol exposure in the UK, evidence on the prevalence of fetal alcohol spectrum disorders (FASD) is lacking. This paper reports on FASD prevalence in a small sample of children in primary school. METHODS: A 2-phase active case ascertainment study was conducted in 3 mainstream primary schools in Greater Manchester, UK. Schools were located in areas that ranged from relatively deprived to relatively affluent. Initial screening of children aged 8-9 years used prespecified criteria for elevated FASD risk (small for age; special educational needs; currently/previously in care; significant social/emotional/mental health symptoms). Screen-positive children were invited for detailed ascertainment of FASD using gold standard measures that included medical history, facial dysmorphology, neurological impairment, executive function, and behavioral difficulties. RESULTS: Of 220 eligible children, 50 (23%) screened positive and 12% (26/220) proceeded to Phase 2 assessment. Twenty had a developmental disorder, of whom 4 had FASD and 4 were assessed as possible FASD. The crude prevalence rate of FASD in these schools was 1.8% (95% CI: 1.0%, 3.4%) and when including possible cases was 3.6% (2.1%, 6.3%). None of these children had previously been identified with a developmental diagnosis. CONCLUSIONS: FASD was found to be common in these schools and most of these children's needs had not previously been identified. A larger, more definitive study that uses a random sampling technique stratified by deprivation level to select schools is needed to make inferences regarding the population prevalence of FASD.

Uniting the Global Gastroenterology Community to Meet the Challenge of Climate Change and Nonrecyclable Waste.

Climate change has been described as the greatest public health threat of the 21st century. It has significant implications for digestive health. A multinational team with representation from all continents, excluding Antarctica and covering 18 countries, has formulated a commentary which outlines both the implications for digestive health and ways in which this challenge can be faced.

Giant axonal neuropathy with novel GAN pathogenic variant in a patient of consanguineous origin from Poonch Jammu and Kashmir-India.

Giant axonal neuropathy (GAN) is a severe and rare autosomal recessive neurodegenerative disorder of childhood affecting both the peripheral and central nervous systems (CNS). It is caused by mutations in the GAN (gigaxonin) gene linked to chromosome 16q24. Here, we present a 15-year-old male patient with GAN from a consanguineous family of Poonch, Jammu and Kashmir (J&K)-India. Whole-exome sequencing (WES) was employed to unravel the genetic cause of GAN in the proband. Pathogenic variant identified with WES was confirmed in other affected sibling using Sanger sequencing. Magnetic resonance imaging (MRI) and detailed clinical investigation was also carried out on proband. WES revealed a novel homozygous stopgain GAN mutation (NM_022041, c.C1028G, p.S343X) in the patient. MRI of brain displayed bilateral symmetrical confluent areas of deep white matter signal changes affecting periventricular regions (with sparing of subcortical U-fibers), posterior limbs of internal capsules, thalami, external capsules, and semioval centers. The patient was initially suspected to be a case of metachromatic leukodystrophy. However, WES analysis revealed a pathogenic variant in GAN gene as causative. No other pathogenic variant relevant to any other type of dystrophy was reported in WES. Our findings extend the geographical distribution of GAN to even a very remote region in India, extend the mutational and imaging spectrum of GAN and substantiate the need for introducing genetic testing and counselling in primary referral centers/district hospitals in India.