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Purpose. Visual loss is a devastating perioperative complication that can result from elevated intraocular pressure (IOP). The Trendelenburg position during surgery increases IOP. The purpose of this study was to quantify IOP changes in patients undergoing laparoscopic hysterectomy, at different time points and body positions throughout the procedure, and to compare fluctuations of IOP during the perioperative period according to two fluid management protocols. Methods. Thirty women scheduled to undergo elective gynecologic laparoscopic pelvic surgery were randomly allocated to receive a liberal or restrictive fluid management protocol. IOP, mean arterial pressure, heart rate, exhaled tidal volume, end-tidal CO2, and ocular perfusion pressure were assessed prior, during, and postsurgery, at 8 time points altogether. Results. Mean changes in IOP were similar for the two protocols; the peak IOP was at the steep (peak) Trendelenburg position. For each protocol, IOP correlated positively with mean arterial pressure, and mean blood pressure correlated with ocular perfusion pressure. Conclusion. IOP was elevated during laparoscopic pelvic surgery and particularly at the steep Trendelenburg position. No differences were found in any of the parameters examined according to a liberal or restrictive fluid management protocol.

PurposeConstitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals.Patients and methodsData were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation.ResultsA total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years.ConclusionSurveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

Abstract Psychological resilience, the ability to adapt to adversity, is theorized to rely on intact inhibitory control (IC) mechanisms, which underlie one’s ability to maintain goal-directed behavior by inhibiting prepotent responses. However, no study to date has explored daily fluctuations of IC performance in relation to resilience. Here, we examined the association between IC and mood measured daily in relation to psychological resilience in young adults in a stressful situation. Baseline resilience was obtained from 144 female and male soldiers during their basic combat training. Then, participants completed an ecological momentary assessment protocol, in which they reported their momentary mood and completed a short IC assessment twice/day for 2 weeks. A hierarchical linear modeling analysis revealed that psychological resilience moderated the relationship between momentary IC and momentary mood, such that better IC was associated with better mood only for those with higher, but not lower, self-reported psychological resilience at baseline. These results show that psychological resilience is manifested in the everyday association between IC and mood. Furthermore, they lend important support to cognitive models of resilience and may have significant contribution to our understanding of resilient behavior in real life. Trial Registration: MOH_2018-0-13_002451.

Abstract Squamous cell carcinoma antigen recognized by T cells 3 (SART3) is an RNA-binding protein with numerous biological functions including recycling small nuclear RNAs to the spliceosome. Here, we identify recessive variants in SART3 in nine individuals presenting with intellectual disability, global developmental delay and a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Knockdown of the Drosophila orthologue of SART3 reveals a conserved role in testicular and neuronal development. Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro. Collectively, these findings suggest that bi-allelic SART3 variants underlie a spliceosomopathy which we tentatively propose be termed INDYGON syndrome (Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XY GONadal dysgenesis). Our findings will enable additional diagnoses and improved outcomes for individuals born with this condition.

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical and molecular spectrum of WSS in diverse populations, to identify physical features that may be more prevalent in White versus Black Indigenous People of Color individuals, to delineate genotype-phenotype correlations, to define developmental milestones, to describe the syndrome through adulthood, and to examine clinicians' differential diagnoses. Sixty-nine of the 82 variants (84%) observed in the study were not previously reported in the literature. Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%). The median ages at walking and first words were 20 months and 18 months, respectively. Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non-LoF variants. This study identifies genotype-phenotype correlations as well as race-facial feature associations in an ethnically diverse cohort, and accurately defines developmental trajectories, medical comorbidities, and long-term outcomes in individuals with WSS.

Dengue is the most prevalent arboviral disease worldwide, and the four dengue virus (DENV) serotypes circulate endemically in many tropical and subtropical regions. Numerous studies have shown that the majority of DENV infections are inapparent, and that the ratio of inapparent to symptomatic infections (I/S) fluctuates substantially year-to-year. For example, in the ongoing Pediatric Dengue Cohort Study (PDCS) in Nicaragua, which was established in 2004, the I/S ratio has varied from 16.5:1 in 2006-2007 to 1.2:1 in 2009-2010. However, the mechanisms explaining these large fluctuations are not well understood. We hypothesized that in dengue-endemic areas, frequent boosting (i.e., exposures to DENV that do not lead to extensive viremia and result in a less than fourfold rise in antibody titers) of the immune response can be protective against symptomatic disease, and this can explain fluctuating I/S ratios. We formulate mechanistic epidemiologic models to examine the epidemiologic effects of protective homologous and heterologous boosting of the antibody response in preventing subsequent symptomatic DENV infection. We show that models that include frequent boosts that protect against symptomatic disease can recover the fluctuations in the I/S ratio that we observe, whereas a classic model without boosting cannot. Furthermore, we show that a boosting model can recover the inverse relationship between the number of symptomatic cases and the I/S ratio observed in the PDCS. These results highlight the importance of robust dengue control efforts, as intermediate dengue control may have the potential to decrease the protective effects of boosting.

Indoor Localization is gaining increased importance due to numerous location-based services in healthcare, logistics, and security, to name few, that are expected to be provided by next-generation wireless networks. Such services are characterized by stringent accuracy requirements, short response time, and lower cost which makes the localization problem more challenging and deserving of attention. A key element of the localization process is distance estimation (also known as ranging). In this paper, we design and analyze an efficient decimeter-level two-way ranging scheme for ubiquitous WiFi networks in the 5 GHz frequency band whose accuracy approaches ideal one-way ranging with no phase mismatches. We investigate the idea of channel frequency response (CFR) stitching across non-contiguous WiFi channels and how two-way CFR measurements help in achieving the CFR coherency necessary for accurate ranging. In addition, we quantify the decrease in ranging accuracy of two-way compared to one-way ranging due to SNR degradation, Line-of-Sight (LoS) component shrinkage, and doubling the multipath delay spread. Furthermore, We design a novel scheme to bridge the performance gap between two-way ranging and ideal one-way ranging which operates in three main steps: square-root of the two-way CFR, followed by phase unwrapping, and finally deep fade detection and phase errors correction. Our proposed scheme achieves significant performance gains over two-way ranging with only a slight performance gap from ideal one-way ranging. Moreover, our proposed scheme enjoys robustness as it preserves the ranging accuracy gains in various WiFi communication scenarios when operating at different SNR levels, different multipath channel models, and different CFR bandwidths, as well as operating under system impairments such as Sample Timing Offset (STO). The accuracy gains achieved by the proposed schemes are demonstrated using both simulations and an in-house WiFi testbed. Finally, we quantify the added complexity of our proposed scheme and show it to be insignificant compared to that of the MUSIC super-resolution ranging steps which confirms the practical viability of our proposed scheme.

The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen-activated protein kinase (MAPK) pathway. The RASopathies include NF1, Noonan syndrome, Noonan syndrome with multiple lentigines, Costello syndrome, cardio-facio-cutaneous syndrome, Legius syndrome, capillary malformation arterio-venous malformation syndrome, and SYNGAP1 autism. Due to their common underlying pathogenetic etiology, all these syndromes have significant phenotypic overlap of which one common feature include a predisposition to tumors, which may be benign or malignant. Together as a group, they represent one of the most common multiple congenital anomaly syndromes estimating to affect approximately one in 1000 individuals worldwide. The subcontinent of India represents one of the largest populations in the world, yet remains underserved from an aspect of clinical genetics services. In an effort to bridge this gap, the First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and Advances of New Therapeutics was held in Kochi, Kerala, India. These proceedings chronicle this timely and topical international symposium directed at discussing the best practices and therapies for individuals with neurofibromatoses and RASopathies.

Measurement(s) Picture naming norms • Picture familiarity ratings Technology Type(s) Online experiment

Representations of the fingers are embodied in our cognition and influence performance in enumeration tasks. Among deaf signers, the fingers also serve as a tool for communication in sign language. Previous studies in normal hearing (NH) participants showed effects of embodiment (i.e., embodied numerosity) on tactile enumeration using the fingers of one hand. In this research, we examined the influence of extensive visuo-manual use on tactile enumeration among the deaf. We carried out four enumeration task experiments, using 1-5 stimuli, on a profoundly deaf group (n = 16) and a matching NH group (n = 15): (a) tactile enumeration using one hand, (b) tactile enumeration using two hands, (c) visual enumeration of finger signs, and (d) visual enumeration of dots. In the tactile tasks, we found salient embodied effects in the deaf group compared to the NH group. In the visual enumeration of finger signs task, we controlled the meanings of the stimuli presentation type (e.g., finger-counting habit, fingerspelled letters, both or neither). Interestingly, when comparing fingerspelled letters to neutrals (i.e., not letters or numerical finger-counting signs), an inhibition pattern was observed among the deaf. The findings uncover the influence of rich visuo-manual experiences and language on embodied representations. In addition, we propose that these influences can partially account for the lag in mathematical competencies in the deaf compared to NH peers. Lastly, we further discuss how our findings support a contemporary model for mental numerical representations and finger-counting habits.

Dengue virus (DENV) is the most prevalent human vector-borne viral disease. The force of infection (FoI), the rate at which susceptible individuals are infected in a population, is an important metric for infectious disease modeling. Understanding how and why the FoI of DENV changes over time is critical for developing immunization and vector control policies. We used age-stratified seroprevalence data from 12 years of the Pediatric Dengue Cohort Study in Nicaragua to estimate the annual FoI of DENV from 1994 to 2015. Seroprevalence data revealed a change in the rate at which children acquire DENV-specific immunity: in 2004, 50% of children age >4 years were seropositive, but by 2015, 50% seropositivity was reached only by age 11 years. We estimated a spike in the FoI in 1997-1998 and 1998-1999 and a gradual decline thereafter, and children age

Interhemispheric functional connectivity abnormalities are often reported in autism and it is thus not surprising that structural defects of the corpus callosum (CC) are consistently found using both traditional MRI and DTI techniques. Past DTI studies however, have subdivided the CC into 2 or 3 segments without regard for where fibers may project to within the cortex, thus placing limitations on our ability to understand the nature, timing and neurobehavioral impact of early CC abnormalities in autism. Leveraging a unique cohort of 97 toddlers (68 autism; 29 typical) we utilized a novel technique that identified seven CC tracts according to their cortical projections. Results revealed that younger (