Multimeric single-domain antibody complexes protect against bunyavirus infections.

The World Health Organization has included three bunyaviruses posing an increasing threat to human health on the Blueprint list of viruses likely to cause major epidemics and for which no, or insufficient countermeasures exist. Here, we describe a broadly applicable strategy, based on llama-derived single-domain antibodies (VHHs), for the development of bunyavirus biotherapeutics. The method was validated using the zoonotic Rift Valley fever virus (RVFV) and Schmallenberg virus (SBV), an emerging pathogen of ruminants, as model pathogens. VHH building blocks were assembled into highly potent neutralizing complexes using bacterial superglue technology. The multimeric complexes were shown to reduce and prevent virus-induced morbidity and mortality in mice upon prophylactic administration. Bispecific molecules engineered to present two different VHHs fused to an Fc domain were further shown to be effective upon therapeutic administration. The presented VHH-based technology holds great promise for the development of bunyavirus antiviral therapies.

Transmission Properties of FeCl3-Intercalated Graphene and WS2 Thin Films for Terahertz Time-Domain Spectroscopy Applications.

Time-resolved terahertz spectroscopy has become a common method both for fundamental and applied studies focused on improving the quality of human life. However, the issue of finding materials applicable in these systems is still relevant. One of the appropriate solution is 2D materials. Here, we demonstrate the transmission properties of unique graphene-based structures with iron trichloride FeCl3 dopant on glass, sapphire and Kapton polyimide film substrates that previously were not investigated in the framework of the above-described problems in near infrared and THz ranges. We also show properties of a thin tungsten disulfide WS2 film fabricated from liquid crystal solutions transferred to a polyimide and polyethylene terephthalate substrates. The introduction of impurities, the selection of structural dimensions and the use of an appropriate substrate for modified 2D layered materials allow to control the transmission of samples for both the terahertz and infrared ranges, which can be used for creation of effective modulators and components for THz spectroscopy systems.

Inter-rater reliability of distal ureteral diameter ratio compared to grade of VUR.

INTRODUCTION AND OBJECTIVE: Management of vesicoureteral reflux (VUR) remains controversial, and reflux grade constitutes an important prognostic factor. Recent work has suggested that distal ureteral diameter ratio (UDR) is a predictive factor relative to clinical outcome independent of grade. Previous studies have noted significant inter-rater variability with grading of VUR. The present study compared inter-rater reliability of reflux grade and UDR in children with primary VUR. STUDY DESIGN: Four pediatric urologists independently reviewed, in a blinded fashion, voiding cystourethrograms. For each renal unit, grade was assigned according to the standardized international scale. The UDR was calculated by dividing the largest ureteral diameter within the false pelvis by the distance between L1-L3 vertebral bodies. Correlation within each rater was determined using Pearson's correlation coefficient. Reliability of VUR grade and UDR were calculated using two-way ANOVA model inter-rater agreement. RESULTS: Four independent raters reliably measured VUR grade (ICC = 0.87, 95% CI = 0.78-0.93) and UDR (ICC = 0.95, 95% CI = 0.92-0.97). While UDR and grade were equally reliable measures, UDR had a tighter confidence interval. For each rater, grade and UDR were well correlated (r = 0.73-0.84; P < 0.0001). For higher-grade reflux, grade was more variable than UDR (Summary Figure). Using empirical thresholds, the increased variability of grade compared with UDR may lead to significant differences in clinical decision-making among physicians (P = 0.022). DISCUSSION: Known discordance with grading reflux emphasizes the need for a more objective VUR measurement, as clinicians and parents often opt for clinical intervention based on both clinical course and the likelihood of spontaneous resolution. While ICC for UDR and grade were not significantly different, the confidence intervals for grade were wider due to greater variability among grade measurements. This suggests that using UDR measurements may lead to more accurate characterization of VUR and ultimately more consistent clinical decision-making across providers. CONCLUSIONS: Ureteral diameter ratio has good inter-rater reliability among pediatric urologists, with less clinically relevant variability than VUR grade. Ureteral diameter ratio is a more objective and reliable measure than grade, and may be more useful in clinical decision-making.

Military Occupations Most Affected by Head/Sensory Injuries and the Potential Job Impact of Those Injuries.

OBJECTIVE: Identifying Department of Defense (DoD) occupations affected by injuries to the head and sensory systems. METHODS: We explored the Defense Medical Epidemiology Database to identify occupations with the highest incidence of injured personnel, then ranked how frequently they occurred in a top 10 list for each of four injury categories (head/brain, visual, auditory, vestibular) encompassing 25 injury codes. Across all four categories, the most affected occupations were identified, among which we chose three Army combat-related military occupational specialties (MOSs) for detailed study. We identified skills needed to perform these MOSs and explored whether MOS-critical deficits could be expected following the injuries. RESULTS: Some DoD occupations are more likely to suffer from these injuries, including Infantry, Combat Operations Control, Artillery/Gunnery, Motor Vehicle Operator, Combat Engineering, and Armor/Amphibious. Within these DoD occupations, we explored three Army combatant MOSs: Infantry (11B), Cavalry Scout (19D), and Artillery (13B), confirming that these jobs are likely to be disrupted by injuries within the four categories. CONCLUSIONS: Head and sensory injuries disproportionately affect certain military occupations. Relatively few injuries disrupt combat-related abilities that are job critical (e.g., firearms operation) and job specific (e.g., Artillery gunnery problems); these should be the focus of efforts to improve rehabilitation and RTD outcomes.

Utility of the distal ureteral diameter on VCUG for grading VUR.

INTRODUCTION: For children with VUR the grade of vesicoureteral reflux (VUR) remains one of the most predictive factors relative to outcome. However, the subjective nature of the currently accepted international reflux grading system (IRGS) leads to inter-observer variation. The potential of a direct measurement of the distal ureter on the voiding cystourethrogram (VCUG) normalized to the L1-L3 vertebral body distance (ureteral diameter ratio - UDR) to augment the ability of IRGS to predict the ultimate clinical outcome has previously been reported in a group of 79 children. OBJECTIVE: The goal of this current review was to expand the previous review and analysis in order to assess the predictive ability of the UDR with respect to earlier clinical outcome and to compare this ability to the grade of VUR while controlling for other variables. STUDY DESIGN: This retrospective review of the VCUG of 157 children with primary VUR included 124 girls and 33 boys with a mean age of 2.7 years (7 days-13.5 years). In addition to the UDR, other variables that were analyzed included: age, gender, VUR grade, laterality, history of febrile urinary tract infection (UTI) or multiple UTIs prior to diagnosis, and bladder-bowel dysfunction (BBD). Cox regression analysis was utilized and a generalized logit model for 2-year outcome was also fitted to compare the effect of UDR and VUR grade using Wald Chi-squared analysis. RESULTS: The 2-year outcome after the VCUG was defined as: persistent VUR (47%), spontaneous VUR resolution (15%), or operative intervention (38%). Reasons for operative intervention included: breakthrough UTI (1/3), decreased relative renal function associated with renal scarring (1/3), and failure to resolve, along with parental preference (1/3). Increasing UDR was significantly associated with increased grade and a decreased chance of spontaneous resolution. It was unlikely for a child with Grade 4, 3, or 2 VUR to have spontaneous resolution if their UDR was above 0.25, 0.3, or 0.35, respectively. In addition, higher grades of VUR, older age, and bilateral VUR were significantly associated with failure to spontaneously resolve VUR. As seen in Figure, children with grades 2 and 3 VUR less than 2 years of age had a better chance of spontaneous resolution with a larger UDR than children 2 years of age or older. When adjusting for age, grade, laterality and multiple UTIs as covariates, each unit increase of UDR of 0.1 was significantly associated with either persistent VUR (OR = 1.73, 95% CI = 1.02-2.95, P = 0.043) or the need for surgical intervention (OR = 2.40, 95% CI = 1.39-4.17, P = 0.002) compared to spontaneous resolution. When testing the effect of UDR and grade of reflux in the same model, UDR was noted to have a larger effect on predicting failure to spontaneously resolve VUR than grade (Wald Chi-Squared 13.6; P = 0.001 vs 3.62; P = 0.46, respectively). DISCUSSION: The UDR is a readily available objective measurement on the VCUG that has demonstrated ability to enhance the International Reflux Grading System. Limitations of the current review include operative intervention in 12% of the children for failure to improve or resolve VUR. This surgical intervention inhibits determination of spontaneous resolution rates. The findings in this study reflect those in a series of children from a single institution and, therefore, may be impacted by clinical practice bias and geographic variations. Subsequent multi-institutional studies could further define the potential of UDR as either an independent or additive predictive factor for grading VUR that will further permit individualized patient management. CONCLUSION: In this single institution series, UDR was highly correlated with VUR grade; however, UDR proved more predictive of spontaneous resolution, persistence, or operative intervention than grade.

Emotional impact of a video-based suicide prevention program on suicidal viewers and suicide survivors.

In light of continuing concerns about iatrogenic effects associated with suicide prevention efforts utilizing video-based media, the impact of emotionally-charged videos on two vulnerable subgroups--suicidal viewers and suicide survivors--was explored. Following participation in routine suicide education as a part of the U.S. Air Force Suicide Prevention Program's video-based community briefing, a sample of young active duty airmen demonstrated small decreases in positive emotional states and larger decreases in negative emotional states, especially among suicidal females. No evidence of iatrogenic effects were observed among suicidal or survivor subgroups when compared to controls. Results support the use of video-based media as a safe educational strategy that might actually serve to decrease emotional distress among vulnerable subgroups.