Palm Beach Research Center

Cerebrospinal fluid (CSF) is a clear, transparent fluid derived from blood plasma that protects the brain and spinal cord against mechanical shock, provides buoyancy, clears metabolic waste and transports extracellular components to remote sites in the brain. Given its contact with the brain and the spinal cord, CSF is the most informative biofluid for studies of the central nervous system (CNS). In addition to other components, CSF contains extracellular vesicles (EVs) that carry bioactive cargoes (e.g., lipids, nucleic acids, proteins), and that can have biological functions within and beyond the CNS. Thus, CSF EVs likely serve as both mediators of and contributors to communication in the CNS. Accordingly, their potential as biomarkers for CNS diseases has stimulated much excitement for and attention to CSF EV research. However, studies on CSF EVs present unique challenges relative to EV studies in other biofluids, including the invasive nature of CSF collection, limited CSF volumes and the low numbers of EVs in CSF as compared to plasma. Here, the objectives of the International Society for Extracellular Vesicles CSF Task Force are to promote the reproducibility of CSF EV studies by providing current reporting and best practices, and recommendations and reporting guidelines, for CSF EV studies. To accomplish this, we created and distributed a world‐wide survey to ISEV members to assess methods considered ‘best practices’ for CSF EVs, then performed a detailed literature review for CSF EV publications that was used to curate methods and resources. Based on responses to the survey and curated information from publications, the CSF Task Force herein provides recommendations and reporting guidelines to promote the reproducibility of CSF EV studies in seven domains: (i) CSF Collection, Processing, and Storage; (ii) CSF EV Separation/Concentration; (iii) CSF EV Size and Number Measurements; (iv) CSF EV Protein Studies; (v) CSF EV RNA Studies; (vi) CSF EV Omics Studies and (vii) CSF EV Functional Studies.

ObjectivesTo assess the effects of BWCs on prosecutorial and court-related charge outcomes across multiple crime types, including domestic violence charges, crimes committed against police officers, and drug/alcohol charges.MethodsA cluster-randomized controlled trial with 22 spatiotemporal police units assigned to BWCs and 17 assigned to control conditions. Data from the State Attorney’s Office were used to track convictions, adjudication withheld dispositions, and declined prosecutions for both experimental and control charges. A series of multilevel logistic and negative binomial regression models were used to estimate the effect of BWC footage on charge outcomes.OutcomesBWCs led to a significantly higher proportion of crimes against police officers resulting in convictions or adjudication withheld outcomes, and a significantly higher proportion of domestic violence charges resulting in convictions alone, compared to control charges. However, after the clustering effect was taken into account, only the effect of BWCs on crimes against police officers remained statistically significant.ConclusionThese early results suggest that BWCs have significant evidentiary value that varies by crime type. BWCs may be best suited to capture evidence of crimes committed against police officers and potentially in domestic violence offenses as well.

Background:In the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection.Methods:Through case-cohort sampling, participants were selected for measurement of four serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57: IgG binding antibodies (bAbs) to Spike, bAbs to Spike receptor-binding domain (RBD), and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers calibrated to the WHO International Standard (cID50 and cID80). Participants with no evidence of previous SARS-CoV-2 infection were included. Cox regression assessed in vaccine recipients the association of each Day 29 or 57 serologic marker with COVID-19 through 126 or 100 days of follow-up, respectively, adjusting for risk factors.Results:Day 57 Spike IgG, RBD IgG, cID50, and cID80 neutralization levels were each inversely correlated with risk of COVID-19: hazard ratios 0.66 (95% CI 0.50, 0.88; p=0.005); 0.57 (0.40, 0.82; p=0.002); 0.42 (0.27, 0.65; p<0.001); 0.35 (0.20, 0.61; p<0.001) per 10-fold increase in marker level, respectively, multiplicity adjusted P-values 0.003–0.010. Results were similar for Day 29 markers (multiplicity adjusted P-values <0.001–0.003). For vaccine recipients with Day 57 reciprocal cID50 neutralization titers that were undetectable (<2.42), 100, or 1000, respectively, cumulative incidence of COVID-19 through 100 days post Day 57 was 0.030 (0.010, 0.093), 0.0056 (0.0039, 0.0080), and 0.0023 (0.0013, 0.0036). For vaccine recipients at these titer levels, respectively, vaccine efficacy was 50.8% (−51.2, 83.0%), 90.7% (86.7, 93.6%), and 96.1% (94.0, 97.8%). Causal mediation analysis estimated that the proportion of vaccine efficacy mediated through Day 29 cID50 titer was 68.5% (58.5, 78.4%).Conclusions:Binding and neutralizing antibodies correlated with COVID-19 risk and vaccine efficacy and likely have utility in predicting mRNA-1273 vaccine efficacy against COVID-19.Trial registration number:COVE ClinicalTrials.gov number, NCT04470427

Introduction Home hemodialysis has not been widely adopted despite superior outcomes relative to conventional in-center hemodialysis. Patients receiving home hemodialysis experience high rates of technique failure owing to machine complexity, training burden, and the inability to master treatments independently. Methods We conducted human factors testing on 15 health care professionals (HCPs) and 15 patients upon release of the defined training program on the Tablo™ Hemodialysis System. Each participant completed one training and one testing session conducted in a simulated clinical environment. Training sessions lasted <3 hours for HCPs and <4 hours for patients, with an hour break between sessions for knowledge decay. During the testing session, we recorded participant behavior and data according to standard performance and safety-based criteria. Findings Of 15 HCPs, 10 were registered nurses and five patient care technicians, with a broad range of dialysis work experience and no limitations other than visual correction. Of 15 patients (average age 48 years), 13 reported no limitations and two reported modest limitations-partial deafness and blindness in one eye, respectively. The average error rate was 4.4 per session for HCPs and 2.9 per session for patients out of a total possible 1,710 opportunities for errors. Despite having received minimal training, neither HCPs nor patients committed safety-related errors that required mitigation; rather, we noted only minor errors and operational difficulties. Discussion The Tablo™ Hemodialysis System is easy to use, and may help to enable self-care and home hemodialysis in settings heretofore associated with high rates of technique failure.

This study examined the effects of the Boys Town In-Home Family Program (BT-IHFP) on parenting skills, family functioning, and child behavior for at-risk families involved with child protective services. The BT-IHFP is designed as a home-based, family-centered alternative to out-of-home placement with the goal of improving family functioning, keeping families together, and preventing further involvement with child protective services. The model uses a hands-on cognitive-behavioral approach, promotes family engagement, provides 24/7 services to families, and links families to community resources. While it is essential to examine ultimate, long-term outcomes such as family preservation, it is also important to investigate the proximal and intermediate outcomes that address the key changes in behavior that support successful long-term outcomes. The goals of this study were to (1) examine the pre-post change of proximal and intermediate outcomes and (2) examine if improvements in parenting skills, parental roles, and parental stress (proximal outcomes) will be related to improvements in child behavior at home, child behavior at school, and family functioning (intermediate outcomes). Inspecting intake and discharge data for 44 families, 94% were intact at discharge and significant pre-post improvements were found in proximal and intermediate outcomes. These findings suggest that this six-week intensive BT-IHFP holds promise for teaching at-risk families skills to promote positive family functioning.

This debate has been around for decades and will be around for decades more yet. I write in support of the sound contribution from Ross Cutler and Greg Cronin.1 I was one of those who 40 years ago was encouraging farmers to house their pigs and that included the use of dry sow stalls. For those who want the pigs back outside, I list a few of the problems with pigs outdoors in Australia. Social stress and bullying, sunburn, lack of individual attention from the stockman, worrying by dogs, interactions with feral pigs and escaping. Diseases such as mange, worms, swine dysentery, thin sow syndrome and bowel impaction with sand and gravel. Biosecurity risks from exotic and endemic diseases, some of which are zoonoses such as salmonellosis leptospirosis and erysipelas. Pigs root in the soil and do lots of damage, destroying plants and disturbing the soil and contributing to soil erosion. Free range pigs need a lot of space, which escalates costs. Housing pigs does not prevent all the problems listed above, but it does make it possible for the stockman to see health problems and treat them in a timely and effective manner. Pigs that are mostly outside are difficult to handle and distressed by handling unless the group size is small. Housed pigs are usually much more easily handled and this difference is substantial and much of the reason for housing pigs. Pig production is very competitive and those still in production are only there because their skills and commitment allow them to continue. About 25 years ago I was the first speaker at a seminar for pig farmers. My topic was Management of the Sow and Litter. There were about 90 people present and I needed to check on who I was talking to, so I asked for a show of hands of those who had that morning worked in their piggery. Most of those present put their hands up. Then I asked how many had talked to their pigs? Two hands went up, then some more and I waited and gradually all the same hands went up. I, a veterinarian, had their attention. Livestock management comes from being receptive to the needs of the stock. Calling that factory farming is derogatory and misleading. The next issue to address is the background of the people voicing concerns about factory farming and sow stalls. Do they enjoy eating pork? Have they discussed their concerns with a pig farmer or at least someone who is properly abreast of all the issues that concerned people raise? Welfare Codes have been worked on at length. Situations change, so changes may be needed, but I think it legitimate to pause while consideration is given for the reasons to change and who is calling for the changes.