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In 2022, San Joaquin County had approximately 2,319 unhoused/unsheltered individuals, with 66% residing in Stockton. Studies have found that approximately 75% of unhoused individuals reported drug use of any kind and 12% reported opioid use. Additionally, drug overdosedeaths increased in the United States by more than 30% from 2019 to 2020. Transmission rates of infections associated with injection drug use have also been increasing. Harm reduction services, including syringe exchange and naloxone distribution, have been shown toreduce the rates of disease transmission and drug overdose death within communities.In 2016, the rate of drug-induced deaths was 56% higher in San Joaquin County than the California state average. Developed in July 2020, The Stockton Harm ReductionProgram (SHRP) provides sterile syringes and injection equipment, condoms, naloxone, hygiene products, and referrals for health and housing services to people in San Joaquin County. The purpose of this study is to determine the impact of a mobile harm reduction program on usage of sterilesyringes and naloxone by program participants.

Antibodies are used in many areas of biomedical and clinical research, but many of these antibodies have not been adequately characterized, which casts doubt on the results reported in many scientific papers. This problem is compounded by a lack of suitable control experiments in many studies. In this article we review the history of the antibody characterization crisis, and we document efforts and initiatives to address the problem, notably for antibodies that target human proteins. We also present recommendations for a range of stakeholders - researchers, universities, journals, antibody vendors and repositories, scientific societies and funders - to increase the reproducibility of studies that rely on antibodies.

Antibodies are critical reagents to detect and characterize proteins. It is commonly understood that many commercial antibodies do not recognize their intended targets, but information on the scope of the problem remains largely anecdotal, and as such, feasibility of the goal of at least one potent and specific antibody targeting each protein in a proteome cannot be assessed. Focusing on antibodies for human proteins, we have scaled a standardized characterization approach using parental and knockout cell lines (Laflamme et al., 2019) to assess the performance of 614 commercial antibodies for 65 neuroscience-related proteins. Side-by-side comparisons of all antibodies against each target, obtained from multiple commercial partners, have demonstrated that: (i) more than 50% of all antibodies failed in one or more applications, (ii) yet, ~50-75% of the protein set was covered by at least one high-performing antibody, depending on application, suggesting that coverage of human proteins by commercial antibodies is significant; and (iii) recombinant antibodies performed better than monoclonal or polyclonal antibodies. The hundreds of underperforming antibodies identified in this study were found to have been used in a large number of published articles, which should raise alarm. Encouragingly, more than half of the underperforming commercial antibodies were reassessed by the manufacturers, and many had alterations to their recommended usage or were removed from the market. This first study helps demonstrate the scale of the antibody specificity problem but also suggests an efficient strategy toward achieving coverage of the human proteome; mine the existing commercial antibody repertoire, and use the data to focus new renewable antibody generation efforts.

Background: Lumbar microdiscectomy is a surgical procedure that is frequently used in the treatment of symptomatic lumbar herniation. Differences in outcomes following primary and revision lumbar microdiscectomy have been previously studied, with reports of comparably satisfactory results from the Spine Patient Outcomes Research Trial. In this study, we further investigate these outcomes, including length of stay, bleeding events, and durotomy. We hypothesized that length of stay, incidence of bleeding events, and dural tear would be greater in the revision cohort. Methods: The ACS-National Surgical Quality Improvement Program database was queried for patients undergoing single-level primary and revision lumbar microdiscectomy between 2019 and 2022. Eligibility for inclusion was determined by age >18 years and current procedural terminology codes 63030 and 63042. Patients with preoperative sepsis or cancer were excluded. Length of stay, wound infection, bleeding events requiring transfusion, cerebrospinal fluid leak, dural tear, and neurological injury were compared between the cohorts. Multivariable Poisson regression adjusted for demographics and comorbidities, including age, sex, race, body mass index, diabetes, smoking, and hypertension, was used to determine if revision was predictive of complications. Results: A total of 37,669 patients were included, of whom 3,635 (9.6%) required revision surgery. Patients in the revision cohort were older (54.25 ± 15.7 vs. 50.85 ± 16.0 years, P < 0.001) and had higher proportions of male (59.0% vs. 55.7%, P < 0.001) and non-Hispanic White patients (82.0% vs. 77.4%, P < 0.001). Length of stay (1.11 ± 2.5 vs. 1.58 ± 2.7, P < 0.001) and rates of wound infection (2.1% vs. 1.4%, P = 0.002) and bleeding events requiring transfusion (1.3% vs. 0.7%, P < 0.001) were greater in the revision cohort compared to primary patients. Differences in cerebrospinal fluid leak (0.2% vs. 0.1%, P = 0.116), dural tear complication (0.01% vs. 0.01%, P = 0.092), and neurological injury (0.008% vs. 0.006%, P = 0.691) between the revision and primary cohorts were nonsignificant. Poisson log-linear regression adjusted for demographics and comorbidities demonstrated revision as a significant predictor for length of stay (χ2 = 462.95, P < 0.001), wound infection (χ2 = 9.22, P = 0.002), and bleeding events (χ2 = 9.74, P = 0.002), while it was a nonsignificant predictor of cerebrospinal fluid leak (χ2 = 2.61, P = 0.106), dural tear (χ2 = 2.37, P = 0.123), and neurological injury (χ2 = 0.229, P = 0.632). Conclusion: Revision surgery was a significant predictor of increased length of stay, wound infection, and bleeding events requiring transfusion. Surgeons and patients alike should be aware of increased risk for complications following revision lumbar microdiscectomy compared to primary discectomy.

Introduction: Mastectomy skin necrosis (MSN) is a common complication occurring in up to 50% of patients. In patients with risk factors for poor wound healing such as immunosuppression, prior radiotherapy (XRT), and high body mass index (BMI > 30.0), this number is even higher. MSN can lead to infection, loss of reconstruction, poorer aesthetics, and most ominously, delay in adjuvant cancer therapy. Instead of forgoing reconstruction in these patients, adjunctive therapies to optimize wound healing are necessary. The purpose of this study is to introduce the use of cryopreserved umbilical tissue (vCUT) as an adjunct therapy for high-risk-wound-healing immediate breast reconstruction (IBR) patients. Methods: All patients who underwent breast reconstruction with vCUT as an adjunctive therapy were identified and retrospectively analyzed. Results: Seven patients who underwent breast reconstruction with vCUT placement were identified. These patients had risk factors for delayed healing, such as obesity, immunosuppression, and/or prior XRT. The mean post-operative follow-up was 252 days (range 183–287). Four out of seven patients demonstrated post-operative complications: two out of seven developed seromas, two out of seven developed wound dehiscence, two out of seven developed infection, two out of seven developed MSN, and two out of seven lost their reconstruction. Conclusion: As undergoing IBR leads to improved mental health and superior aesthetic outcomes, efforts to expand current indications for safe IBR to traditionally poorer reconstructive candidates are imperative. The results of this case series demonstrate vCUT as a promising novel adjunctive tool in the reconstructive surgeons’ armamentarium in managing the less ideal reconstructive breast candidate.

With recent advances in spray technology and rising interest in site-specific applications, it is imperative to assess the performance of the latest application technologies to ensure effective pesticide applications. Thus, a study was conducted to compare and evaluate the performance of two different flow control systems [rate controller (RC) and pulse width modulation (PWM)] on an agricultural sprayer while simulating different site-specific application scenarios. A custom data acquisition and logging system was developed to record the real-time nozzle flow and pressure across the sprayer boom. The first experiment measured the response time to achieve different target application rates in single-rate site-specific (On/Off) states at varying simulated ground speeds. The second experiment examined the response time for rate transitions in variable-rate application scenarios among different selected target rates at varying simulated ground speeds. Across all the application scenarios, the PWM system consistently outperformed the RC system in terms of response time and rate stabilization. Specifically, the PWM system exhibited significantly lower mean rate stabilization times compared to the RC system during single-rate application states. Similarly, in the variable-rate application states—where the rate transitions were evaluated—the PWM system consistently displayed shorter mean rate transition and stabilization times compared to the RC system. Overall, the findings from this study suggest PWM systems tend to be more responsive and effective, making them the preferred choice for efficient precision site-specific pesticide applications. Future research should evaluate the influence of other operational parameters such as look-ahead time and ground speed variations on the performance of both systems in actual field applications.

Background and Aims: Postoperative pain can impede functional recovery and delay hospital discharge after functional endoscopic sinus surgery (FESS). The study aimed to assess the efficacy of ultrasound (USG)-guided suprazygomatic maxillary nerve block (SZMNB) for postoperative pain in FESS. Methods: Forty-eight adult patients between 18 and 65 years of age with American Society of Anesthesiologists physical status I and II and scheduled to undergo FESS were enroled in this randomised controlled study. Patients were randomly allocated to either receive USG-guided SZMNB with general anaesthesia (n = 24) or general anaesthesia alone (n = 24). The numerical rating scale (NRS) pain score in the immediate postoperative period was recorded as the primary outcome. A total of 24 h postoperative rescue analgesic consumption, surgeon satisfaction score, postoperative haemodynamics, and postoperative complications were noted as secondary outcomes. Results: The median (interquartile range) of the NRS pain score in the immediate postoperative period was 0 (0-0.25)[95% confidence interval (CI): 0, 0.08] in the block group compared to 2 (1.75-3) [95% CI: 1.60, 2.40] in the control group, P < 0.001]. Pain scores were significantly reduced at all time intervals till 24 h after surgery (P < 0.001). None of the patients required rescue analgesia in the block group. In contrast, eight patients required diclofenac 75 mg intravenous as rescue analgesia within 1 h of surgery and ten patients within 1–6 h of surgery in the control group. Other secondary outcomes were comparable between groups (P > 0.05). Conclusion: The USG-guided SZMNB provides excellent postoperative analgesia for patients undergoing FESS without significant side effects.

Abstract Background Spontaneous pneumothorax (PTX) is more prevalent among COVID-19 patients than other critically ill patients, but studies on this are limited. This study compared clinical characteristics and in-hospital outcomes among COVID-19 patients with concomitant PTX to provide insight into how PTX affects health care utilization and complications, which informs clinical decisions and healthcare resource allocation. Methods The 2020 Nationwide Inpatient Sample was used analyze patient demographics and outcomes, including age, race, sex, insurance status, median income, length of hospital stay, mortality rate, hospitalization costs, comorbidities, mechanical ventilation, and vasopressor support. Propensity score matching was employed for additional analysis. Results Among 1,572,815 COVID-19 patients, 1.41% had PTX. These patients incurred significantly higher hospitalization costs ($435,508 vs. $96,668, p

Abstract Background The National Comprehensive Cancer Network (NCCN) guideline recommends consideration of weekly cisplatin as an alternative option for patients with head and neck cancer undergoing definitive chemoradiation. However, in a recent phase III trial (ConCERT), 20% of patients treated with weekly cisplatin could not receive a total of 200 mg/m2, and the association of low adherence to weekly cisplatin and cancer control outcomes remains unclear. To fill this knowledge gap, we performed an observational cohort study of patients with head and neck cancer undergoing definitive chemoradiation with weekly cisplatin. Methods Our institutional database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation with weekly cisplatin (40 mg/m2) between November 2007 and April 2023. Adherence to weekly cisplatin was defined as receiving at least 5 cycles with a total cumulative dose of 200 mg/m2. Survival outcomes were evaluated using Kaplan–Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Logistic MVA was performed to identify variables associated with low adherence to weekly cisplatin. Fine-Gray MVA was performed to analyze failure outcomes with death as a competing event. Results Among 119 patients who met our criteria, 51 patients (42.9%) had low adherence to weekly cisplatin. Median follow up was 19.8 months (interquartile range 8.8–65.6). Low adherence to weekly cisplatin was associated with worse overall survival (adjusted hazards ratio [aHR] 2.94, 95% confidence interval [CI] 1.58–5.47, p

ABSTRACT: Background: Prior studies have linked sarcopenia and fat infiltration in paraspinal muscles with lumbar pain, spinal pathology, and adverse postoperative outcomes in lumbar spine surgery. A recent magnetic resonance imaging (MRI)-based method for assessing muscle health, incorporating parameters such as Goutallier Classification (GC) and the Paralumbar Muscle Cross-Sectional Area to Body Mass Index ratio (PL-CSA/BMI), has shown that higher muscle grades correlate with significant improvements in patient-reported outcomes. Despite these advancements, there is limited research on the associations between paralumbar muscle health and factors such as age, BMI, walking tolerability, and spondylolisthesis. Our study aimed to evaluate such associations. Methods: This Institutional Review Board-approved retrospective cohort study included patients aged 18 or older presenting with back pain symptoms who underwent lumbar spine MRI within 12 months of presentation to a single orthopedic surgeon. Patients with incomplete imaging, cancer pathology, or trauma-induced injuries were excluded. MRI-based measurements of Lumbar Indentation Value (LIV), Goutallier Classification (GC), and PL-CSA/BMI were used as outcome measures. Paralumbar muscles on axial T2-weighted lumbar MRIs were outlined using ImageJ to determine the PL-CS and LIV through the L1–L5 disc spaces, with GC classified by the primary author. Quantile regression analysis was used for continuous variables, and negative binomial regression with an estimated ancillary parameter was applied for ordinal variables, with statistical significance set at p 1 block predicted LIV and GC at L2/L3 while predicting CSA/BMI at L4/L5. Increasing age was associated with decreased CSA at L1/L2, L2/L3 and L4/L5 while it was associated with decreased CSA/BMI and increased GC at all lumbar levels. Age was only associated with decreased LIV at L1/L2, L2/L3. Lastly, increasing BMI was associated with increased CSA, LIV, and decreased CSA/BMI at all lumbar levels and associated with increased GC at all lumbar levels except L4/L5. All statistically significant associations had p-values

ABSTRACTSince the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710–1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group – Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.

ABSTRACTAntibodies are one of the most important reagents used in biomedical and fundamental research, used to identify, and quantify proteins, contribute to knowledge of disease mechanisms, and validate drug targets. Yet many antibodies used in research do not recognize their intended target, or recognize additional molecules, compromising the integrity of research findings and leading to waste of resources, lack of reproducibility, failure of research projects, and delays in drug development. Researchers frequently use antibodies without confirming that they perform as intended in their application of interest. Here we argue that the determinants of end-user antibody choice and use are critical, and under-addressed, behavioral drivers of this problem. This interacts with the batch-to-batch variability of these biological reagents, and the paucity of available characterization data for most antibodies, making it more difficult for researchers to choose high quality reagents and perform necessary validation experiments. The open-science company YCharOS works with major antibody manufacturers and knockout cell line producers to characterize antibodies, identifying high-performing renewable antibodies for many targets in neuroscience. This shows the progress that can be made by stakeholders working together. However, their work so far applies to only a tiny fraction of available antibodies. Where characterization data exists, end-users need help to find and use it appropriately. While progress has been made in the context of technical solutions and antibody characterization, we argue that initiatives to make best practice behaviors by researchers more feasible, easy, and rewarding are needed. Global cooperation and coordination between multiple partners and stakeholders will be crucial to address the technical, policy, behavioral, and open data sharing challenges. We offer potential solutions by describing our Only Good Antibodies initiative, a community of researchers and partner organizations working toward the necessary change. We conclude with an open invitation for stakeholders, including researchers, to join our cause.

OBJECTIVES:. To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400. DESIGN:. Prospective population pharmacokinetic study of vancomycin. SETTING:. Critically ill patients in quaternary care PICUs. PATIENTS:. Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the ICUs at the University of Maryland Children’s Hospital and Texas Children’s Hospital were enrolled. INTERVENTIONS:. Vancomycin was prescribed at doses and intervals chosen by the treating clinicians. MEASUREMENTS AND MAIN RESULTS:. A median of four serum levels of vancomycin per patient were collected along with other variables for up to 7 days following the first administration. These data were used to characterize vancomycin pharmacokinetics and evaluate the factors affecting the variability in achieving AUC24/MIC ratio greater than or equal to 400 in PICU patients who are not on extracorporeal therapy. A total of 302 children with a median age of 6.0 years were enrolled. A two-compartment model described the pharmacokinetics of vancomycin with the clearance of 2.76 L/hr for a typical patient weighing 20 kg. The glomerular filtration rate estimated using either the bedside Schwartz equation or the chronic kidney disease in children equation was the only statistically significant predictor of clearance among the variables evaluated, exhibiting equal predictive performance. The trough levels achieving AUC24/MIC = 400 were 5.6–10.0 μg/mL when MIC = 1 μg/mL. The target of AUC24/MIC greater than or equal to 400 was achieved in 60.4% and 36.5% with the typical dosing regimens of 15 mg/kg every 6 and 8 hours (q6h and q8h), respectively. CONCLUSIONS:. The pharmacokinetics of vancomycin in critically ill children were dependent on the estimated glomerular filtration rate only. Trough concentrations accurately predict AUC24. Typical pediatric vancomycin dosing regimens of 15 mg/kg q6h and q8h will often lead to AUC24/MIC under 400.

Introduction Blood transfusion is crucial, but low-income and middle-income countries like India face a severe shortage of banked blood. This study focuses on the Empowered Action Group (EAG) states in India, where healthcare is limited, and health outcomes are poor. Our objective was to assess the blood banking infrastructure and access to blood products in these states.Methods We used e-Rakht Khosh, an online platform for blood availability data. We collected data on blood bank locations and stocks from 18 January to 9 February 2022 and used ArcGIS to determine the population residing within 30–60–90 min of a blood bank. Availability ratios were calculated by dividing available blood products by population in these catchment areas. Descriptive analysis characterised availability, and statistical tests evaluated differences across states and over the 4-week period.Results 806 of 824 blood banks reported data on blood stocks. Our analysis showed that 25.72% of the EAG states’ population live within 30 min of a blood bank, while 61.45% and 92.46% live within 60 and 90 min, respectively.Conclusion Blood availability rates were low in the EAG states, with only 0.6 units per 1000 people. Additionally, only 61% of the population had access to blood-equipped facilities within an hour. These rates fell below the standards of the Lancet Commission on Global Surgery (15 units per 1000 population) and the WHO (10 donations per 1000 population). The study highlights the challenges in meeting demand for blood in emergencies due to inadequate blood banking infrastructure.