Sex and COVID-19 vaccination uptake and intention in the Democratic Republic of Congo, Nigeria, Senegal, and Uganda.

The introduction of vaccines marked a game changer in the fight against COVID-19. In sub-Saharan Africa, studies have documented the intention to vaccinate and the uptake of COVID-19 vaccines. However, little is documented about how sex differences could have impacted COVID-19 vaccination. We conducted a multi-country cross-sectional study to assess the sex differences in COVID-19 vaccine uptake and intention to vaccinate in the Democratic Republic of Congo (DRC), Nigeria, Senegal, and Uganda. This study involved analysis of data from mobile surveys conducted between March and June 2022 among nationally constituted samples of adults in each country. Bivariate and multivariable logistic regression models were run. The self-reported uptake of COVID-19 vaccines was not significantly different between males and females (p = 0.47), while the intention to vaccinate was significantly higher among males (p = 0.008). Among males, obtaining COVID-19 information from health workers, testing for COVID-19, and having high trust in the Ministry of Health were associated with higher vaccination uptake. Among females, having high trust in the government was associated with higher vaccination uptake. For intention to vaccinate, males who resided in semi-urban areas and females who resided in rural areas had significantly higher vaccination intention compared to their counterparts in urban areas. Other factors positively associated with vaccination intention among males were trust in the World Health Organization and perceived truthfulness of institutions, while males from households with a higher socio-economic index and those who had declined a vaccine before had a lower vaccine intention. Overall, the factors differentiating vaccine uptake and intention to vaccinate among males and females were mostly related to trust in government institutions, perceived truthfulness of institutions, and respondent's residence. These factors are key in guiding the tailoring of interventions to increase COVID-19 vaccine uptake in sub-Saharan Africa and similar contexts.

Multifaceted cancer alleviation by cowpea mosaic virus in a bioprinted ovarian cancer peritoneal spheroid model.

Ovarian cancer (OvCa) is a leading cause of mortality among gynecological malignancies and usually manifests as intraperitoneal spheroids that generate metastases, ascites, and an immunosuppressive tumor microenvironment. In this study, we explore the immunomodulatory properties of cowpea mosaic virus (CPMV) as an adjuvant immunotherapeutic agent using an in vitro model of OvCa peritoneal spheroids. Previous findings highlighted the potent efficacy of intratumoral CPMV against OvCa in mouse tumor models. Leveraging the precision control over material deposition and cell patterning afforded by digital-light-processing (DLP) based bioprinting, we constructed OvCa-macrophage spheroids to mimic peritoneal spheroids using gelatin methacrylate (GelMA), a collagen-derived photopolymerizable biomaterial to mimic the extracellular matrix. Following CPMV treatment, bioprinted spheroids exhibited inhibited OvCa progression mediated by macrophage activation. Our analysis indicates that CPMV regulates and activates macrophage to both induce OvCa cell killing and restore normal cell-cell junctions. This study deepened our understanding of the mechanism of CPMV intratumoral immunotherapy in the setting of OvCa. This study also highlights the potential of studying immunotherapies using high throughput tissue models via DLP bioprinting.

Bridging the Clinical-Computational Transparency Gap in Digital Pathology.

CONTEXT.­: Computational pathology combines clinical pathology with computational analysis, aiming to enhance diagnostic capabilities and improve clinical productivity. However, communication barriers between pathologists and developers often hinder the full realization of this potential. OBJECTIVE.­: To propose a standardized framework that improves mutual understanding of clinical objectives and computational methodologies. The goal is to enhance the development and application of computer-aided diagnostic (CAD) tools. DESIGN.­: The article suggests pivotal roles for pathologists and computer scientists in the CAD development process. It calls for increased understanding of computational terminologies, processes, and limitations among pathologists. Similarly, it argues that computer scientists should better comprehend the true use cases of the developed algorithms to avoid clinically meaningless metrics. RESULTS.­: CAD tools improve pathology practice significantly. Some tools have even received US Food and Drug Administration approval. However, improved understanding of machine learning models among pathologists is essential to prevent misuse and misinterpretation. There is also a need for a more accurate representation of the algorithms' performance compared to that of pathologists. CONCLUSIONS.­: A comprehensive understanding of computational and clinical paradigms is crucial for overcoming the translational gap in computational pathology. This mutual comprehension will improve patient care through more accurate and efficient disease diagnosis.

Laser interstitial thermal therapy for first-line treatment of insular glioma.

OBJECTIVE: Insular gliomas pose a significant surgical challenge due to the complex surrounding functional and vascular anatomy. The authors report their experience using a novel framework for the treatment of insular gliomas with laser interstitial thermal therapy (LITT) and provide representative case examples emphasizing indications, rationale, and technical pearls. METHODS: A prospectively gathered institutional database was used to identify patients with newly diagnosed insular gliomas who underwent LITT between 2015 and 2023. The proposed framework of insular glioma management is guided by tumor size and extent of extra-insular tumor involvement. Patients with tumors localized to the insula (insula-only) were treated with single-session or staged LITT. Patients with insular tumors with frontotemporal involvement (insular+) were treated with insular LITT and standard frontotemporal resection of extra-insular tumor. Clinical and volumetric lesional characteristics were analyzed, with particular emphasis on extent of cytoreductive treatment and safety. RESULTS: Of the 261 patients treated at the authors' institution with LITT between 2015 and 2023, 33 LITT procedures were identified involving 22 unique patients with treatment-naive insular gliomas. Of the 22 patients, 12 had insular-only tumors and were treated with LITT alone, while 10 patients had insular+ lesions and were treated with LITT and resection. The median tumor volume for insular-only tumors was 13.4 cm3 (IQR 10.6, 26.3 cm3), with a median extent of treatment of 100% (IQR 92.1%, 100%). Insular+ lesions were significantly larger, with a median volume of 81.2 cm3 (IQR 51.9, 97 cm3) and median extent of treatment of 96.6% (IQR 93.7%, 100%). All patients with insular-only tumors were discharged the day after ablation, while insular+ patients had significantly longer hospital stays, with 50% staying more than 3 days. Overall, 8% of insular-only patients had permanent neurological deficits compared with 33% of insular+ patients. Two patients' tumors progressed during follow-up: one patient with WHO grade 4 astrocytoma and the other with diffuse glioma not otherwise specified. Patients with grade 4 tumors had the highest rate of permanent neurological deficit (43%) and a larger decline in postoperative Karnofsky Performance Status score (p = 0.046). CONCLUSIONS: The authors present their experience using a novel insular glioma treatment paradigm that incorporates LITT into the broader framework of insular glioma surgery. Their findings suggest that insular LITT is feasible and may allow for high rates of cytoreduction while potentially ameliorating the risks of conventional insular glioma surgery.

Revealing the Nature of Binary-Phase on Structural Stability of Sodium Layered Oxide Cathodes.

The emergence of layered sodium transition metal oxides featuring a multiphase structure presents a promising approach for cathode materials in sodium-ion batteries, showcasing notably improved energy storage capacity. However, the advancement of cathodes with multiphase structures faces obstacles due to the limited understanding of the integrated structural effects. Herein, the integrated structural effects by an in-depth structure-chemistry analysis in the developed layered cathode system NaxCu0.1Co0.1Ni0.25Mn0.4Ti0.15O2 with purposely designed P2/O3 phase integration, are comprehended. The results affirm that integrated phase ratio plays a pivotal role in electrochemical/structural stability, particularly at high voltage and with the incorporation of anionic redox. In contrast to previous reports advocating solely for the enhanced electrochemical performance in biphasic structures, it is demonstrated that an inappropriate composite structure is more destructive than a single-phase design. The in situ X-ray diffraction results, coupled with density functional theory computations further confirm that the biphasic structure with P2:O3 = 4:6 shows suppressed irreversible phase transition at high desodiated states and thus exhibits optimized electrochemical performance. These fundamental discoveries provide clues to the design of high-performance layered oxide cathodes for next-generation SIBs.

Unrecoverable lattice rotation governs structural degradation of single-crystalline cathodes.

Transitioning from polycrystalline to single-crystalline nickel-rich cathodes has garnered considerable attention in both academia and industry, driven by advantages of high tap density and enhanced mechanical properties. However, cathodes with high nickel content (>70%) suffer from substantial capacity degradation, which poses a challenge to their commercial viability. Leveraging multiscale spatial resolution diffraction and imaging techniques, we observe that lattice rotations occur universally in single-crystalline cathodes and play a pivotal role in the structure degradation. These lattice rotations prove unrecoverable and govern the accumulation of adverse lattice distortions over repeated cycles, contributing to structural and mechanical degradation and fast capacity fade. These findings bridge the previous knowledge gap that exists in the mechanistic link between fast performance failure and atomic-scale structure degradation.

Contemporary outcomes for resected type 1-3 gastroesophageal junction adenocarcinoma: a single-center experience.

BACKGROUND: Surgical resection remains the mainstay of treatment for tumors of the gastroesophageal junction (GEJ). However, contemporary analyses of the Western experience for GEJ adenocarcinoma are sparsely reported. METHODS: Patients with GEJ adenocarcinoma undergoing resection between 2012 and 2022 at a single institution were grouped based on Siewert subtype and analyzed. Pathologic and treatment related variables were assessed with relation to outcomes. RESULTS: A total of 302 patients underwent resection: 161 (53.3%) with type I, 116 (38.4%) with type II, and 25 (8.3%) with type III tumors. Most patients received neoadjuvant therapy (86.4%); 86% of cases were performed in a minimally invasive fashion. Anastomotic leak occurred in 6.0% and 30-day mortality in only 0.7%. The rate of grade 3+ morbidity was lower for the last 5 years of the study than for the first 5 years (27.5% vs 49.3%, P < .001), as was median length of stay (7 vs 8 days, P < .001). There was a significantly greater number of signet ring type tumors among type III tumors (44.0%) than type I/II tumors (11.2/12.9%, P < .001). Otherwise, there was no difference in the distribution of pathologic features among Siewert subtypes. Notably, there was a significant difference in 3-year overall survival based on Siewert classification: type I 60.0%, type II 77.2%, and type III 86.3% (P = .011). Siewert type I remained independently associated with worse survival on multivariable analysis (hazard ratio, 4.5; P = .023). CONCLUSIONS: In this large, single-institutional series, operative outcomes for patients with resected GEJ adenocarcinoma improved over time. On multivariable analysis, type I tumors were an independent predictor of poor survival.

Democratizing Artificial Intelligence in Anatomic Pathology.

CONTEXT.­: Artificial intelligence is a transforming technology for anatomic pathology. Involvement within the workforce will foster support for algorithm development and implementation. OBJECTIVE.­: To develop a supportive ecosystem that enables pathologists with variable expertise in artificial intelligence to create algorithms in a development environment with seamless transition to a production environment. RESULTS.­: The development team considered internal development and vended solutions. Because of the extended timeline and resource requirements for internal development, a decision was made to use a vended solution. Vendor proposals were solicited and reviewed by pathologists, IT, and security groups. A vendor was selected and pipelines for development and production were established. Proposals for development were solicited from the pathology department. Eighty-four investigators were selected for the initial cohort, receiving training and access to dedicated subject matter experts. A total of 30 of 31 projects progressed through the model development process of annotating, training, and validation. Based on these projects, 15 abstracts were submitted to national meetings. CONCLUSIONS.­: Democratizing artificial intelligence by creating an ecosystem to support pathologists with varying levels of expertise can break down entry barriers, reduce overall cost of algorithm development, improve algorithm quality, and enhance the speed of adoption.

Health workforce incentives and dis-incentives during the COVID-19 pandemic: experiences from Democratic Republic of Congo, Nigeria, Senegal, and Uganda.

BACKGROUND: The COVID-19 pandemic presented a myriad of challenges for the health workforce around the world due to its escalating demand on service delivery. A motivated health workforce is critical to effectual emergency response and in some settings, incentivizing health workers motivates them and ensures continuity in the provision of health services. We describe health workforce experiences with incentives and dis-incentives during the COVID-19 response in the Democratic Republic of Congo (DRC), Senegal, Nigeria, and Uganda. METHODS: This is a multi-country qualitative research study involving four African countries namely: DRC, Nigeria, Senegal, and Uganda which assessed the workplace incentives instituted in response to the COVID-19 pandemic. Key informant interviews (n = 60) were conducted with staff at ministries of health, policy makers and health workers. Interviews were virtual using the telephone or Zoom. They were audio recorded, transcribed verbatim, and analyzed thematically. Themes were identified and quotes were used to support findings. RESULTS: Health worker incentives included (i) financial rewards in the form of allowances and salary increments. These motivated health workers, sustaining the health system and the health workers' efforts during the COVID-19 response across the four countries. (ii) Non-financial incentives related to COVID-19 management such as provision of medicines/supplies, on the job trainings, medical care for health workers, social welfare including meals, transportation and housing, recognition, health insurance, psychosocial support, and supervision. Improvised determination and distribution of both financial and non-financial incentives were common across the countries. Dis-incentives included the lack of personal protective equipment, lack of transportation to health facilities during lockdown, long working hours, harassment by security forces and perceived unfairness in access to and inadequacy of financial incentives. CONCLUSION: Although important for worker motivation, financial and non-financial incentives generated some dis-incentives because of the perceived unfairness in their provision. Financial and non-financial incentives deployed during health emergencies should preferably be pre-determined, equitably and transparently provided because when arbitrarily applied, these same financial and non-financial incentives can potentially become dis-incentives. Moreover, financial incentives are useful only as far as they are administered together with non-financial incentives such as supportive and well-resourced work environments. The potential negative impacts of interventions such as service delivery re-organization and lockdown within already weakened systems need to be anticipated and due precautions exercised to reduce dis-incentives during emergencies.

Control of DNA replication in vitro using a reversible replication barrier.

A major obstacle to studying DNA replication is that it involves asynchronous and highly delocalized events. A reversible replication barrier overcomes this limitation and allows replication fork movement to be synchronized and localized, facilitating the study of replication fork function and replication coupled repair. Here we provide details on establishing a reversible replication barrier in vitro and using it to monitor different aspects of DNA replication. DNA template containing an array of lac operator (lacO) sequences is first bound to purified lac repressor (LacR). This substrate is then replicated in vitro using a biochemical replication system, which results in replication forks stalled on either side of the LacR array regardless of when or where they arise. Once replication forks are synchronized at the barrier, isopropyl-ß-D-thiogalactopyranoside can be added to disrupt LacR binding so that replication forks synchronously resume synthesis. We describe how this approach can be employed to control replication fork elongation, termination, stalling and uncoupling, as well as assays that can be used to monitor these processes. We also explain how this approach can be adapted to control whether replication forks encounter a DNA lesion on the leading or lagging strand template and whether a converging fork is present. The required reagents can be prepared in 1-2 weeks and experiments using this approach are typically performed over 1-3 d. The main requirements for utilizing the LacR replication barrier are basic biochemical expertise and access to an in vitro system to study DNA replication. Investigators should also be trained in working with radioactive materials.

Use of tobacco and other illicit drugs among adolescent boys and young men in Kampala, Uganda: A result of low parental attention?

INTRODUCTION: Although the use of illicit drugs is common among young people, limited data exists on the use of illicit drugs among adolescent boys and young men (ABYM). We assessed the use of tobacco, marijuana and khat among ABYM to inform the design of harm-reduction interventions. METHODS: This secondary analysis uses data from a formative study conducted among 2,500 ABYM across the five divisions of Kampala between July and August 2020. Survey questions were adopted from the Global Youth Tobacco Survey and Global School-based Student Health Survey. We computed proportions of ABYM that had ever used any form of tobacco or marijuana or khat in the past year and the proportion that had used any of these products in the past 30 days (i.e. 'current users'). In a sub-group analysis, we assessed if any patterns existed between ABYM's use of illicit drugs and selected parental attention attributes. RESULTS: Of 2,500 ABYM, 47.3% (n = 1,182) were aged 15-19 years. Overall, 16.4% (n = 410) reported past-year use of tobacco products while 11.6% (n = 289) and 10.5% (n = 263) reported past-year use of marijuana and khat, respectively. Current use of any illicit drugs was higher among past-year khat (46%, n = 133) and marijuana users (36.9%, n = 97) than past-year tobacco users (4%, n = 17). Current use of any illicit drugs was higher among out-of-school than in-school ABYM and increased with increasing age and education levels. However, parental attention was lower among out-of-school than in-school ABYM and decreased with increasing age and education levels. CONCLUSION: Use of illicit drugs is common among ABYM and increased with age and education levels but parental attention among current illicit drug users decreased with increasing age and education levels. These findings suggest that interventions intended to improve parental attention among illicit drug users may help to reduce the prevalence of illicit drug use among ABYM.

Prenatal Household Air Pollution Exposure and Childhood Blood Pressure in Rural Ghana.

BACKGROUND: The association between prenatal household air pollution (HAP) exposure and childhood blood pressure (BP) is unknown. OBJECTIVE: Within the Ghana Randomized Air Pollution and Health Study (GRAPHS) we examined time-varying associations between a) maternal prenatal and b) first-year-of-life HAP exposure with BP at 4 years of age and, separately, whether a stove intervention delivered prenatally and continued through the first year of life could improve BP at 4 years of age. METHODS: GRAPHS was a cluster-randomized cookstove intervention trial wherein n=1,414 pregnant women were randomized to one of two stove interventions: a) a liquefied petroleum gas (LPG) stove or improved biomass stove, or b) control (open fire cooking). Maternal HAP exposure over pregnancy and child HAP exposure over the first year of life was quantified by repeated carbon monoxide (CO) measurements; a subset of women (n=368) also performed one prenatal and one postnatal personal fine particulate matter (PM2.5) measurement. Systolic and diastolic BP (SBP and DBP) were measured in n=667 4-y-old children along with their PM2.5 exposure (n=692). We examined the effect of the intervention on resting BP z-scores. We also employed reverse distributed lag models to examine time-varying associations between a) maternal prenatal and b) first-year-of-life HAP exposure and resting BP z-scores. Among those with PM2.5 measures, we examined associations between PM2.5 and resting BP z-scores. Sex-specific effects were considered. RESULTS: Intention-to-treat analyses identified that DBP z-score at 4 years of age was lower among children born in the LPG arm (LPG ß=-0.20; 95% CI: -0.36, -0.03) as compared with those in the control arm, and females were most susceptible to the intervention. Higher CO exposure in late gestation was associated with higher SBP and DBP z-score at 4 years of age, whereas higher late-first-year-of-life CO exposure was associated with higher DBP z-score. In the subset with PM2.5 measurements, higher maternal postnatal PM2.5 exposure was associated with higher SBP z-scores. DISCUSSION: These findings suggest that prenatal and first-year-of-life HAP exposure are associated with child BP and support the need for reductions in exposure to HAP, with interventions such as cleaner cooking beginning in pregnancy. https://doi.org/10.1289/EHP13225.

Elucidating Local Structure and Positional Effect of Dopants in Colloidal Transition Metal Dichalcogenide Nanosheets for Catalytic Hydrogenolysis.

Tailoring nanoscale catalysts to targeted applications is a vital component in reducing the carbon footprint of industrial processes; however, understanding and controlling the nanostructure influence on catalysts is challenging. Molybdenum disulfide (MoS2), a transition metal dichalcogenide (TMD) material, is a popular example of a nonplatinum-group-metal catalyst with tunable nanoscale properties. Doping with transition metal atoms, such as cobalt, is one method of enhancing its catalytic properties. However, the location and influence of dopant atoms on catalyst behavior are poorly understood. To investigate this knowledge gap, we studied the influence of Co dopants in MoS2 nanosheets on catalytic hydrodesulfurization (HDS) through a well-controlled, ligand-directed, tunable colloidal doping approach. X-ray absorption spectroscopy and density functional theory calculations revealed the nonmonotonous relationship between dopant concentration, location, and activity in HDS. Catalyst activity peaked at 21% Co:Mo as Co saturates the edge sites and begins basal plane doping. While Co prefers to dope the edges over basal sites, basal Co atoms are demonstrably more catalytically active than edge Co. These findings provide insight into the hydrogenolysis behavior of doped TMDs and can be extended to other TMD materials.

Research rigor and reproducibility in research education: A CTSA institutional survey.

We assessed the rigor and reproducibility (R&R) activities of institutions funded by the National Center for Advancing Translational Sciences (NCTSA) through a survey and website search (N = 61). Of 50 institutional responses, 84% reported incorporating some form of R&R training, 68% reported devoted R&R training, 30% monitored R&R practices, and 10% incentivized them. Website searches revealed 9 (15%) freely available training curricula, and 7 (11%) institutional programs specifically created to enhance R&R. NCATS should formally integrate R&R principles into its translational science models and institutional requirements.

Pd-CeO2 catalyst facilely derived from one-pot generated Pd@Ce-BTC for low temperature CO oxidation.

Due to the capacity to offer abundant catalytic sites within porous solids featuring high surface areas, metal-organic frameworks (MOFs) and their derivatives have garnered considerable attention as prospective catalysts in environmental catalysis. To promote the industrial application of MOFs, there is an urgent need for an effective and environmental-friendly preparation approach. Breaking through the limitation of the traditional two-step preparation method that Pd was introduced to the already prepared Ce-BTC (Pd/Ce-BTC, BTC = 1, 3, 5 benzenetricarboxylate), in this work, we present a novel one-pot solvothermal method for synthesizing the Pd material supported by Ce-BTC (Pd@Ce-BTC). After pyrolysis in N2 flow or air flow, Pd-CeO2 catalysts derived from Pd@Ce-BTC exhibited much higher CO oxidation activity than those from Pd/Ce-BTC. Moreover, Pd/Ce-BTC and Pd@Ce-BTC pyrolyzed in N2 flow (Pd/Ce-BTC-N and Pd@Ce-BTC-N) could better catalyze the oxidation of CO than Pd/Ce-BTC and Pd@Ce-BTC pyrolyzed in air flow (Pd/Ce-BTC-A and Pd@Ce-BTC-A). Further characterizations revealed that the abundant surface Ce3+ species, rich surface adsorbed oxygen species and superior redox properties were the main reasons for the superior CO oxidation activity of Pd@Ce-BTC-N.

Improving maternal and neonatal outcomes among pregnant women who are HIV-positive or HIV-negative through the Saving Mothers Giving Life initiative in Uganda: An analysis of population-based mortality surveillance data.

HIV infection is associated with poor maternal health outcomes. In 2016, the maternal mortality ratio (MMR) in Uganda was 336/100,000, and the neonatal mortality rate (NMR) was 19/1,000. Saving Mothers, Giving Life (SMGL) was a five-year maternal and neonatal health strengthening initiative launched in 2012 in Uganda. We extracted maternal and neonatal data for 2015-2016 from the initiative's population-based mortality surveillance system in 123 health facilities in Western Uganda. We collected data on the facilities, HIV status, antiretroviral drug (ARV) use, death, birth weight, delivery type, parity, Apgar scores, and complications. We compared mother and baby outcomes between HIV-positive or HIV-negative, computed risk ratios (RR) for adverse outcomes, and used the chi-square to test for significance in differences observed. Among 116,066 pregnant women who attended and gave birth at SMGL-implementing facilities during 2015-2016, 8,307 (7.7%) were HIV-positive, of whom 7,809 (94%) used antiretroviral drugs (ARVs) at the time of delivery. During birth, 23,993 (21%) women experienced ≥1 complications. Neonate Apgar scores <7 (8.8%) and maternal haemorrhage during birth (1.6%) were the most common outcomes. Overall facility MMR was 258/100,000 and NMR was 7.6/1,000. HIV infection increased risk of maternal death (RR = 3.6, 95% Confidence Interval (CI) = 2.4-5.5), maternal sepsis (RR = 2.1, 95% CI = 1.3-3.3), and infant birth weight <2,500g (RR = 1.2, 95% CI = 1.1-1.3), but was protective against maternal complications (RR = 0.92, 95% CI = 0.87-0.97) and perinatal death (RR = 0.78, 95% CI = 0.68-0.89). Among the HIV-positive, ARV non-use increased risk of maternal death (RR = 15, 95% CI = 7.1-31) and perinatal death (RR = 2.3, 95% CI = 1.6-3.4). SMGL reduced facility MMR and NMR below national rates. HIV-infection was associated with maternal sepsis and death. Failure to use ARVs among women living with HIV increased the risk of maternal and perinatal death. Use of the SMGL approach and complementary interventions that further strengthen HIV care, may continue to reduce MMR and NMR.

A New Look at P Values for Randomized Clinical Trials.

BACKGROUND: We have examined the primary efficacy results of 23,551 randomized clinical trials from the Cochrane Database of Systematic Reviews. METHODS: We estimate that the great majority of trials have much lower statistical power for actual effects than the 80 or 90% for the stated effect sizes. Consequently, "statistically significant" estimates tend to seriously overestimate actual treatment effects, "nonsignificant" results often correspond to important effects, and efforts to replicate often fail to achieve "significance" and may even appear to contradict initial results. To address these issues, we reinterpret the P value in terms of a reference population of studies that are, or could have been, in the Cochrane Database. RESULTS: This leads to an empirical guide for the interpretation of an observed P value from a "typical" clinical trial in terms of the degree of overestimation of the reported effect, the probability of the effect's sign being wrong, and the predictive power of the trial. CONCLUSIONS: Such an interpretation provides additional insight about the effect under study and can guard medical researchers against naive interpretations of the P value and overoptimistic effect sizes. Because many research fields suffer from low power, our results are also relevant outside the medical domain. (Funded by the U.S. Office of Naval Research.)

Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts.

A role for substance P has been proposed in musculoskeletal fibrosis, with effects mediated through transforming growth factor beta (TGFß). We examined the in vitro effects of substance P on proliferation, collagen secretion, and collagen deposition in rat primary dermal fibroblasts cultured in medium containing 10% fetal bovine serum, with or without TGFß. In six-day cultures, substance P increased cell proliferation at concentrations from 0.0002 to 100 nM. TGFß increased proliferation at concentrations from 0.0002 to 2 pg/mL, although higher concentrations inhibited proliferation. Substance P treatment alone at concentrations of 100, 0.2, and 0.00002 nM did not increase collagen deposition per cell, yet when combined with TGFß (5 ng/mL), increased collagen deposition compared to TGFß treatment alone. Substance P treatment (100 nM) also increased smooth muscle actin (SMA) expression at 72 h of culture at a level similar to 5 ng/mL of TGFß; only TGFß increased SMA at 48 h of culture. Thus, substance P may play a role in potentiating matrix deposition in vivo when combined with TGFß, although this potentiation may be dependent on the concentration of each factor. Treatments targeting substance P may be a viable strategy for treating fibrosis where both substance P and TGFß play roles.