Search

Abstract X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.

Summary: The 20 short tandem repeat (STR) loci of the combined DNA index system (CODIS) are the basis of the vast majority of forensic genetics in the United States. One argument for permissive rules about the collection of CODIS genotypes is that the CODIS loci are thought to contain little information about ancestry or traits. However, in the past 20 years, a growing field has identified hundreds of thousands of genotype-trait associations. Here, we conduct a survey of the landscape of such associations surrounding the CODIS loci as compared with non-CODIS STRs. Although this study cannot establish or quantify associations between CODIS genotypes and phenotypes, we find that the regions around the CODIS loci are enriched for both known pathogenic variants (> 90th percentile) and for trait-associated SNPs identified in genome-wide association studies (GWAS) (≥ 95th percentile in 10kb and 100kb flanking regions), compared with other random sets of autosomal tetranucleotide-repeat STRs.

Median arcuate ligament syndrome is a rare and poorly understood condition that can have a significant impact on the quality of life of patients. Diagnosis is often difficult and delayed because of the need to exclude other pathologic processes. Treatment strategies traditionally involve open or laparoscopic division of the median arcuate ligament, with or without vascular reconstruction. This report portrays a case of median arcuate ligament syndrome with compression of two visceral arteries and distal embolic complications. A novel hybrid technique is described using intravascular ultrasound technology to aid in laparoscopic median arcuate ligament division. This allowed real-time intravascular visualization of the compressive segment, guided release of the ligament fibers, and demonstrated confirmation of decompression. Keywords: Vascular surgery, Intravascular ultrasound, Median arcuate ligament syndrome

Abstract To examine whether single-nucleotide polymorphism (SNP) by methylation interactions can be detected, we analyzed GAW20 simulated triglycerides at visits 3 and 4 against baseline (visits 1 and 2) under 4 general linear models and 2 tree-based models in 200 replications of a sample of 680 individuals. Effects for SNPs, methylation cytosine-phosphate-guanine (CpG) effects, and interactions for SNP/CpG pairs were included. Causative SNPs/CpG pairs distributed on autosomal chromosomes 1 to 20 were tested to examine sensitivity. We also tested noncausative SNP/CpG pairs on chromosomes 21 and 22 to estimate the empirical null. We found reasonable power to detect the main causative loci, with the exact power depending on sample size and strength of effects at the SNP and CpG sites.

Objectives: High-quality research is fundamental to the advancement of surgical practice. Currently, there is no quantitative assessment of the research output of vascular surgeons in Australia and New Zealand. By conducting this bibliometric analysis, we aim to provide an objective representation of the trends in vascular surgery and guide future research. Methods: A list of all current vascular surgeons in Australia and New Zealand was compiled from the Royal Australasian College of Surgeons ‘Find a Surgeon’ website tool and correlated with the Australia and New Zealand Society for Vascular Surgery database. A Scopus search of each surgeon’s author profile over the last 20 years was conducted. Results: In total, 2120 articles were published by 208 Australasian vascular surgeons between 1998 and July 2018, with an overall increase in publications over time. Audits or case series were the most published type of study and only 8% of the publications were of high-level evidence. The most popular topics were thoracoabdominal aortic pathologies (24%), followed by peripheral arterial disease (15%). Chronological analysis illustrates an increasing volume of peripheral arterial disease research over time and there is a clear trend towards more endovascular and hybrid surgery publications. The top 10 (5%) highest publishing authors by h-index account for 41% of all publications and 49% of all citations and are also responsible for producing significantly more high-level evidence research. Conclusion: Australasian vascular surgeons have made a significant contribution to medical research. However, the majority of these articles are of low-level evidence. In this time, there has been an increasing number of publications on endovascular and hybrid surgery in keeping with the trend in clinical practice. These areas, as well as research regarding peripheral arterial disease, show potential for high-evidence research in the future.

The mammalian transient receptor potential melastatin channel 8 (TRPM8) is highly expressed in trigeminal and dorsal root ganglia. TRPM8 is activated by cold temperature or compounds that cause a cooling sensation, such as menthol or icilin. TRPM8 may play a role in cold hypersensitivity and hyperalgesia in various pain syndromes. Therefore, TRPM8 antagonists are pursued as therapeutics. In this study we explored the feasibility of blocking TRPM8 activation with antibodies. We report the functional characterization of a rabbit polyclonal antibody, ACC-049, directed against the third extracellular loop near the pore region of the human TRPM8 channel. ACC-049 acted as a full antagonist at recombinantly expressed human and rodent TRPM8 channels in cell based agonist-induced 45Ca2+ uptake assays. Further, several poly-and monoclonal antibodies that recognize the same region also blocked icilin activation of not only recombinantly expressed TRPM8, but also endogenous TRPM8 expressed in rat dorsal root ganglion neurons revealing the feasibility of generating monoclonal antibody antagonists. We conclude that antagonist antibodies are valuable tools to investigate TRPM8 function and may ultimately pave the way for development of therapeutic antibodies.

Quantiles and expected shortfalls are commonly used risk measures in financial risk management. The two measurements are correlated while having distinguished features. In this project, our primary goal is to develop a stable and practical inference method for the conditional expected shortfall. We consider the joint modelling of conditional quantile and expected shortfall to facilitate the statistical inference procedure. While the regression coefficients can be estimated jointly by minimizing a class of strictly consistent joint loss functions, the computation is challenging, especially when the dimension of parameters is large since the loss functions are neither differentiable nor convex. We propose a two‐step estimation procedure to reduce the computational effort by first estimating the quantile regression parameters with standard quantile regression. We show that the two‐step estimator has the same asymptotic properties as the joint estimator, but the former is numerically more efficient. We develop a score‐type inference method for hypothesis testing and confidence interval construction. Compared to the Wald‐type method, the score method is robust against heterogeneity and is superior in finite samples, especially for cases with many confounding factors. The advantages of our proposed method over existing approaches are demonstrated by simulations and empirical studies based on income and college education data. [ABSTRACT FROM AUTHOR]

Background Ischemia/reperfusion injury (IRI) is one of the most predominant complications of ischemic heart disease. Gastrin has emerged as a regulator of cardiovascular function, playing a key protective role in hypoxia. Serum gastrin levels are increased in patients with myocardial infarction, but the pathophysiogical significance of this finding is unknown. The purpose of this study was to determine whether and how gastrin protects cardiac myocytes from IRI. Methods and Results Adult male Sprague‐Dawley rats were used in the experiments. The hearts in living rats or isolated Langendorff‐perfused rat hearts were subjected to ischemia followed by reperfusion to induce myocardial IRI. Gastrin, alone or with an antagonist, was administered before the induction of myocardial IRI. We found that gastrin improved myocardial function and reduced the expression of myocardial injury markers, infarct size, and cardiomyocyte apoptosis induced by IRI. Gastrin increased the phosphorylation levels of ERK1/2 (extracellular signal‐regulated kinase 1/2), AKT (protein kinase B), and STAT3 (signal transducer and activator of transcription 3), indicating its ability to activate the RISK (reperfusion injury salvage kinase) and SAFE (survivor activating factor enhancement) pathways. The presence of inhibitors of ERK1/2, AKT, or STAT3 abrogated the gastrin‐mediated protection. The protective effect of gastrin was via CCK2R (cholecystokinin 2 receptor) because the CCK2R blocker CI988 prevented the gastrin‐mediated protection of the heart with IRI. Moreover, we found a negative correlation between serum levels of cardiac troponin I and gastrin in patients with unstable angina pectoris undergoing percutaneous coronary intervention, suggesting a protective effect of gastrin in human cardiomyocytes. Conclusions These results indicate that gastrin can reduce myocardial IRI by activation of the RISK and SAFE pathways.

Analyzing the tail quantiles of a response distribution is sometimes more important than analyzing the mean in biomarker studies. Inferences in a quantile regression are complicated when there exist a large number of candidate markers, together with some prespecified controlled covariates. In this study, we develop a new and simple testing procedure to detect the effects of biomarkers in a high-dimensional quantile regression in the presence of protected covariates. The test is based on the maximum-score-type statistic obtained from a conditional marginal regression. We establish the asymptotic properties of the proposed test statistic under both null and alternative hypotheses and propose an alternative multiplier bootstrap method, with theoretical justifications. We use numerical studies to show that the proposed method provides adequate controls of the family-wise error rate with competitive power, and that it can also be used as a stopping rule in a forward regression. The proposed method is applied to a motivating genome-wide association study to detect single nucleotide polymorphisms associated with low glomerular filtration rates in type 1 diabetes patients. [ABSTRACT FROM AUTHOR]

Spatial cluster detection, which is the identification of spatial units adjacent in space associated with distinctive patterns of data of interest relative to background variation, is useful for discerning spatial heterogeneity in regression coefficients. Some real studies with regression‐based models on air quality data show that there exists not only spatial heterogeneity but also heteroscedasticity between air pollution and its predictors. Since the low air quality is a well‐known risk factor for mortality, various cardiopulmonary diseases, and preterm birth, the analysis at the tail would be of more interest than the center of air pollution distribution. In this article, we develop a spatial cluster detection approach using a threshold quantile regression model to capture the spatial heterogeneity and heteroscedasticity. We introduce two threshold variables in the quantile regression model to define a spatial cluster. The proposed test statistic for identifying the spatial cluster is the supremum of the Wald process over the space of threshold parameters. We establish the limiting distribution of the test statistic under the null hypothesis that the quantile regression coefficient is the same over the entire spatial domain at the given quantile level. The performance of our proposed method is assessed by simulation studies. The proposed method is also applied to analyze the particulate matter (PM2.5) concentration and aerosol optical depth (AOD) data in the Northeastern United States in order to study geographical heterogeneity in the association between AOD and PM2.5 at different quantile levels. [ABSTRACT FROM AUTHOR]

This study examines the estimation of extreme conditional quantiles for distributions with Weibull-type tails. We propose two families of estimators for the Weibull tail-coefficient, and construct an extrapolation estimator for the extreme conditional quantiles based on a quantile regression and extreme value theory. The asymptotic results of the proposed estimators are established. This work fills a gap in the literature on extreme quantile regressions, where many important Weibull-type distributions are excluded by the assumed strong conditions. A simulation study shows that the proposed extrapolation method provides estimations of the conditional quantiles of extreme orders that are more efficient and stable than those of the conventional method. The practical value of the proposed method is demonstrated through an analysis of extremely high birth weights. [ABSTRACT FROM AUTHOR]

In many applications, subgroups with different parameters may exist even after accounting for the covariate effects, and it is important to identify the meaningful subgroups for better medical treatment or market segmentation. We propose a robust subgroup identification method based on median regression with concave fusion penalizations. The proposed method can simultaneously determine the number of subgroups, identify the group membership for each subject, and estimate the regression coefficients. Without requiring any parametric distributional assumptions, the proposed method is robust against outliers in the response and heteroscedasticity in the regression error. We develop a convenient algorithm based on local linear approximation, and establish the oracle property of the proposed penalized estimator and the model selection consistency for the modified Bayesian information criteria. The numerical performance of the proposed method is assessed through simulation and the analysis of a heart disease data. [ABSTRACT FROM AUTHOR]

Inference and prediction in quantile regression for longitudinal data are challenging without parametric distributional assumptions. We propose a new semi- parametric approach that uses copula to account for intra-subject dependence and approximates the marginal distributions of longitudinal measurements, given covariates, through regression of quantiles. The proposed method is exible, and it can provide not only efficient estimation of quantile regression coefficients but also prediction intervals for a new subject given the prior measurements and covariates. The properties of the proposed estimator and prediction are established theoretically, and assessed numerically through a simulation study and the analysis of a nursing home data. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal neurons lacking CDKL5 show decreased dendritic complexity but a trend toward increased spine density. This morphological change is accompanied by an increase in the frequency of spontaneous miniature EPSCs and interestingly, miniature IPSCs. Using voltage-sensitive dye imaging to interrogate the evoked response of the CA1 microcircuit, we find that CA1 pyramidal neurons lacking CDKL5 show hyperexcitability in their dendritic domain that is constrained by elevated inhibition in a spatially and temporally distinct manner. These results suggest a novel role for CDKL5 in the regulation of synaptic function and uncover an intriguing microcircuit mechanism underlying impaired learning and memory. [ABSTRACT FROM AUTHOR]

Background: Medicines use related challenges such as inadequate adherence, high levels of antimicrobial resistance and preventable adverse drug reactions have underscored the need to incorporate pharmaceutical services to help achieve desired treatment outcomes, and protect patients from inappropriate use of medicines. This situation is further constrained by insufficient numbers of pharmaceutical personnel and inappropriate skill mix. Studies have addressed individual capacity building approaches of logistics, supply chain or disease specific interventions but few have documented those involving such pharmacy assistants/professionals, or health workers/professionals charged with improving access and provision of pharmaceutical services. We examined how different training modalities have been employed and adapted to meet country-specific context and needs by a global pharmaceutical systems strengthening program in collaboration with a country's Ministry of Health and local stakeholders. Methods: Structured, content analysis of training approaches from twelve selected countries and a survey among conveniently selected trainees in Bangladesh and Ethiopia. Results: Case-based learning, practice and feedback, and repetitive interventions such as post-training action plan, supportive supervision and mentoring approaches are effective, evidence-based training techniques. In Ethiopia and Bangladesh, over 94% of respondents indicated that they have improved or developed skills or competencies as a result of the program's training activities. Supportive supervision structures and mentorship have been institutionalized with appropriate management structures. National authorities have been sensitized to secure funding from domestic resources or from the global fund grants for post-training follow-up initiatives. The Pharmaceutical Leadership Development Program is an effective, case-based training modality that motivates staff to develop quality-improvement interventions and solve specific challenges. Peer-to-peer learning mechanisms than traditional didactic methods was a preferred intervention among high level government officials both within country and between countries. Conclusion: Interventions must involve local institutions in the design and delivery of content for both pre-service and in-service training as well as web-based methods where feasible. Such efforts would meet the changing demand in the pharmaceutical system, and promote the ownership of the human capacity development interventions. The cost-effective partnership with universities demonstrate that competency based pre-service training will prepare the future pharmaceutical workforce with a critical foundation of knowledge and skills required to meet the growing demand for patient-centered pharmaceutical services in resource-constrained countries. [ABSTRACT FROM AUTHOR]

Ralls v. CFIUS is the first and only CFIUS challenge that has been heard by United States federal courts. In granting standing to the foreign investor, the DC Circuit determined that the purchaser had gained protectable property interests and was therefore guaranteed due process rights. However, this privilege is circumscribed insofar as factual considerations cannot touch on issues of national security and classified sources. These limitations render the "justiciability" of CFIUS decisions toothless, much in the same way that Article XXI issues are effectively non-justiciable before the GATT Panel. [ABSTRACT FROM AUTHOR]

We provide a general method to calculate and maximize the purity of a qubit interacting with an anisotropic non-Markovian environment. Counter to intuition, we find that the purity is often maximized by preparing and storing the qubit in a superposition of noninteracting eigenstates. For a model relevant to decoherence of a heavy-hole spin qubit in a quantum dot or for a singlet-triplet qubit for two electrons in a double quantum dot, we show that preparation of the qubit in its noninteracting ground state can actually be the worst choice to maximize purity. We further give analytical results for spin-echo envelope modulations of arbitrary spin components of a hole spin in a quantum dot, going beyond a standard secular approximation. We account for general dynamics in the presence of a pure-dephasing process and identify a crossover time scale at which it is again advantageous to initialize the qubit in the noninteracting ground state. Finally, we consider a general two-axis dynamical decoupling sequence and determine initial conditions that maximize purity, minimizing leakage to the environment. [ABSTRACT FROM AUTHOR]

We develop a theory for the spin-echo dynamics of a heavy hole in a quantum dot, accounting for both hyperfine- and electric-field-induced fluctuations. We show that a moderate applied magnetic field can drive this system to a motional-averaging regime, making the hyperfine interaction ineffective as a decoherence source. Furthermore, we show that decay of the spin-echo envelope is highly sensitive to the geometry. In particular, we find a specific choice of initialization and π-pulse axes which can be used to study intrinsic hyperfine-induced hole-spin dynamics, even in systems with substantial electric-field-induced dephasing. These results point the way to designed hole-spin qubits as a robust and long-lived alternative to electron spins. [ABSTRACT FROM AUTHOR]

We studied N-(2-aminoethyl)-N-(4-(benzyloxy)-3-methoxybenzyl)thiophene-2-carboxamide hydrochloride (M8-B), a selective and potent antagonist of the transient receptor potential melastatin-8 (TRPM8) channel. In vitro, M8-B blocked cold-induced and TRPM8- agonist-induced activation of rat, human, and murine TRPM8 channels, including those on primary sensory neurons. In vivo, M8-B decreased deep body temperature (Tb) in Trpm8&plus;/&plus; mice and rats, but not in Trpm8-/- mice, thus suggesting an on-target action. Intravenous administration of M8-B was more effective in decreasing Tb in rats than intrathecal or intracerebroventricular administration, indicating a peripheral action. M8-B attenuated cold-induced c-Fos expression in the lateral parabrachial nucleus, thus indicating a site of action within the cutaneous cooling neural pathway to thermoeffectors, presumably on sensory neurons. A low intravenous dose of M8-B did not affect Tb at either a constantly high or a constantly low ambient temperature (Ta), but the same dose readily decreased Tb if rats were kept at a high Ta during the M8-B infusion and transferred to a low Ta immediately thereafter. These data suggest that both a successful delivery of M8-B to the skin (high cutaneous perfusion) and the activation of cutaneousTRPM8channels (by cold) are required for the hypothermic action of M8-B. At tail-skin temperatures<23°C, the magnitude of the M8-B-induced decrease in Tb was inversely related to skin temperature, thus suggesting that M8-B blocks thermal (cold) activation of TRPM8. M8-B affected all thermoeffectors studied (thermopreferendum, tail-skin vasoconstriction, and brown fat thermogenesis), thus suggesting that TRPM8 is a universal cold receptor in the thermoregulation system. [ABSTRACT FROM AUTHOR]

We propose a new approach for analyzing skewed and heteroscedastic health care cost data through regression of the conditional quantiles of the transformed cost. Using the appealing equivariance property of quantiles to monotone transformations, we propose a distribution-free estimator of the conditional mean cost on the original scale. The proposed method is extended to a two-part heteroscedastic model to account for zero costs commonly seen in health care cost studies. Simulation studies indicate that the proposed estimator has competitive and more robust performance than existing estimators in various heteroscedastic models. [ABSTRACT FROM PUBLISHER]

Mammography screening rates among Chinese American women have been reported to be low. This study examines whether and how culture views and language ability influence mammography adherence in this mostly immigrant population. Asymptomatic Chinese American women (n = 466) aged 50 and older, recruited from the Washington, D.C. area, completed a telephone interview. Regular mammography was defined as having two mammograms at age-appropriate recommended intervals. Cultural views were assessed by 30 items, and language ability measured women's ability in reading, writing, speaking, and listening to English. After controlling for risk perception, worry, physician recommendation, family encouragement, and access barriers, women holding a more Chinese/Eastern cultural view were significantly less likely to have had regular mammograms than those having a Western cultural view. English ability was positively associated with mammography adherence. The authors' results imply that culturally sensitive and language-appropriate educational interventions are likely to improve mammography adherence in this population. [ABSTRACT FROM AUTHOR]

While the advent of ICT has produced mixed results for the travel agency businesses, one of the differentiating factors has been how different businesses have strategically responded to the new business environment. In view of the threats and opportunities presented by ICTs to the travel sector, this study sought to examine the different strategies adopted by the travel agents in Kenya in an effort to strategically reposition themselves. The survey was conducted among 55 travel agency operators in Nairobi, Kenya using a semi-structured questionnaire. The study found out that travel agents in Kenya have adopted a number of ICT innovations to stay afloat. Among the most significant strategic innovations has been the travel agent’s increased client focus as opposed to focus on service providers. This has seen the travel agents forge close relationships with their clients through both online and offline approaches. It is imperative to note that investing in customers and developing a strong relationship marketing strategy to attract and retain them is the new area of competitiveness today. This study thus provides a new perspective to the strategic response of travel agencies to macro-environmental threats and opportunities presented by current developments in ICTs.

The relativistic binary-encounter-dipole (RBED) model for electron-impact ionization of atoms combines classical binary-encounter theory and the asymptotic dipole interaction, which is based on the plane-wave Born approximation, with the only non-trivial ingredient being the optical oscillator strength (OOS). Due to the difficulty of obtaining accurate OOSs, the performance of the RBED model has so far not been fully assessed. In the present work we compare RBED inner-shell ionization cross sections (total and differential) of neutral atoms evaluated using three types of OOSs, namely an empirical power-law OOS, analytical hydrogenic OOSs and ab initio OOSs calculated numerically from self-consistent atomic potentials. We find that, compared to the distorted-wave Born approximation (DWBA), the RBED with either hydrogenic or numerical OOSs generally yields more accurate total cross sections (TCSs) than the RBED with the power-law OOS, especially for the most tightly bound shells. In the highly relativistic limit the RBED model does not recover the Bethe asymptotic behavior because of its different energy-dependent prefactor, hence we investigate an alternative prefactor which restores the correct Bethe asymptote. Finally, we suggest multiplying the RBED differential cross sections (DCSs) by the ratio of DWBA to RBED TCSs and verify that this renormalization improves the agreement with the DWBA DCSs. [ABSTRACT FROM AUTHOR]

Mouse models of CDKL5 deficiency disorder (CDD) recapitulate multiple clinical symptoms of CDD, such as intellectual disability and autism. Here, the authors show that selective loss of CDKL5 from GABAergic neurons leads to social deficits and stereotypic behaviors, which can be ameliorated through inhibition of NMDAR signaling.

The overall aim of the current paper is to establish best practices for developing, engaging and working critically in virtual intercultural communication. The need to build practical language communication skills is not a new idea or a new part of methodology. With the development of technology, the range of communicative opportunities has grown and allowed virtual intercultural dialogues to take place. The focus of these situations is not only language development and practice, but also critical cultural awareness and intercultural skill development. The paper presents contrasting approaches in the methodological construction of one such programme between young students in Entel Foreign Language School, China, and Krosno State College, Poland. Over the course of the link from Spring to Summer 2017, different approaches were taken by the instructors and students in both countries resulting in varying levels of engagement and critical understanding. The Chinese approach stresses communication as an outcome and delivers more time to oral activities in the classroom, which contrasts with the Polish approach of a stricter language-based teaching strategy. As a result, the paper will discuss the relative merits of the two methodological frameworks in the communication project. This will be achieved by evaluating the overall success of the communication based on interviews with the student participants and observations of interaction during the link meetings. Finally, the paper will illustrate a methodology for working with such links and developing intercultural communication.

Background Medicines use related challenges such as inadequate adherence, high levels of antimicrobial resistance and preventable adverse drug reactions have underscored the need to incorporate pharmaceutical services to help achieve desired treatment outcomes, and protect patients from inappropriate use of medicines. This situation is further constrained by insufficient numbers of pharmaceutical personnel and inappropriate skill mix. Studies have addressed individual capacity building approaches of logistics, supply chain or disease specific interventions but few have documented those involving such pharmacy assistants/professionals, or health workers/professionals charged with improving access and provision of pharmaceutical services. We examined how different training modalities have been employed and adapted to meet country-specific context and needs by a global pharmaceutical systems strengthening program in collaboration with a country’s Ministry of Health and local stakeholders. Methods Structured, content analysis of training approaches from twelve selected countries and a survey among conveniently selected trainees in Bangladesh and Ethiopia. Results Case-based learning, practice and feedback, and repetitive interventions such as post-training action plan, supportive supervision and mentoring approaches are effective, evidence-based training techniques. In Ethiopia and Bangladesh, over 94% of respondents indicated that they have improved or developed skills or competencies as a result of the program’s training activities. Supportive supervision structures and mentorship have been institutionalized with appropriate management structures. National authorities have been sensitized to secure funding from domestic resources or from the global fund grants for post-training follow-up initiatives. The Pharmaceutical Leadership Development Program is an effective, case-based training modality that motivates staff to develop quality-improvement interventions and solve specific challenges. Peer-to-peer learning mechanisms than traditional didactic methods was a preferred intervention among high level government officials both within country and between countries. Conclusion Interventions must involve local institutions in the design and delivery of content for both pre-service and in-service training as well as web-based methods where feasible. Such efforts would meet the changing demand in the pharmaceutical system, and promote the ownership of the human capacity development interventions. The cost-effective partnership with universities demonstrate that competency based pre-service training will prepare the future pharmaceutical workforce with a critical foundation of knowledge and skills required to meet the growing demand for patient-centered pharmaceutical services in resource-constrained countries.