Effects of Geopolitical Strain on Global Pharmaceutical Supply Chain Design and Drug Shortages

Pharmaceutical supply chains are global and exhibit geographic and industrial concentration for some drugs. In this context, geopolitical risk and company decisions threaten drug availability, where countries with low manufacturing capacity are most at risk. We present the first supply chain design model that considers geopolitical strain, i.e., export bans and export ban-induced price increases, and the role of alliances in mitigating those risks. Uncertainty is also included in suppliers, production, and demand. The model takes the company's perspective as a decision-maker looking to locate plants and minimize costs by satisfying worldwide demand. The model is solved by integrating the Sample Average Approximation and L-shaped methods. Our case study is based on vincristine, a generic oncology drug. We find that geopolitical strain may reduce shortages in the short term and affect investment decisions and their outcomes. Bilateral alliances between nations result in minor improvements for the company and drug shortages. The results also reveal disparities in drug access. The global expected shortage at the base case is 21%. For high and upper-middle-income countries, expected shortages are 3.1% and 3.7%. However, expected shortages are 98.7% and 95.2% for low and lower-middle-income countries. New pricing policies may improve drug access

The Invisible Slaughter: Local Sea Otter Hunters on the Oregon Coast

Most accounts of the extirpation of sea otters from the Oregon coast focus on the well-documented international maritime fur trade of the late eighteenth and early nineteenth centuries. The historical record shows, however, that sea otters persisted much later. The final extirpation in Oregon occurred as a result of household-scale hunting by Native Americans and Euro-American settlers, from the mid-nineteenth century until around 1910. Especially on the south coast, a cottage industry of sea otter hunting flourished for decades — a pattern similar to the neighboring states of Washington and California. This article summarizes this long-ignored history, drawing from the archival record of local historical societies, late nineteenth century newspapers, reminiscences of settlers, and other contemporary materials

Impact of Active Recovery and Whole-Body Electromyostimulation on Blood-Flow and Blood Lactate Removal in Healthy People

This study aimed to determine whether an active recovery with added whole-body electromyostimulation (WB-EMS) can increase blood flow and lead to blood lactate removal after intense exercise. Thirty-five healthy individuals (23.1 +/- 4.6 years) were randomly assigned to: (a) an experimental group using active recovery together with the WB-EMS (n = 18) or (b) a control group using the same active recovery protocol with the suit with no-stimulation (CON, n = 17). Participants performed a maximal graded exercise test followed by an active recovery protocol (walking at 40% of their maximum aerobic velocity). During the recovery, participants in WB-EMS and CON received continuous stimulation at 7 Hz or no stimulation, respectively. Heart rate, blood lactate concentrations, pain/discomfort, and hemodynamic measurements were recorded before and after the test, and repeated immediately after and at min 30 and 60. The between-group analysis showed a substantially greater Peak blood velocity (-0.27 [-0.68; 0.14]) in WB-EMS compared to CON. The pain/discomfort levels were also lower in WB-EMS compared with CON (0.66 [-0.12; 1.45]). Non-significant differences in participants' blood lactate were observed in WB-EMS compared with CON both immediately; at 30and 60 min. Our findings suggest that increased local blood flow induced by WB-EMS may have contributed to greater lactate removal from active muscles and blood lactate clearance. WB-EMS may be an effective means of increasing muscle blood flow after a maximal graded exercise test and could result in improved recovery

A general dimension of genetic sharing across diverse cognitive traits inferred from molecular data

It has been known since 1904 that, in humans, diverse cognitive traits are positively inter correlated. This forms the basis for the general factor of intelligence (g). Here, we directly test whether there is a partial genetic basis for individual differences in g using data from seven different cognitive tests (N = 11,263 to N = 331,679) and genome-wide autosomal single nucleotide polymorphisms. A genetic g factor accounts for an average of 58.4% (SE = 4.8%) of the genetic variance in the cognitive traits, with the proportion varying widely across traits (range: 9% to 95%). We distill genetic loci that are broadly relevant for many cognitive traits (g) from loci associated specifically with individual cognitive traits. These results contribute to elucidating the etiology of a long-known yet poorly-understood phenomenon, revealing a fundamental dimension of genetic sharing across diverse cognitive traits

Antimicrobial susceptibility patterns of Haemophilus parasuis from pigs in the United Kingdom and Spain

18 p.A total of 30 British and 30 Spanish Haemophilus parasuis isolates were tested for their susceptibility to 19 of the antimicrobials currently used in swine practice with a broth microdilution method in order to know the emergence of resistance against these compounds in this porcine pathogen. All the British isolates were susceptible to penicillin, ceftiofur, erythromycin, tilmicosin, enrofloxacin, and florfenicol, and most of them were susceptible to the remaining antimicrobials (the highest resistance rate found was of 20% to neomycin). In contrast, all the Spanish isolates were susceptible exclusively to florfenicol, and high proportions of resistance were encountered for penicillin, ampicillin, oxytetracycline, erythromycin, tilmicosin, tiamulin and trimethoprim + sulphamethoxazole; in addition, a bimodal or multimodal distribution, or tailing of Spanish isolates over the MIC range was observed for clindamycin, sulphonamides and tylosine tartrate, suggesting the development of acquired resistance. In addition, several multiresistance patterns were found among the Spanish isolates, 23.3% of them being resistant to at least eight antimicrobials, the same rate as that encountered for those being susceptible to all antimicrobials tested. This study showed that in general British H. parasuis isolates are susceptible to antimicrobial agents routinely used for treatment of porcine respiratory diseases; however, the Spanish isolates need a more continuous surveillance of their susceptibility patternsS

Streptococcus suis contains multiple phase-variable methyltransferases that show a discrete lineage distribution

Streptococcus suis is a major pathogen of swine, responsible for a number of chronic and acute infections, and is also emerging as a major zoonotic pathogen, particularly in South-East Asia. Our study of a diverse population of S. suis shows that this organism contains both Type I and Type III phase-variable methyltransferases. In all previous examples, phase-variation of methyltransferases results in genome wide methylation differences, and results in differential regulation of multiple genes, a system known as the phasevarion (phase-variable regulon). We hypothesized that each variant in the Type I and Type III systems encoded a methyltransferase with a unique specificity, and could therefore control a distinct phasevarion, either by recombination-driven shuffling between different specificities (Type I) or by biphasic on-off switching via simple sequence repeats (Type III). Here, we present the identification of the target specificities for each Type III allelic variant from S. suis using single-molecule, real-time methylome analysis. We demonstrate phase-variation is occurring in both Type I and Type III methyltransferases, and show a distinct association between methyltransferase type and presence, and population clades. In addition, we show that the phase-variable Type I methyltransferase was likely acquired at the origin of a highly virulent zoonotic sub-population

Selection and Characterization of a DNA Aptamer Specifically Targeting Human HECT Ubiquitin Ligase WWP1

published_or_final_versio

Prevalence and Determinants of Obesity among Primary School Children in Dar es Salaam, Tanzania.

Childhood obesity has increased dramatically and has become a public health concern worldwide. Childhood obesity is likely to persist through adulthood and may lead to early onset of NCDs. However, there is paucity of data on obesity among primary school children in Tanzania. This study assessed the prevalence and determinants of obesity among primary school children in Dar es Salaam. A cross sectional study was conducted among school age children in randomly selected schools in Dar es Salaam. Anthropometric and blood pressure measurements were taken using standard procedures. Body Mass Index (BMI) was calculated as weight in kilograms divided by the square of height in meters (kg/m2). Child obesity was defined as BMI at or above 95th percentile for age and sex. Socio-demographic characteristics of children were determined using a structured questionnaire. Logistic regression was used to determine association between independent variables with obesity among primary school children in Dar es Salaam. A total of 446 children were included in the analysis. The mean age of the participants was 11.1±2.0 years and 53.1% were girls. The mean BMI, SBP and DBP were 16.6±4.0 kg/m2, 103.9±10.3mmHg and 65.6±8.2mmHg respectively. The overall prevalence of child obesity was 5.2% and was higher among girls (6.3%) compared to boys (3.8%). Obese children had significantly higher mean values for age (p=0.042), systolic and diastolic blood pressures (all p<0.001). Most obese children were from households with fewer children (p=0.019) and residing in urban areas (p=0.002). Controlling for other variables, age above 10 years (AOR=3.3, 95% CI=1.5-7.2), female sex (AOR=2.6, 95% CI=1.4-4.9), urban residence (AOR=2.5, 95% CI=1.2-5.3) and having money to spend at school (AOR=2.6, 95% CI=1.4-4.8) were significantly associated with child obesity. The prevalence of childhood obesity in this population was found to be low. However, children from urban schools and girls were proportionately more obese compared to their counterparts. Primary preventive measures for childhood obesity should start early in childhood and address socioeconomic factors of parents contributing to childhood obesity