Dynamic inventory pooling policies to deliver differentiated service

Resource pooling strategies have been widely used in industry to match supply with demand. However, effective implementation of these strategies can be challenging. Firms need to integrate the heterogeneous service level requirements of different customers into the pooling model and allocate the resources (inventory or capacity) appropriately in the most effective manner. The traditional analysis of inventory pooling, for instance, considers the performance metric in a centralized system and does not address the associated issue of inventory allocation. Using Blackwell’s Approachability Theorem, we derive a set of necessary and sufficient conditions to relate the fill rate requirement of each customer to the resources needed in the system. This provides a new approach to studying the value of resource pooling in a system with differentiated service requirements. Furthermore, we show that with “allocation flexibility,” the amount of safety stock needed in a system with independent and identically distributed demands does not grow with the number of customers but instead diminishes to zero and eventually becomes negative as the number of customers grows sufficiently large. This surprising result holds for all demand distributions with bounded first and second moments. This paper was accepted by Martin Lariviere, operations management. </jats:p

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

Purification and functional characterization of brain and recombinant chimaerin, a p21rac GTPase activating protein

n-chimaerin is a GAP for the ras-related p21rac. A 45 kDa brain protein (p45) immune reactive to anti-n-chimaerin polyclonal antibodies had selective p21 rac GAP activity, using an overlay assay. p45-chimaerin was purified 400- fold from rat brain by column chromatography. Tryptic peptides contained sequences identical to that predicted from α2-chimaerin cDNA, a splice variant encoding a divergent N-terminal with a SH2 domain. Thus, p45-chimaerin probably corresponds to SH2-containing (α2) chimaerin. A 35 kDa p21rac GAP (p35) detected in detergent soluble membrane fractions, immunoreactive to chimaerin antiserum was likely to represent n-chimaerin (α1-chimaerin). Diverse GAPs for the rho/rac family were present in the brain; p45-chimaerin was widely distributed in brain regions except cerebellum, and was present in both membrane and cytosolic fractions. Both native and recombinant a2-chimaerin exhibited p21rac GAP activity in solution, which was stimulated by phosphatidylserine with a synergistic effect by phorbol esters. GAP activity of α2-chimaerin was unaffected by its SH2 domain. In contrast to α1-chimaerin, α2-chimaerin bound more phorbol ester in the presence of phosphatidylinositol than of phosphatidylserine. α2-Chimaerin was phosphorylated by PKC and PKA in vitro. Brain proteins interacting with α2-chimaerin were detected using 32P-labelled PKC phosphorylated chimaerin. A 60 kDa protein interacting with the SH2 domain of α2-chimaerin was purified; peptide sequences showed it to be novel. Two peptides had similarity to the consensus sequences of a MAP kinase substrate and a SH2 binding domain. These data suggest that α2-chimaerin plays a physiological role in neuronal signal transduction involving SH2-linked receptor/tyrosine kinase and p21rac signalling pathways

Bike-Repositioning Using Volunteers: Crowd Sourcing with Choice Restriction

Motivated by the Bike Angels Program in New York's Citi Bike and Boston's Blue Bikes, we study the use of (registered) volunteers to re-position empty bikes for riders in a bike sharing system. We propose a method that can be used to deploy the volunteers in the system, based on the real time distribution of the bikes in different stations. To account for (random) route demand in the network, we solve a related transshipment network design model and construct a sparse structure to restrict the re-balancing activities of the volunteers (concentrating re-balancing activities on essential routes). We also develop a comprehensive simulation model using a threshold-based policy to deploy the volunteers in real time, to test the effect of choice restriction on volunteers (suitably deployed) to re-position bikes. We use the Hubway system in Boston (with 60 stations) to demonstrate that using a sparse structure to concentrate the re-balancing activities of the volunteers, instead of allowing all admissible flows in the system (as in current practice), can reduce the number of re-balancing moves by a huge amount, losing only a small proportion of demand satisfied