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Abstract Background Much remains unknown about the effect of timing and prioritization of vaccination against pandemic (pH1N1) 2009 virus on health outcomes. We adapted a city-level contact network model to study different campaigns on influenza morbidity and mortality. Methods We modeled different distribution strategies initiated between July and November 2009 using a compartmental epidemic model that includes age structure and transmission network dynamics. The model represents the Greater Vancouver Regional District, a major North American city and surrounding suburbs with a population of 2 million, and is parameterized using data from the British Columbia Ministry of Health, published studies, and expert opinion. Outcomes are expressed as the number of infections and deaths averted due to vaccination. Results The model output was consistent with provincial surveillance data. Assuming a basic reproduction number = 1.4, an 8-week vaccination campaign initiated 2 weeks before the epidemic onset reduced morbidity and mortality by 79-91% and 80-87%, respectively, compared to no vaccination. Prioritizing children and parents for vaccination may have reduced transmission compared to actual practice, but the mortality benefit of this strategy appears highly sensitive to campaign timing. Modeling the actual late October start date resulted in modest reductions in morbidity and mortality (13-25% and 16-20%, respectively) with little variation by prioritization scheme. Conclusion Delays in vaccine production due to technological or logistical barriers may reduce potential benefits of vaccination for pandemic influenza, and these temporal effects can outweigh any additional theoretical benefits from population targeting. Careful modeling may provide decision makers with estimates of these effects before the epidemic peak to guide production goals and inform policy. Integration of real-time surveillance data with mathematical models holds the promise of enabling public health planners to optimize the community benefits from proposed interventions before the pandemic peak.

In this work, we introduce a polymer version of a previously developed silicon MEMS drop deposition tool for surface functionalization that consists of a microcantilever integrating an open fluidic channel and a reservoir. The device is fabricated by laser stereolithography, which offers the advantages of low-cost and fast prototyping. Additionally, thanks to the ability to process multiple materials, a magnetic base is incorporated into the cantilever for convenient handling and attachment to the holder of a robotized stage used for spotting. Droplets with diameters ranging from ∼50 µm to ∼300 µm are printed upon direct contact of the cantilever tip with the surface to pattern. Liquid loading is achieved by fully immersing the cantilever into a reservoir drop, where a single load results in the deposition of more than 200 droplets. The influences of the size and shape of the cantilever tip and the reservoir on the printing outcome are studied. As a proof-of-concept of the biofunctionalization capability of this 3D printed droplet dispenser, microarrays of oligonucleotides and antibodies displaying high specificity and no cross-contamination are fabricated, and droplets are deposited at the tip of an optical fiber bundle., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2023.)

Objectives: To inform next steps in pediatric diarrhea burden reduction by understanding the shifting enteropathogen landscape after rotavirus vaccine implementation., Methods: We conducted a case-control study of 1788 medically attended children younger than 5 years, with and without gastroenteritis, after universal rotavirus vaccine implementation in Peru. We tested case and control stools for 5 viruses, 19 bacteria, and parasites; calculated coinfection-adjusted attributable fractions (AFs) to determine pathogen-specific burdens; and evaluated pathogen-specific gastroenteritis severity using Clark and Vesikari scales., Results: Six pathogens were independently positively associated with gastroenteritis: norovirus genogroup II (GII) (AF 29.1, 95% confidence interval [CI]: 28.0-32.3), rotavirus (AF 8.9, 95% CI: 6.8-9.7), sapovirus (AF 6.3, 95% CI: 4.3-7.4), astrovirus (AF 2.8, 95% CI: 0.0-4.0); enterotoxigenic Escherichia coli heat stable and/or heat labile and heat stable (AF 2.4, 95% CI: 0.6-3.1), and Shigella spp. (AF 2.0, 95% CI: 0.4-2.2). Among typeable rotavirus cases, we most frequently identified partially heterotypic strain G12P[8] (54 of 81, 67%). Mean severity was significantly higher for norovirus GII-positive cases relative to norovirus GII-negative cases (Vesikari [12.7 vs 11.8; P < .001] and Clark [11.7 vs 11.4; P = .016]), and cases in the 6- to 12-month age range relative to cases in other age groups (Vesikari [12.7 vs 12.0; P = .0002] and Clark [12.0 vs 11.4; P = .0016])., Conclusions: Norovirus is well recognized as the leading cause of pediatric gastroenteritis in settings with universal rotavirus vaccination. However, sapovirus is often overlooked. Both norovirus and sapovirus contribute significantly to the severe pediatric disease burden in this setting. Decision-makers should consider multivalent vaccine acquisition strategies to target multiple caliciviruses in similar countries after successful rotavirus vaccine implementation., Competing Interests: FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose., (Some authors are military service members or employees of the US Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that “Copyright protection under this title is not available for any work of the United states Government.” Title 17 USC §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties.)

The mechanism of DNA synthesis has been inferred from static structures, but the absence of temporal information raises longstanding questions about the order of events in one of life's most central processes. Here we follow the reaction pathway of a replicative DNA polymerase using time-resolved X-ray crystallography to elucidate the order and transition between intermediates. In contrast to the canonical model, the structural changes observed in the time-lapsed images reveal a catalytic cycle in which translocation precedes catalysis. The translocation step appears to follow a push-pull mechanism where the O-O1 loop of the finger subdomain acts as a pawl to facilitate unidirectional movement along the template with conserved tyrosine residues 714 and 719 functioning as tandem gatekeepers of DNA synthesis. The structures capture the precise order of critical events that may be a general feature of enzymatic catalysis among replicative DNA polymerases.

Objectives: To describe risk factors for acquired infection during neonatal extracorporeal membrane oxygenation and to examine the predictive value of inflammatory markers in the diagnosis of infection., Methods: A retrospective study was conducted with data for patients under 30 days supported with extracorporeal membrane oxygenation from 2003 to April 2016, in a neonatal intensive care unit., Results: Our study included 160 neonatal patients, the average age of connection was 8.5 days and the duration of extracorporeal membrane oxygenation support was 9.7 days. The incidence of confirmed infection was 23%. Patients with confirmed infection present more frequently: vaginal delivery, lower birth weight, female sex, diagnosis of congenital diaphragmatic hernia, and longer duration of extracorporeal membrane oxygenation. When comparing the group of patients with confirmed infection and suspicion of infection, there were no significant differences in the inflammatory markers. When calculating the slope for each one, the difference in white blood cell count slope 72 h before the infection is significant; in patients with confirmed infection, the count of white blood cell increases (slope: 0.25), versus the group of patients with suspected infection in whom the count decreases (slope: -0.39). No differences were found in other variables., Conclusion: Our study describes that the factors that increase the risk of infection are lower birth weight, vaginal birth, duration of extracorporeal membrane oxygenation, and a positive trend of white blood cell 72 h prior to infection/suspicion. Further studies are necessary to include or definitively rule out the use of these factors and the biomarkers as predictors of infection in neonatal patients supported with extracorporeal membrane oxygenation.

Campylobacter jejuni is the leading bacterial cause of diarrhea worldwide. A capsular polysaccharide (CPS) conjugate vaccine is under development and requires determination of the valency. However, distribution of CPS types circulating globally is presently poorly described. We aimed to determine whether CPS type distribution in Peru differs from that in other endemic regions. We used a multiplex polymerase chain reaction (PCR) assay for the detection of CPS encoding genes capable of distinguishing all 35 CPS types on Campylobacter isolates in two prospective communities based studies conducted in cohorts of children less than 59 months of age in Peru. Results showed that CPS type HS4 complex was the most prevalent, followed by HS3 complex and HS15. Differences in CPS type for symptomatology were not statistically significant. Most subjects demonstrated repeated infections over time with different CPS types, suggesting that CPS types may confer of a level of homologous protective immunity. In this dataset, some differences in CPS type distribution were observed in comparison to other low-middle income countries. Further studies need to be conducted in endemic areas to increase our knowledge of CPS type distribution and guide vaccine development.

Introduction: OA is currently the fifth leading cause of adult disability, its prevalence increases from age 40. Viscosupplementation is a treatment for the early stages of knee OA., Objective: To compare efficacy and quality of life in patients with symptomatic gonartrosis, treated with high and low molecular weight hyaluronic acid., Material and Methods: Analytical, retrospective, cross-sectional, observational study of clinical records of patients diagnosed with grade II and grade III gonarthrosis, October 2017 to June 2018, treated with viscosupplementation with high molecular weight hyaluronic acid or low molecular weight; WOMAC quality of life and scale were analyzed prior to the first application and tracked at two, four and six months., Results: 194 patients, aged between 30 to 87 years (promedio 61.85; SD = 11.3); 134 women (69.1%), 60 men (30.9%). In both groups the evolution was towards improvement, with a decrease in the WOMAC score, with no significant difference between groups. The WOMAC score had a minimum increase after 6 months of application in both groups, which is interpreted as decreasing the therapeutic effect. Two patients had localized minimal adverse reactions which were resolved with general measures., Conclusion: Hyaluronic acid in both presentations, high and low molecular weight, are effective in the treatment of symptomatic goonarthrosis without difference to molecular weight.

Introduction: The coxarthrosis has incidence of 88 cases per 100,000 people/year and symptomatic prevalence of 16% men and 6% women aged 65-74 years and increases with age. It is a growing public health disease. Total hip arthroplasty (THA) has become the most successful procedure to increase the quality of life of patients with coxarthrosis. Our objective was to determine the claudication, quality of life and functional results of THA through minimal invasive approach in patients with primary coxarthrosis., Material and Methods: Prospective longitudinal study in patients with unilateral primary coxarthrosis postop of THA with minimally invasive approach from March 2015-February 2016, each patient was analyzed with quality of Life instrument (WOMAC), Functional test for coxarthrosis (HHS) and functional test in patients with hip surgery (OHS) with follow-up of one year., Results: We included 21 patients, 17 female and 4 males corresponding to 80.95% and 19.05% respectively, average age of 59.95 years (ED = 9.64), with excellent functional results to one year according to HHS and OHS, quality of life high in 100% of cases according to WOMAC, with claudication rate of 4.76%., Discussion: The minimal invasive approach is a reproducible surgical technique, with excellent functional results, low claudication rate and high quality of life in postoperative patients of primary ATC at only one year of follow-up.

Objectives: To draw evidence-based conclusions about the epidemiology, drivers, and management of diabetes in Panama based on a literature review and original analyses of large databases., Methods: A search about diabetes in Panama was conducted through PubMed. We used the final reports of 2 studies: the first Survey of Health and Life Quality, 2007, and the first Survey of Risk Factors Associated to Cardiovasular Diseases, 2010-2011, conducted in Panama and analyzed the databases. We reviewed the approach adopted by the Panamanian Social Security institution and the diabetes national guidelines published by the Panamanian Ministry of Health., Findings: The prevalence of diabetes, as estimated in 1 database (ENSCAVI), was 5.4% (4.3% men; 6.0% women; OR = 1.41 [confidence interval 1.26-1.59]; P < 0.0001), with the highest prevalence in urbanized regions. In another database (PREFREC), prevalence was 9.5% (10.3% men and 9.1% women), again higher in urbanized regions, but also in males, older adults, and Afro-Panamanians. Obesity, abdominal obesity, physical inactivity, family history of diabetes, high blood pressure, and triglycerides ≥ 150 mg/dL were associated as risk factors for diabetes in both genders (P < 0.0001). Total cholesterol ≥ 200 mg/dL and high-density lipoprotein cholesterol < 40 mg/dL were risk factors in men (P < 0.0001). In the last 5 years, diabetes was ranked between the sixth and fifth cause of death in Panama. In response, the Panamanian Social Security created the "Program for Prevention and Control of Diabetes" to strengthen primary health care., Conclusions: Diabetes is a serious national public health threat in Panama. To address this problem in a public health modality, information from large databases was analyzed and presented to the Panamanian Ministry of Health to prompt constructive policy change to enhance diabetes prevention., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Immunisation is the sixth most commonly managed problem in general practice in Australia. This paper provides an overview of its management in general practice.

The most cost-effective method to measure the morbidity managed and treatments provided in general practice is from records of a cluster of consultations (encounters) from each general practitioner (GP) in a random sample. A cluster sampling method is proposed for future surveys for analysis of encounter-based general practice data. The sample sizes needed to measure the most common problems managed and drugs prescribed were estimated using ratio-estimator models for cluster sample surveys. Morbidity and treatment rates were estimated from the Australian Morbidity and Treatment Survey in General Practice 1990-1991 (AMTS). The 20 most common problems in the AMTS were managed at estimated rates of 1.5 to 9.5 per 100 encounters. The 20 most common drugs were prescribed at estimated rates of 0.7 to 3.6 per 100 problems. These rates were used to determine precision as a percentage of each true value for future surveys, that is, as relative precision. If we want to be 95 per cent confident that these rates will be within 5 per cent of each true rate, sample sizes of 552 to 5675 GPs are needed. If we fix the sample size at 1000 GPs, relative precision lies within 12 per cent of these rates. If the sample size is increased to 1500 GPs, relative precision improves only marginally. The differences in sample size for each of the most frequent morbidity and treatment data are largely due to their variable distributions and relatively infrequent occurrence in general practice. A sample size of 1000 GPs will enable measurement of the most common morbidity and treatments at 95 per cent confidence.

Arthritis is the ninth most commonly managed problem in general practice in Australia. This paper provides an overview of its management in general practice and draws some comparisons with an earlier study.

Osteoarthritis is the fourth most commonly managed problem in general practice in Australia. This paper provides an overview of its management in general practice.

A landscape approach using remote sensing and geographic information system (GIS) technologies was developed to discriminate between villages at high and low risk for malaria transmission, as defined by adult Anopheles albimanus abundance. Satellite data for an area in southern Chiapas, Mexico were digitally processed to generate a map of landscape elements. The GIS processes were used to determine the proportion of mapped landscape elements surrounding 40 villages where An. albimanus abundance data had been collected. The relationships between vector abundance and landscape element proportions were investigated using stepwise discriminant analysis and stepwise linear regression. Both analyses indicated that the most important landscape elements in terms of explaining vector abundance were transitional swamp and unmanaged pasture. Discriminant functions generated for these two elements were able to correctly distinguish between villages with high and low vector abundance, with an overall accuracy of 90%. Regression results found both transitional swamp and unmanaged pasture proportions to be predictive of vector abundance during the mid-to-late wet season. This approach, which integrates remotely sensed data and GIS capabilities to identify villages with high vector-human contact risk, provides a promising tool for malaria surveillance programs that depend on labor-intensive field techniques. This is particularly relevant in areas where the lack of accurate surveillance capabilities may result in no malaria control action when, in fact, directed action is necessary. In general, this landscape approach could be applied to other vector-borne diseases in areas where 1) the landscape elements critical to vector survival are known and 2) these elements can be detected at remote sensing scales.

Sprains and strains were the eighth most commonly managed problem in general practice in Australia. This paper provides an overview of their management in general practice.

Acute bronchitis is the fifth most commonly managed problem in general practice in Australia. This paper provides an overview of its management in general practice and compares the results with those of an earlier study.

Upper respiratory tract infection is the second most frequently managed problem in general practice in Australia. This paper provides an overview of its management in general practice and compares the results with those of an earlier study.

Hypertension is the most frequently managed problem in general practice in Australia. This paper provides an overview of its management in general practice and draws some comparisons with an earlier study.

Spatial and seasonal variations on Anopheles albimanus larval densities and their plant associations were investigated in larval habitats in southern Mexico between April 1989 and May 1990. Thirty-four plant groups were dominant in larval habitats. Dense larval populations were associated with 3 genera of plants, Cynodon, Echinocloa and Fimbristylis and no larvae were found in habitats with Salvinia and Rhizophora. Low significant positive or negative associations were documented with the other 12 plant genera. Larval habitats were classified according to the morphology of their dominant plants. Higher larval densities were observed in the groups characterized by relatively short emergent vegetation. The distribution of habitat-types within 5 identified vegetation units showed a significantly dependent relationship. For the entire study period, highest larval densities were detected in flooded pasture/grassland vegetation units. For all vegetation units, higher larval densities were found when the dominant plant type covered between 25-50% of the breeding site. The integration of data from habitat-types into vegetation units did not result in loss of information.