Managing healthcare budgets in times of austerity: the role of program budgeting and marginal analysis

Given limited resources, priority setting or choice making will remain a reality at all levels of publicly funded healthcare across countries for many years to come. The pressures may well be even more acute as the impact of the economic crisis of 2008 continues to play out but, even as economies begin to turn around, resources within healthcare will be limited, thus some form of rationing will be required. Over the last few decades, research on healthcare priority setting has focused on methods of implementation as well as on the development of approaches related to fairness and legitimacy and on more technical aspects of decision making including the use of multi-criteria decision analysis. Recently, research has led to better understanding of evaluating priority setting activity including defining ‘success’ and articulating key elements for high performance. This body of research, however, often goes untapped by those charged with making challenging decisions and as such, in line with prevailing public sector incentives, decisions are often reliant on historical allocation patterns and/or political negotiation. These archaic and ineffective approaches not only lead to poor decisions in terms of value for money but further do not reflect basic ethical conditions that can lead to fairness in the decision-making process. The purpose of this paper is to outline a comprehensive approach to priority setting and resource allocation that has been used in different contexts across countries. This will provide decision makers with a single point of access for a basic understanding of relevant tools when faced with having to make difficult decisions about what healthcare services to fund and what not to fund. The paper also addresses several key issues related to priority setting including how health technology assessments can be used, how performance can be improved at a practical level, and what ongoing resource management practice should look like. In terms of future research, one of the most important areas of priority setting that needs further attention is how best to engage public members

Water on Oxide Surfaces

Most oxidE.. surfaces interact with ambient water vapor to form a layer of chemisorbed hydroxyls. Physical adsorption of multilayer water readily starts by hydrogen bonding onto the hydroxyl array. The normally hydrophilic surface 0£ silica can be modified by heating to produce a predominantly hydrophobic matrix which contains but a few isolated hydrophilic sites, around which water adsorbs in clusters. The authors\u27 results on both hydrophilic and hydrophobed oxides are discussed and compared to results in the literature

PuLSE:Quality control and quantification of peptide sequences explored by phage display libraries

The design of highly diverse phage display libraries is based on assumption that DNA bases are incorporated at similar rates within the randomized sequence. As library complexity increases and expected copy numbers of unique sequences decrease, the exploration of library space becomes sparser and the presence of truly random sequences becomes critical. We present the program PuLSE (Phage Library Sequence Evaluation) as a tool for assessing randomness and therefore diversity of phage display libraries. PuLSE runs on a collection of sequence reads in the fastq file format and generates tables profiling the library in terms of unique DNA sequence counts and positions, translated peptide sequences, and normalized 'expected' occurrences from base to residue codon frequencies. The output allows at-a-glance quantitative quality control of a phage library in terms of sequence coverage both at the DNA base and translated protein residue level, which has been missing from toolsets and literature. The open source program PuLSE is available in two formats, a C++ source code package for compilation and integration into existing bioinformatics pipelines and precompiled binaries for ease of use

Factors Promoting or Preventing Caregivers from Allowing Pediatric Participation in Research

Introduction The likelihood of a child participating in a clinical trial is mostly independent of the child’s willingness to participate; children’s lack of autonomy obliges parental involvement, which is concurrently conditional to parental understanding, trust and endorsement of the research study. Objectives To identify potential predictors for allowing children to participate in clinical studies and to evaluate if motivators that promote or prevent parental support of children to participate in clinical studies differed according to racial/ethnic categorization. Methods A stratified sample of 1,057 caregivers of children 1-18 years old who in 2015 resided in South Florida’s Miami-Dade, Broward, and Palm Beach counties were included in the study. Pediatric research participation was analyzed by exploratory unadjusted weighted multinomial association tests. Results There were different reasons for which caregivers will allow or reject children participation in clinical research. The sex of the respondent [OR = 2.48 (1.58 - 3.90)], difficulties accessing health care access [OR = 2.77 (1.60 – 4.80)], and child’s underweight status [OR: 3.22 (1.90 – 5.47)] significantly differed between those very likely and unlikely to participate. Conclusions Caregivers decision to allow children to participate or not in clinical research differ according to race/ethnic classification, gender of caregivers, and weight status of the child

Increased metabolic rate of hauled-out harbor seals (Phoca vitulina) during the molt

Harbor seals (Phoca vitulina) live in cold temperate or polar seas and molt annually, renewing their fur over a period of approximately 4 wk. Epidermal processes at this time require a warm skin; therefore, to avoid an excessive energy cost at sea during the molt, harbor seals and many other pinnipeds increase the proportion of time they are hauled out on land. We predicted that metabolic rate during haul-out would be greater during the molt to sustain an elevated skin temperature in order to optimize skin and hair growth. To examine this, we measured post-haul-out oxygen consumption (V˙O2) in captive harbor seals during molt and postmolt periods. We recorded greater V˙O2 of seals while they were molting than when the molt was complete. Post-haul-out V˙O2 increased faster and reached a greater maximum during the first 40 min. Thereafter, V˙O2 decreased but still remained greater, suggesting that while metabolic rate was relatively high throughout haul-outs, it was most pronounced in the first 40 min. Air temperature, estimated heat increment of feeding, and mass also explained 15.5% of V˙O2 variation over 180 min after haul-out, suggesting that the environment, feeding state, and body size influenced the metabolic rate of individual animals. These results show that molting seals have greater metabolic rates when hauled out, especially during the early stages of the haul-out period. As a consequence, human disturbance that changes the haul-out behavior of molting seals will increase their energy costs and potentially extend the duration of the molt.Peer reviewe

The genome of the sea urchin Strongylocentrotus purpuratus

We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes

Resolvin E1 Reverses Experimental Periodontitis and Dysbiosis

Periodontitis is a biofilm-induced inflammatory disease characterized by dysbiosis of the commensal periodontal microbiota. It is unclear how natural regulation of inflammation affects the periodontal biofilm. Promoters of active resolution of inflammation including Resolvin E1 (RvE1) effectively treat inflammatory periodontitis in animal models. The goals of this study were 1) to compare periodontal tissue gene expression in different clinical conditions, 2) to determine the impact of local inflammation on the composition of subgingival bacteria, and 3) to understand how inflammation impacts these changes. Two clinically-relevant experiments were performed in rats: prevention and treatment of ligature-induced periodontitis with RvE1 topical treatment. The gingival transcriptome was evaluated by RNA-seq sequencing of mRNA. The composition of the subgingival microbiota was characterized by 16S rDNA sequencing. Periodontitis was assessed by bone morphometric measurements and histomorphometry of block sections. H&E and, tartrate resistant acid phosphatase staining were used to characterize and quantify inflammatory changes. RvE1 treatment prevented bone loss in ligature induced periodontitis. Osteoclast density and inflammatory cell infiltration in the RvE1 groups were lower than those in the placebo group. RvE1 treatment reduced expression of inflammation-related genes returning the expression profile to one more similar to health. Treatment of established periodontitis with RvE1 reversed bone loss, reversed inflammatory gene expression and reduced osteoclast density. Assessment of the rat subgingival microbiota after RvE1 treatment revealed marked changes in both prevention and treatment experiments. The data suggest that modulation of local inflammation has a major role in shaping the composition of the subgingival microbiota

Using Near Infrared Reflectance Spectroscopy (NIRS) to predict the protein and energy digestibility of lupin kernel meals when fed to rainbow trout, Oncorhynchus mykiss

This study examined the potential of using near infrared spectroscopy (NIRS) to predict the nutrient composition, energy density and the digestible protein and digestible energy values of lupin kernel meals when fed to rainbow trout. A series of 136 lupin kernel meals were assessed for their protein and energy digestibilities using the diet-substitution approach in a series of 10 experiments over a 6-year period from 2002 to 2008. Two reference diets were also included in each experiment. Minimal variance in the digestibility parameters of both reference diets was observed among the experiments ensuring that there was a high degree of robustness in the across-experiment evaluations. The same lupin kernel meal samples were also scanned using a diode array near infrared spectrophotometer (DA-NIRS). The spectra obtained by the DA-NIRS were chemometrically calibrated against both the chemical composition and the digestible value data using multivariate analysis software. The cross validation tests used in this study provide a valid indication of the potential to predict the nutrient composition, energy value and digestible protein and energy values of the lupin kernel meals as used in diets for rainbow trout. That the standard errors of cross validation (SECV) of the parameters investigated were generally commensurate with the cross trial variation seen in the reference sample indicating robust calibrations for the two target parameters of digestible protein and digestible energy. Therefore this study demonstrates that within one raw material type that not only does significant variability in the digestible value of the raw materials exist, but that it is possible to use NIRS technology to provide rapid estimates of the digestible value of those raw materials in near real-time. © 2014 John Wiley & Sons Ltd

Sand fly saliva reprograms skin fibroblasts to enhance arbovirus infection

Arbovirus transmission by sand flies is a growing public health concern, yet the early skin events shaping infection outcomes remain undefined. We establish a mouse model of Toscana virus (TOSV) infection that incorporates sand fly salivary factors to mimic natural transmission. Saliva from two distinct sand fly genera significantly enhanced infection and promoted neurological signs and joint inflammation, recapitulating key features of human TOSV disease. In the skin, dermal macrophages and fibroblasts were the main infected cell types, but only fibroblasts generated infectious virus. Saliva reprogrammed fibroblasts into a wound-healing state permissive to viral replication, driving local viral amplification, systemic spread, and thereby clinical disease. These findings identify skin fibroblasts as central determinants of host susceptibility and reveal that sand fly saliva actively remodels the skin to exacerbate viral pathogenesis. This work redefines the skin's role in sand fly-transmitted infection and highlights new targets for therapeutic and vaccine development.</p