Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing

Airway infection by the Gram-positive pathogen Streptococcus pneumoniae (Sp) leads to recruitment of neutrophils but limited bacterial killing by these cells. Co-colonization by Sp and a Gram-negative species, Haemophilus influenzae (Hi), provides sufficient stimulus to induce neutrophil and complement-mediated clearance of Sp from the mucosal surface in a murine model. Products from Hi, but not Sp, also promote killing of Sp by ex vivo neutrophil-enriched peritoneal exudate cells. Here we identify the stimulus from Hi as its peptidoglycan. Enhancement of opsonophagocytic killing was facilitated by signaling through nucleotide-binding oligomerization domain-1 (Nod1), which is involved in recognition of γ-D-glutamyl-meso-diaminopimelic acid (meso-DAP) contained in cell walls of Hi but not Sp. Neutrophils from mice treated with Hi or compounds containing meso-DAP, including synthetic peptidoglycan fragments, showed increased Sp killing in a Nod1-dependent manner. Moreover, Nod1-/- mice showed reduced Hi-induced clearance of Sp during co-colonization. These observations offer insight into mechanisms of microbial competition and demonstrate the importance of Nod1 in neutrophil-mediated clearance of bacteria in vivo

Cost-eff ectiveness of surgery and its policy implications for global health: a systematic review and analysis

Background The perception of surgery as expensive and complex might be a barrier to its widespread acceptance in global health eff orts. We did a systematic review and analysis of cost-eff ectiveness studies that assess surgical interventions in low-income and middle-income countries to help quantify the potential value of surgery. Methods We searched Medline for all relevant articles published between Jan 1, 1996 and Jan 31, 2013, and searched the reference lists of retrieved articles. We converted all results to 2012 US$. We extracted cost-eff ectiveness ratios (CERs) and appraised economic assessments for their methodological quality using the 10-point Drummond checklist. Findings Of the 584 identifi ed studies, 26 met full inclusion criteria. Together, these studies gave 121 independent CERs in seven categories of surgical interventions. The median CER of circumcision ($13·78 per disability-adjusted life year [DALY]) was similar to that of standard vaccinations ($12·96–25·93 per DALY) and bednets for malaria prevention ($6·48–22·04 per DALY). Median CERs of cleft lip or palate repair ($47·74 per DALY), general surgery ($82·32 per DALY), hydrocephalus surgery ($108·74 per DALY), and ophthalmic surgery ($136 per DALY) were similar to that of the BCG vaccine ($51·86–220·39 per DALY). Median CERs of caesarean sections ($315·12 per DALY) and orthopaedic surgery ($381·15 per DALY) are more favourable than those of medical treatment for ischaemic heart disease ($500·41–706·54 per DALY) and HIV treatment with multidrug antiretroviral therapy ($453·74–648·20 per DALY). Interpretation Our fi ndings suggest that many essential surgical interventions are cost-eff ective or very cost-eff ective in resource-poor countries. Quantifi cation of the economic value of surgery provides a strong argument for the expansion of global surgery’s role in the global health movement. However, economic value should not be the only argument for resource allocation—other organisational, ethical, and political arguments can also be made for its inclusion

Perspectives in quality: designing the WHO Surgical Safety Checklist

The World Health Organization's Patient Safety Programme created an initiative to improve the safety of surgery around the world. In order to accomplish this goal the programme team developed a checklist with items that could and, if at all possible, should be practised in all settings where surgery takes place. There is little guidance in the literature regarding methods for creating a medical checklist. The airline industry, however, has more than 70 years of experience in developing and using checklists. The authors of the WHO Surgical Safety Checklist drew lessons from the aviation experience to create a safety tool that supports essential clinical practice. In order to inform the methodology for development of future checklists in health care, we review how we applied lessons learned from the aviation experience in checklist development to the development of the Surgical Safety Checklist and also discuss the differences that exist between aviation and medicine that impact the use of checklists in health car

Timing and cost of scaling up surgical services in low-income and middle-income countries from 2012 to 2030 : a modelling study

Background: Given the large burden of surgical conditions and the crosscutting nature of surgery, scale-up of basic surgical services is crucial to health-system strengthening. The Lancet Commission on Global Surgery proposed that, to meet populations' needs, countries should achieve 5000 major operations per 100 000 population per year. We modelled the possible scale-up of surgical services in 88 low-income and middle-income countries with a population greater than 1 million from 2012 to 2030 at various rates and quantified the associated costs. Methods: Major surgery includes any intervention within an operating room involving tissue manipulation and anaesthesia. We used estimates for the number of major operations achieved per country annually and the number of operating rooms per region, and data from Mongolia and Mexico for trends in the number of operations. Unit costs included a cost per operation, proxied by caesarean section cost estimates; hospital construction data were used to estimate cost per operating room construction. We determined the year by which each country would achieve the Commission's target. We modelled three scenarios for the scale-up rate: actual rates (5·1% per year) and two "aspirational" rates, the rates achieved by Mongolia (8·9% annual) and Mexico (22·5% annual). We subsequently estimated the associated costs. Findings: About half of the 88 countries would achieve the target by 2030 at actual rates of improvements, with up to two-thirds if the rate were increased to Mongolian rates. We estimate the total costs of achieving scale-up at US$300-420 billion (95% UI 190-600 billion) over 2012-30, which represents 4-8% of total annual health expenditures among low-income and lower middle-income countries and 1% among upper middle-income countries. Interpretation: Scale-up of surgical services will not reach the target of 5000 operations per 100 000 by 2030 in about half of low-income and middle-income countries without increased funding, which countries and the international community must seek to achieve expansion of quality surgical services

Optically induced coherent intra-band dynamics in disordered semiconductors

On the basis of a tight-binding model for a strongly disordered semiconductor with correlated conduction- and valence band disorder a new coherent dynamical intra-band effect is analyzed. For systems that are excited by two, specially designed ultrashort light-pulse sequences delayed by tau relatively to each other echo-like phenomena are predicted to occur. In addition to the inter-band photon echo which shows up at exactly t=2*tau relative to the first pulse, the system responds with two spontaneous intra-band current pulses preceding and following the appearance of the photon echo. The temporal splitting depends on the electron-hole mass ratio. Calculating the population relaxation rate due to Coulomb scattering, it is concluded that the predicted new dynamical effect should be experimentally observable in an interacting and strongly disordered system, such as the Quantum-Coulomb-Glass.Comment: to be published in Physical Review B15 February 200