Methods for identifying surgical wound infection after discharge from hospital: a systematic review.

Background: Wound infections are a common complication of surgery that add significantly to the morbidity of patients and costs of treatment. The global trend towards reducing length of hospital stay post-surgery and the increase in day case surgery means that surgical site infections (SSI) will increasingly occur after hospital discharge. Surveillance of SSIs is important because rates of SSI are viewed as a measure of hospital performance, however accurate detection of SSIs post-hospital discharge is not straightforward. Methods: We conducted a systematic review of methods of post discharge surveillance for surgical wound infection and undertook a national audit of methods of post-discharge surveillance for surgical site infection currently used within United Kingdom NHS Trusts. Results: Seven reports of six comparative studies which examined the validity of post-discharge surveillance methods were located; these involved different comparisons and some had methodological limitations, making it difficult to identify an optimal method. Several studies evaluated automated screening of electronic records and found this to be a useful strategy for the identification of SSIs that occurred post discharge. The audit identified a wide range of relevant post-discharge surveillance programmes in England, Scotland and Wales and Northern Ireland; however, these programmes used varying approaches for which there is little supporting evidence of validity and/or reliability. Conclusion: In order to establish robust methods of surveillance for those surgical site infections that occur post discharge, there is a need to develop a method of case ascertainment that is valid and reliable post discharge. Existing research has not identified a valid and reliable method. A standardised definition of wound infection ( e. g. that of the Centres for Disease Control) should be used as a basis for developing a feasible, valid and reliable approach to defining post discharge SSI. At a local level, the method used to ascertain post discharge SSI will depend upon the purpose of the surveillance, the nature of available routine data and the resources available

Characterization of Neutralizing Profiles in HIV-1 Infected Patients from whom the HJ16, HGN194 and HK20 mAbs were Obtained

Several new human monoclonal antibodies (mAbs) with a neutralizing potential across different subtypes have recently been described. Three mAbs, HJ16, HGN194 and HK20, were obtained from patients within the HIV-1 cohort of the Institute of Tropical Medicine (ITM). Our aim was to generate immunization antibodies equivalent to those seen in plasma. Here, we describe the selection and characterization of patient plasma and their mAbs, using a range of neutralization assays, including several peripheral blood mononuclear cell (PBMC) based assays and replicating primary viruses as well as cell line based assays and pseudoviruses (PV). The principal criterion for selection of patient plasma was the activity in an ‘extended incubation phase’ PBMC assay. Neutralizing Abs, derived from their memory B cells, were then selected by ELISA with envelope proteins as solid phase. MAbs were subsequently tested in a high-throughput HOS-PV assay to assess functional neutralization. The present study indicates that the strong profiles in the patients' plasma were not solely due to antibodies represented by the newly isolated mAbs. Although results from the various assays were divergent, they by and large indicate that neutralizing Abs to other epitopes of the HIV-1 envelope are present in the plasma and synergy between Abs may be important. Thus, the spectrum of the obtained mAbs does not cover the range of cross-reactivity seen in plasma in these carefully selected patients irrespective of which neutralization assay is used. Nevertheless, these mAbs are relevant for immunogen discovery because they bind to the recombinant glycoproteins to which the immune response needs to be targeted in vivo. Our observations illustrate the remaining challenges required for successful immunogen design and development

Genetic Crossovers Are Predicted Accurately by the Computed Human Recombination Map

Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the positions of crossovers with the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributions of crossovers with the distributions expected from the calculated recombination rate maps. Here we show that a population-averaged hotspot map computed from linkage disequilibrium data predicts well present-day genetic crossovers. We find that computed hotspot maps accurately estimate both the strength and the position of meiotic hotspots. An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations. In summary, we find that by combining several computed population-specific maps we can capture the variation in individual hotspots to generate a hotspot map that can predict almost all present-day genetic crossovers

Quantum Criticality in Heavy Fermion Metals

Quantum criticality describes the collective fluctuations of matter undergoing a second-order phase transition at zero temperature. Heavy fermion metals have in recent years emerged as prototypical systems to study quantum critical points. There have been considerable efforts, both experimental and theoretical, which use these magnetic systems to address problems that are central to the broad understanding of strongly correlated quantum matter. Here, we summarize some of the basic issues, including i) the extent to which the quantum criticality in heavy fermion metals goes beyond the standard theory of order-parameter fluctuations, ii) the nature of the Kondo effect in the quantum critical regime, iii) the non-Fermi liquid phenomena that accompany quantum criticality, and iv) the interplay between quantum criticality and unconventional superconductivity.Comment: (v2) 39 pages, 8 figures; shortened per the editorial mandate; to appear in Nature Physics. (v1) 43 pages, 8 figures; Non-technical review article, intended for general readers; the discussion part contains more specialized topic

Cytological Aspects of Pleural, Peritoneal and Pericardial Fluids From Patients With Systemic Lupus Erythematosus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74778/1/j.1365-2303.1992.tb00014.x.pd

Impact of the Kenya post-election crisis on clinic attendance and medication adherence for HIV-infected children in western Kenya

<p>Abstract</p> <p>Background</p> <p>Kenya experienced a political and humanitarian crisis following presidential elections on 27 December 2007. Over 1,200 people were killed and 300,000 displaced, with disproportionate violence in western Kenya. We sought to describe the immediate impact of this conflict on return to clinic and medication adherence for HIV-infected children cared for within the USAID-Academic Model Providing Access to Healthcare (AMPATH) in western Kenya.</p> <p>Methods</p> <p>We conducted a mixed methods analysis that included a retrospective cohort analysis, as well as key informant interviews with pediatric healthcare providers. Eligible patients were HIV-infected children, less than 14 years of age, seen in the AMPATH HIV clinic system between 26 October 2007 and 25 December 2007. We extracted demographic and clinical data, generating descriptive statistics for pre- and post-conflict antiretroviral therapy (ART) adherence and post-election return to clinic for this cohort. ART adherence was derived from caregiver-report of taking all ART doses in past 7 days. We used multivariable logistic regression to assess factors associated with not returning to clinic. Interview dialogue from was analyzed using constant comparison, progressive coding and triangulation.</p> <p>Results</p> <p>Between 26 October 2007 and 25 December 2007, 2,585 HIV-infected children (including 1,642 on ART) were seen. During 26 December 2007 to 15 April 2008, 93% (N = 2,398) returned to care. At their first visit after the election, 95% of children on ART (N = 1,408) reported perfect ART adherence, a significant drop from 98% pre-election (p < 0.001). Children on ART were significantly more likely to return to clinic than those not on ART. Members of tribes targeted by violence and members of minority tribes were less likely to return. In qualitative analysis of 9 key informant interviews, prominent barriers to return to clinic and adherence included concerns for personal safety, shortages of resources, hanging priorities, and hopelessness.</p> <p>Conclusion</p> <p>During a period of humanitarian crisis, the vulnerable, HIV-infected pediatric population had disruptions in clinical care and in medication adherence, putting children at risk for viral resistance and increased morbidity. However, unique program strengths may have minimized these disruptions.</p

Arabinose and protocatechuate catabolism genes are important for growth of Rhizobium leguminosarum biovar viciae in the pea rhizosphere

Background and aims: To form nitrogen-fixing nodules on pea roots, Rhizobium leguminosarum biovar viciae must be competitive in the rhizosphere. Our aim was to identify genes important for rhizosphere fitness. Methods: Signature-tagged mutants were screened using microarrays to identify mutants reduced for growth in pea rhizospheres. Candidate mutants were assessed relative to controls for growth in minimal medium, growth in pea rhizospheres and for infection of peas in mixed inoculants. Mutated genes were identified by DNA sequencing and confirmed by transduction. Results: Of 5508 signature-tagged mutants, microarrays implicated 50 as having decreased rhizosphere fitness. Growth tests identified six mutants with rhizosphere-specific phenotypes. The mutation in one of the genes (araE) was in an arabinose catabolism operon and blocked growth on arabinose. The mutation in another gene (pcaM), encoding a predicted solute binding protein for protocatechuate and hydroxybenzoate uptake, decreased growth on protocatechuate. Both mutants were decreased for nodule infection competitiveness with mixed inoculants, but nodulated peas normally when inoculated alone. Other mutants with similar phenotypes had mutations predicted to affect secondary metabolism. Conclusions: Catabolism of arabinose and protocatechuate in the pea rhizosphere is important for competitiveness of R.l. viciae. Other genes predicted to be involved in secondary metabolism are also important

APP controls the formation of PI(3,5)P2 vesicles through its binding of the PIKfyve complex

Phosphoinositides are signalling lipids that are crucial for major signalling events as well as established regulators of membrane trafficking. Control of endosomal sorting and endosomal homeostasis requires phosphatidylinositol-3-phosphate (PI(3)P) and phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2), the latter a lipid of low abundance but significant physiological relevance. PI(3,5)P2 is formed by phosphorylation of PI(3)P by the PIKfyve complex which is crucial for maintaining endosomal homeostasis. Interestingly, loss of PIKfyve function results in dramatic neurodegeneration. Despite the significance of PIKfyve, its regulation is still poorly understood. Here we show that the Amyloid Precursor Protein (APP), a central molecule in Alzheimer’s disease, associates with the PIKfyve complex (consisting of Vac14, PIKfyve and Fig4) and that the APP intracellular domain directly binds purified Vac14. We also show that the closely related APP paralogues, APLP1 and 2 associate with the PIKfyve complex. Whether APP family proteins can additionally form direct protein–protein interaction with PIKfyve or Fig4 remains to be explored. We show that APP binding to the PIKfyve complex drives formation of PI(3,5)P2 positive vesicles and that APP gene family members are required for supporting PIKfyve function. Interestingly, the PIKfyve complex is required for APP trafficking, suggesting a feedback loop in which APP, by binding to and stimulating PI(3,5)P2 vesicle formation may control its own trafficking. These data suggest that altered APP processing, as observed in Alzheimer’s disease, may disrupt PI(3,5)P2 metabolism, endosomal sorting and homeostasis with important implications for our understanding of the mechanism of neurodegeneration in Alzheimer’s disease

Protection in Macaques Immunized with HIV-1 Candidate Vaccines Can Be Predicted Using the Kinetics of Their Neutralizing Antibodies

A vaccine is needed to control the spread of human immunodeficiency virus type 1 (HIV-1). An in vitro assay that can predict the protection induced by a vaccine would facilitate the development of such a vaccine. A potential candidate would be an assay to quantify neutralization of HIV-1.We have used sera from rhesus macaques that have been immunized with HIV candidate vaccines and subsequently challenged with simian human immunodeficiency virus (SHIV). We compared neutralization assays with different formats. In experiments with the standardized and validated TZMbl assay, neutralizing antibody titers against homologous SHIV(SF162P4) pseudovirus gave a variable correlation with reductions in plasma viremia levels. The target cells used in the assays are not just passive indicators of virus infection but are actively involved in the neutralization process. When replicating virus was used with GHOST cell assays, events during the absorption phase, as well as the incubation phase, determine the level of neutralization. Sera that are associated with protection have properties that are closest to the traditional concept of neutralization: the concentration of antibody present during the absorption phase has no effect on the inactivation rate. In GHOST assays, events during the absorption phase may inactivate a fixed number, rather than a proportion, of virus so that while complete neutralization can be obtained, it can only be found at low doses particularly with isolates that are relatively resistant to neutralization.Two scenarios have the potential to predict protection by neutralizing antibodies at concentrations that can be induced by vaccination: antibodies that have properties close to the traditional concept of neutralization may protect against a range of challenge doses of neutralization sensitive HIV isolates; a window of opportunity also exists for protection against isolates that are more resistant to neutralization but only at low challenge doses

A possible role for Phlebotomus (Anaphlebotomus) rodhaini (Parrot, 1930) in transmission of Leishmania donovani

<p>Abstract</p> <p>Background</p> <p>Visceral leishmaniasis (VL, kala azar), caused by <it>Leishmania donovani </it>is a major health problem in Sudan and other East African countries. In this region the only proven vectors of <it>L. donovani </it>are <it>Phlebotomus orientalis </it>in eastern Sudan, Ethiopia and Upper Nile areas of Southern Sudan and <it>Phlebotomus martini </it>in Ethiopia, Kenya and Southern Sudan. In this report, we present the first evidence that <it>Phlebotomus rodhaini </it>may also play a role in maintaining transmission of <it>L. donovani </it>between animal reservoir hosts in eastern Sudan. The study was conducted in a zoonotic focus of visceral leishmaniasis in Dinder National Park, eastern Sudan, where previous work showed high infection rates of <it>L. donovani </it>in <it>P. orientalis</it>. Sand flies, captured by CDC traps were dissected and examined for infection with <it>Leishmania </it>parasites. Parasite isolates were subjected to <it>L. donovani </it>specific PCR. Field experiments were also carried out to compare efficiency of rodent baited and un-baited CDC traps in collection of <it>P. rodhaini </it>and determine its man-biting rate.</p> <p>Results</p> <p>Three female <it>P. rodhain</it>i were found infected with <it>Leishmania </it>parasites in an astonishingly small number of flies captured in three separate field trips. Two of these isolates were typed by molecular methods as <it>L. donovani</it>, while the third isolate was inoculated into a hamster that was subsequently lost. Although <it>P. rodhaini is </it>generally considered a rare species, results obtained in this study indicate that it can readily be captured by rodent-baited traps. Results of human landing collection showed that it rarely bites humans in the area.</p> <p>Conclusion</p> <p>It is concluded that <it>P. rodhaini </it>is a possible vector of <it>L. donovani </it>between animal reservoir hosts but is not responsible for infecting humans. It is suggested that the role of <it>P</it>. <it>rodhaini </it>in transmission of <it>L. donovani </it>in other zoonotic foci of visceral leishmaniasis in Africa should be re-examined.</p