Laboratory Diagnosis of Mycobacterial Infections: New Tools and Lessons Learned

Even in the 21st century, tuberculosis continues to be a problem. Although the number of cases continues gradually to decrease in the United States, cases get more difficult to treat, specifically those that are multiple-drug resistant. Infection of one-third of the world's population ensures that tuberculosis will not disappear in the near future. In light of this, it will be useful to know the goals for the health care system and how these goals may be accomplished. Laboratory testing in the mycobacteriology field is experiencing more changes today than ever before. Determining what assays will be most useful to the clinician is a challenge, and acceptance of the new technology by the medical community an even greater one. Clinicians must use the best available resources to determine the most appropriate care for their patients and work together with the laboratory to ensure that the communication channels are open. This review focuses on current state-of-the-art resources useful for accurate and rapid laboratory diagnosis of mycobacterial infection

Investigating the properties of granulation in the red giants observed by Kepler

More than 1000 red giants have been observed by NASA/Kepler mission during a nearly continuous period of ~ 13 months. The resulting high-frequency resolution (< 0.03 muHz) allows us to study the granulation parameters of these stars. The granulation pattern results from the convection motions leading to upward flows of hot plasma and downward flows of cooler plasma. We fitted Harvey-like functions to the power spectra, to retrieve the timescale and amplitude of granulation. We show that there is an anti-correlation between both of these parameters and the position of maximum power of acoustic modes, while we also find a correlation with the radius, which agrees with the theory. We finally compare our results with 3D models of the convection.Comment: 4 pages, 1 figure. To appear in the ASP proceedings of "The 61st Fujihara seminar: Progress in solar/stellar physics with helio- and asteroseismology", 13th-17th March 2011, Hakone, Japa

Seismic analysis of four solar-like stars observed during more than eight months by Kepler

Having started science operations in May 2009, the Kepler photometer has been able to provide exquisite data of solar-like stars. Five out of the 42 stars observed continuously during the survey phase show evidence of oscillations, even though they are rather faint (magnitudes from 10.5 to 12). In this paper, we present an overview of the results of the seismic analysis of 4 of these stars observed during more than eight months.Comment: 5 pages, 1 figure. To appear in the ASP proceedings of "The 61st Fujihara seminar: Progress in solar/stellar physics with helio- and asteroseismology", 13th-17th March 2011, Hakone, Japa

Assessing hospitals' clinical risk management: Development of a monitoring instrument

<p>Abstract</p> <p>Background</p> <p>Clinical risk management (CRM) plays a crucial role in enabling hospitals to identify, contain, and manage risks related to patient safety. So far, no instruments are available to measure and monitor the level of implementation of CRM. Therefore, our objective was to develop an instrument for assessing CRM in hospitals.</p> <p>Methods</p> <p>The instrument was developed based on a literature review, which identified key elements of CRM. These elements were then discussed with a panel of patient safety experts. A theoretical model was used to describe the level to which CRM elements have been implemented within the organization. Interviews with CRM practitioners and a pilot evaluation were conducted to revise the instrument. The first nationwide application of the instrument (138 participating Swiss hospitals) was complemented by in-depth interviews with 25 CRM practitioners in selected hospitals, for validation purposes.</p> <p>Results</p> <p>The monitoring instrument consists of 28 main questions organized in three sections: 1) Implementation and organizational integration of CRM, 2) Strategic objectives and operational implementation of CRM at hospital level, and 3) Overview of CRM in different services. The instrument is available in four languages (English, German, French, and Italian). It allows hospitals to gather comprehensive and systematic data on their CRM practice and to identify areas for further improvement.</p> <p>Conclusions</p> <p>We have developed an instrument for assessing development stages of CRM in hospitals that should be feasible for a continuous monitoring of developments in this important area of patient safety.</p

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Laboratory Diagnosis of Mycobacterial Infections: New Tools and Lessons Learned

Even in the 21st century, tuberculosis continues to be a problem. Although the number of cases continues gradually to decrease in the United States, cases get more difficult to treat, specifically those that are multiple-drug resistant. Infection of one-third of the world's population ensures that tuberculosis will not disappear in the near future. In light of this, it will be useful to know the goals for the health care system and how these goals may be accomplished. Laboratory testing in the mycobacteriology field is experiencing more changes today than ever before. Determining what assays will be most useful to the clinician is a challenge, and acceptance of the new technology by the medical community an even greater one. Clinicians must use the best available resources to determine the most appropriate care for their patients and work together with the laboratory to ensure that the communication channels are open. This review focuses on current state-of-the-art resources useful for accurate and rapid laboratory diagnosis of mycobacterial infection