Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines

A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

Dynamic early identification of hip replacement implants with high revision rates. Study based on the NJR data from UK during 2004-2012

BACKGROUND: Hip replacement and hip resurfacing are common surgical procedures with an estimated risk of revision of 4% over 10 year period. Approximately 58% of hip replacements will last 25 years. Some implants have higher revision rates and early identification of poorly performing hip replacement implant brands and cup/head brand combinations is vital. AIMS: Development of a dynamic monitoring method for the revision rates of hip implants. METHODS: Data on the outcomes following the hip replacement surgery between 2004 and 2012 was obtained from the National Joint Register (NJR) in the UK. A novel dynamic algorithm based on the CUmulative SUM (CUSUM) methodology with adjustment for casemix and random frailty for an operating unit was developed and implemented to monitor the revision rates over time. The Benjamini-Hochberg FDR method was used to adjust for multiple testing of numerous hip replacement implant brands and cup/ head combinations at each time point. RESULTS: Three poorly performing cup brands and two cup/ head brand combinations have been detected. Wright Medical UK Ltd Conserve Plus Resurfacing Cup (cup o), DePuy ASR Resurfacing Cup (cup e), and Endo Plus (UK) Limited EP-Fit Plus Polyethylene cup (cup g) showed stable multiple alarms over the period of a year or longer. An addition of a random frailty term did not change the list of underperforming components. The model with added random effect was more conservative, showing less and more delayed alarms. CONCLUSIONS: Our new algorithm is an efficient method for early detection of poorly performing components in hip replacement surgery. It can also be used for similar tasks of dynamic quality monitoring in healthcare

Evaluation of a combined index of optic nerve structure and function for glaucoma diagnosis

<p>Abstract</p> <p>Background</p> <p>The definitive diagnosis of glaucoma is currently based on congruent damage to both optic nerve structure and function. Given widespread quantitative assessment of both structure (imaging) and function (automated perimetry) in glaucoma, it should be possible to combine these quantitative data to diagnose disease. We have therefore defined and tested a new approach to glaucoma diagnosis by combining imaging and visual field data, using the anatomical organization of retinal ganglion cells.</p> <p>Methods</p> <p>Data from 1499 eyes of glaucoma suspects and 895 eyes with glaucoma were identified at a single glaucoma center. Each underwent Heidelberg Retinal Tomograph (HRT) imaging and standard automated perimetry. A new measure combining these two tests, the structure function index (SFI), was defined in 3 steps: 1) calculate the probability that each visual field point is abnormal, 2) calculate the probability of abnormality for each of the six HRT optic disc sectors, and 3) combine those probabilities with the probability that a field point and disc sector are linked by ganglion cell anatomy. The SFI was compared to the HRT and visual field using receiver operating characteristic (ROC) analysis.</p> <p>Results</p> <p>The SFI produced an area under the ROC curve (0.78) that was similar to that for both visual field mean deviation (0.78) and pattern standard deviation (0.80) and larger than that for a normalized measure of HRT rim area (0.66). The cases classified as glaucoma by the various tests were significantly non-overlapping. Based on the distribution of test values in the population with mild disease, the SFI may be better able to stratify this group while still clearly identifying those with severe disease.</p> <p>Conclusions</p> <p>The SFI reflects the traditional clinical diagnosis of glaucoma by combining optic nerve structure and function. In doing so, it identifies a different subset of patients than either visual field testing or optic nerve head imaging alone. Analysis of prospective data will allow us to determine whether the combined index of structure and function can provide an improved standard for glaucoma diagnosis.</p

Child abuse inventory at emergency rooms: CHAIN-ER rationale and design

<p>Abstract</p> <p>Background</p> <p>Child abuse and neglect is an important international health problem with unacceptable levels of morbidity and mortality. Although maltreatment as a cause of injury is estimated to be only 1% or less of the injured children attending the emergency room, the consequences of both missed child abuse cases and wrong suspicions are substantial. Therefore, the accuracy of ongoing detection at emergency rooms by health care professionals is highly important. Internationally, several diagnostic instruments or strategies for child abuse detection are used at emergency rooms, but their diagnostic value is still unknown. The aim of the study 'Child Abuse Inventory at Emergency Rooms' (CHAIN-ER) is to assess if active structured inquiry by emergency room staff can accurately detect physical maltreatment in children presenting at emergency rooms with physical injury.</p> <p>Methods/design</p> <p>CHAIN-ER is a multi-centre, cross-sectional study with 6 months diagnostic follow-up. Five thousand children aged 0-7 presenting with injury at an emergency room will be included. The index test - the SPUTOVAMO-R questionnaire- is to be tested for its diagnostic value against the decision of an expert panel. All SPUTOVAMO-R positives and a 15% random sample of the SPUTOVAMO-R negatives will undergo the same systematic diagnostic work up, which consists of an adequate history being taken by a pediatrician, inquiry with other health care providers by structured questionnaires in order to obtain child abuse predictors, and by additional follow-up information. Eventually, an expert panel (reference test) determines the <it>true </it>presence or absence of child abuse.</p> <p>Discussion</p> <p>CHAIN-ER will determine both positive and negative predictive value of a child abuse detection instrument used in the emergency room. We mention a benefit of the use of an expert panel and of the use of complete data. Conducting a diagnostic accuracy study on a child abuse detection instrument is also accompanied by scientific hurdles, such as the lack of an accepted reference standard and potential (non-) response. Notwithstanding these scientific challenges, CHAIN-ER will provide accurate data on the predictive value of SPUTOVAMO-R.</p

E2F1 and KIAA0191 expression predicts breast cancer patient survival

<p>Abstract</p> <p>Background</p> <p>Gene expression profiling of human breast tumors has uncovered several molecular signatures that can divide breast cancer patients into good and poor outcome groups. However, these signatures typically comprise many genes (~50-100), and the prognostic tests associated with identifying these signatures in patient tumor specimens require complicated methods, which are not routinely available in most hospital pathology laboratories, thus limiting their use. Hence, there is a need for more practical methods to predict patient survival.</p> <p>Methods</p> <p>We modified a feature selection algorithm and used survival analysis to derive a 2-gene signature that accurately predicts breast cancer patient survival.</p> <p>Results</p> <p>We developed a tree based decision method that segregated patients into various risk groups using <it>KIAA0191 </it>expression in the context of <it>E2F1 </it>expression levels. This approach led to highly accurate survival predictions in a large cohort of breast cancer patients using only a 2-gene signature.</p> <p>Conclusions</p> <p>Our observations suggest a possible relationship between <it>E2F1 </it>and <it>KIAA0191 </it>expression that is relevant to the pathogenesis of breast cancer. Furthermore, our findings raise the prospect that the practicality of patient prognosis methods may be improved by reducing the number of genes required for analysis. Indeed, our <it>E2F1/KIAA0191 </it>2-gene signature would be highly amenable for an immunohistochemistry based test, which is commonly used in hospital laboratories.</p

The Prevalence and Cost of Unapproved Uses of Top-Selling Orphan Drugs

Introduction: The Orphan Drug Act encourages drug development for rare conditions. However, some orphan drugs become top sellers for unclear reasons. We sought to evaluate the extent and cost of approved and unapproved uses of orphan drugs with the highest unit sales. Methods We assessed prescription patterns for four top-selling orphan drugs: lidocaine patch (Lidoderm) approved for post-herpetic neuralgia, modafinil (Provigil) approved for narcolepsy, cinacalcet (Sensipar) approved for hypercalcemia of parathyroid carcinoma, and imatinib (Gleevec) approved for chronic myelogenous leukemia and gastrointestinal stromal tumor. We pooled patient-specific diagnosis and prescription data from two large US state pharmaceutical benefit programs for the elderly. We analyzed the number of new and total patients using each drug and patterns of reimbursement for approved and unapproved uses. For lidocaine patch, we subcategorized approved prescriptions into two subtypes of unapproved uses: neuropathic pain, for which some evidence of efficacy exists, and non-neuropathic pain. Results: We found that prescriptions for lidocaine patch, modafinil, and cinacalcet associated with non-orphan diagnoses rose at substantially higher rates (average monthly increases in number of patients of 14.6, 1.45, and 1.58) than prescriptions associated with their orphan diagnoses (3.12, 0.24, and 0.03, respectively (p75%). Increases in lidocaine patch use for non-neuropathic pain far exceeded neuropathic pain (10.2 vs. 3.6 patients, p<0.001). Discussion In our sample, three of four top-selling orphan drugs were used more commonly for non-orphan indications. These orphan drugs treated common clinical symptoms (pain and fatigue) or laboratory abnormalities. We should continue to monitor orphan drug use after approval to identify products that come to be widely used for non-FDA approved indications, particularly those without adequate evidence of efficacy