Everything You Need to Know about Grants: Beginning, Middle and End

“Everything You Need to Know about Grants: Beginning, Middle and End” was a 90-minute session presented at the Society of California Archivists Annual General Meeting in Berkeley, CA, on April 13, 2013. As a part of the archival community, many of us know that grants are an excellent way to reduce backlogs or accomplish projects we don\u27t have the resources to tackle. However, what many of us may not know is how much work goes into successfully implementing and completing a grant. The purpose of this session was to assemble a group of individuals who have been involved in various aspects of the grant application and implementation process to share their expertise with the archival community. The session utilized a question and answer format with a moderator asking pre-arranged questions. This article provides excerpts from the panelists’ responses

Diagnosis, natural course and treatment outcomes of groove pancreatitis

Background: Groove pancreatitis (GP) is a rare form of chronic pancreatitis with limited data on its diagnostics and treatment outcomes. The aim of this study was to assess its diagnostics, natural course, and treatment options. Methods: The study is a retrospective population-based study from Southern Finland, including all patients with suspected GP between January 2005 and December 2015. Two certified gastrointestinal radiologists re-reviewed the imaging studies. The radiological re-review, clinical judgment, and final histopathology confirmed the GP diagnoses. Results: Out of 67 patients with possible GP, 39 patients were considered to have high radiological certainty of GP. Out of these 39, five patients had cancer instead. Thirty-three patients with confirmed GP formed the final study cohort. Patients with GP were mostly middle-aged (median 55 years) men. All had at least moderate alcohol consumption. No intervention was needed in 14 patients. In five-year follow-up all conservatively treated patients became asymptomatic, while 10 out of 16 patients undergoing at least one intervention were asymptomatic at five years. Conclusion: The radiological diagnosis of GP is difficult, and a low threshold for cancer suspicion should be kept. Symptoms of GP decrease with time and suggest conservative treatment as the first-line option.Peer reviewe

Framing the discussion of microorganisms as a facet of social equity in human health

What do “microbes” have to do with social equity? These microorganisms are integral to our health, that of our natural environment, and even the “health” of the environments we build. The loss, gain, and retention of microorganisms—their flow between humans and the environment—can greatly impact our health. It is well-known that inequalities in access to perinatal care, healthy foods, quality housing, and the natural environment can create and arise from social inequality. Here, we focus on the argument that access to beneficial microorganisms is a facet of public health, and health inequality may be compounded by inequitable microbial exposure

Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer : An Open-label Phase 1 Study

Background: ODM-201 is a novel second-generation androgen receptor inhibitor for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Objective: To evaluate the pharmacokinetics of ODM-201 tablet products and preliminary long-term safety, tolerability, and antitumor activity of ODM-201 in chemotherapy-naive men with mCRPC. Design, setting, and participants: Thirty patients were enrolled in this open-label phase 1 trial. Patients received a single 600-mg dose of ODM-201 in capsules with food and one 600-mg dose of ODM-201 tablet product (TabA or TabB) with food and in the fasted state in a random order. In the extension, patients received 600 mg twice daily ODM-201 taken with food in capsules. Outcome measurements and statistical analysis: We analyzed the pharmacokinetics of ODM-201 tablet formulations. Safety and tolerability were assessed until disease progression or an intolerable adverse event (AE). Antitumor activity was assessed by prostate-specific antigen (PSA) levels and imaging. Results and limitations: The capsule: TabA ratio of area under the concentration-time curve from time zero to the last sample at 48 h was 1.06 (90% confidence interval [CI], 0.91-1.24); the capsule: TabB ratio was 0.97 (90% CI, 0.82-1.14). At week 12, 25 of 30 patients (83%) had a PSA response (>= 50% reduction from baseline). Median time to radiographic progression was 66 wk (95% CI, 41-79). Most common AEs were fatigue (n = 4 [13%]) and nausea (n = 4 [13%]). Conclusions: The study showed that the tablet formulation of ODM-201 had similar pharmacokinetics compared with the capsule. Treatment with a 600-mg twice daily dose of ODM-201 provided anticancer activity and was well tolerated in men with chemotherapy-naive mCRPC. Patient summary: The findings of this study showed that ODM-201 is well tolerated and provided antitumor activity in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC) and that the 300-mg tablet formulation can be used in further clinical studies. A phase 3 trial with ODM-201 600 mg twice daily in patients with non-mCRPC is ongoing. (C) 2015 European Association of Urology. Published by Elsevier B.V.Peer reviewe

Systematic Reviews and Meta-Analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery

\ua9 2024 Lippincott Williams and Wilkins. All rights reserved.Objective: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. Background: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. Methods: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. Results: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. Conclusions: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding

Plant diversity greatly enhances weed suppression in intensively managed grasslands

Weed suppression was investigated in a field experiment across 31 international sites. The study included 15 plant communities at each site, based on two grasses and two legumes, each sown in monoculture and 11 four-species mixtures varying in the relative proportions of the four species. At each site, one grass and one legume species was selected as fast establishing and the other two species were selected for persistence. Average weed biomass in mixtures over the whole experiment was 52% less (95% confidence interval, 30 to 75%) than in the most suppressive monoculture (transgressive suppression). Transgressive suppression of weed biomass persisted over each year for each mixture. Weed biomass was consistently low and relatively similar across all mixtures and years. Average sown species biomass was greater in all mixtures than in any monoculture. The suppressive effect of sown forage species on weeds in mixtures was achieved without any herbicide use. At each site, weed biomass for almost every mixture was lower than the average across the four monocultures. The average proportion of weed biomass in mixtures was less than in the most suppressive monoculture in two thirds of sites. Mixtures outyielded monocultures, and mixture yield comprised far lower weed biomass

Yeast : the soul of beer’s aroma—a review of flavour-active esters and higher alcohols produced by the brewing yeast

Among the most important factors influencing beer quality is the presence of well-adjusted amounts of higher alcohols and esters. Thus, a heavy body of literature focuses on these substances and on the parameters influencing their production by the brewing yeast. Additionally, the complex metabolic pathways involved in their synthesis require special attention. More than a century of data, mainly in genetic and proteomic fields, has built up enough information to describe in detail each step in the pathway for the synthesis of higher alcohols and their esters, but there is still place for more. Higher alcohols are formed either by anabolism or catabolism (Ehrlich pathway) of amino acids. Esters are formed by enzymatic condensation of organic acids and alcohols. The current paper reviews the up-to-date knowledge in the pathways involving the synthesis of higher alcohols and esters by brewing yeasts. Fermentation parameters affecting yeast response during biosynthesis of these aromatic substances are also fully reviewed.Eduardo Pires gratefully acknowledges the Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) for the PhD fellowship support (SFRH/BD/61777/2009). The financial contributions of the EU FP7 project Ecoefficient Biodegradable Composite Advanced Packaging (EcoBioCAP, grant agreement no. 265669) as well as of the Grant Agency of the Czech Republic (project GACR P503/12/1424) are also gratefully acknowledged. The authors thank the Ministry of Education, Youth and Sports of the Czech Republic (MSM 6046137305) for their financial support

Treatment with Imatinib in NSCLC is associated with decrease of phosphorylated PDGFR-β and VEGF expression, decrease in interstitial fluid pressure and improvement of oxygenation

Elevated intratumoral interstitial fluid pressure (IFP) and tumour hypoxia are independent predictive factors for poor survival and poor treatment response in cancer patients. However, the relationship between IFP and tumour hypoxia has not yet been clearly established. Preclinical studies have shown that lowering IFP improves treatment response to cytotoxic therapy. Interstitial fluid pressure can be reduced by inhibition of phosphorylated platelet-derived growth factor receptor-β (p-PDGFR-β), a tyrosine kinase receptor frequently overexpressed in cancer stroma, and/or by inhibition of VEGF, a growth factor commonly overexpressed in tumours overexpressing p-PDGFR-β. We hypothesised that Imatinib, a specific PDGFR-β inhibitor will, in addition to p-PDGFR-β inhibition, downregulate VEGF, decrease IFP and improve tumour oxygenation. A549 human lung adenocarcinoma xenografts overexpressing PDGFR-β were grown in nude mice. Tumour-bearing animals were randomised to control and treatment groups (Imatinib 50 mg kg−1 via gavage for 4 days). Interstitial fluid pressure was measured in both groups before and after treatment. EF5, a hypoxia marker, was administered 3 h before being killed. Tumours were sectioned and stained for p-PDGFR-β, VEGF and EF5 binding. Stained sections were viewed with a fluorescence microscope and image analysis was performed. Imatinib treatment resulted in significant reduction of p-PDGFR-β, VEGF and IFP. Tumour oxygenation was also significantly improved. This study shows that p-PDGFR-β-overexpressing tumours can be effectively treated with Imatinib to decrease tumour IFP. Importantly, this is the first study demonstrating that Imatinib treatment improves tumour oxygenation and downregulates tumour VEGF expression

Complex Consequences of Herbivory and Interplant Cues in Three Annual Plants

Information exchange (or signaling) between plants following herbivore damage has recently been shown to affect plant responses to herbivory in relatively simple natural systems. In a large, manipulative field study using three annual plant species (Achyrachaena mollis, Lupinus nanus, and Sinapis arvensis), we tested whether experimental damage to a neighboring conspecific affected a plant's lifetime fitness and interactions with herbivores. By manipulating relatedness between plants, we assessed whether genetic relatedness of neighboring individuals influenced the outcome of having a damaged neighbor. Additionally, in laboratory feeding assays, we assessed whether damage to a neighboring plant specifically affected palatability to a generalist herbivore and, for S. arvensis, a specialist herbivore. Our study suggested a high level of contingency in the outcomes of plant signaling. For example, in the field, damaging a neighbor resulted in greater herbivory to A. mollis, but only when the damaged neighbor was a close relative. Similarly, in laboratory trials, the palatability of S. arvensis to a generalist herbivore increased after the plant was exposed to a damaged neighbor, while palatability to a specialist herbivore decreased. Across all species, damage to a neighbor resulted in decreased lifetime fitness, but only if neighbors were closely related. These results suggest that the outcomes of plant signaling within multi-species neighborhoods may be far more context-specific than has been previously shown. In particular, our study shows that herbivore interactions and signaling between plants are contingent on the genetic relationship between neighboring plants. Many factors affect the outcomes of plant signaling, and studies that clarify these factors will be necessary in order to assess the role of plant information exchange about herbivory in natural systems

A 10 year study of the cause of death in children under 15 years in Manhiça, Mozambique

<p>Abstract</p> <p>Background</p> <p>Approximately 46 million of the estimated 60 million deaths that occur in the world each year take place in developing countries. Further, this mortality is highest in Sub-Saharan Africa, although causes of mortality in this region are not well documented. The objective of this study is to describe the most frequent causes of mortality in children under 15 years of age in the demographic surveillance area of the Manhiça Health Research Centre, between 1997 and 2006, using the verbal autopsy tool.</p> <p>Methods</p> <p>Verbal autopsy interviews for causes of death in children began in 1997. Each questionnaire was reviewed independently by three physicians with experience in tropical paediatrics, who assigned the cause of death according to the International Classification of Diseases (ICD-10). Each medical doctor attributed a minimum of one and a maximum of 2 causes. A final diagnosis is reached when at least two physicians agreed on the cause of death.</p> <p>Results</p> <p>From January 1997 to December 2006, 568499 person-year at risk (pyrs) and 10037 deaths were recorded in the Manhiça DSS. 3730 deaths with 246658 pyrs were recorded for children under 15 years of age. Verbal autopsy interviews were conducted on 3002 (80.4%) of these deaths. 73.6% of deaths were attributed to communicable diseases, non-communicable diseases accounted for 9.5% of the defined causes of death, and injuries for 3.9% of causes of deaths. Malaria was the single largest cause, accounting for 21.8% of cases. Pneumonia with 9.8% was the second leading cause of death, followed by HIV/AIDS (8.3%) and diarrhoeal diseases with 8%.</p> <p>Conclusion</p> <p>The results of this study stand out the big challenges that lie ahead in the fight against infectious diseases in the study area. The pattern of childhood mortality in Manhiça area is typical of developing countries where malaria, pneumonia and HIV/AIDS are important causes of death.</p