Showing papers by "Nova Southeastern University published in 2015"

The Global Burden of Cancer 2013

Abstract: Importance Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. Objective To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. Evidence Review The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. Findings In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. Conclusions and Relevance Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.

Trends in Opioid Analgesic Abuse and Mortality in the United States

Abstract: Background The use of prescription opioid medications has increased greatly in the United States during the past two decades; in 2010, there were 16,651 opioid-related deaths. In response, hundreds of federal, state, and local interventions have been implemented. We describe trends in the diversion and abuse of prescription opioid analgesics using data through 2013. Methods We used five programs from the Researched Abuse, Diversion, and AddictionRelated Surveillance (RADARS) System to describe trends between 2002 and 2013 in the diversion and abuse of all products and formulations of six prescription opioid analgesics: oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol. The programs gather data from drug-diversion investigators, poison centers, substance-abuse treatment centers, and college students. Results Prescriptions for opioid analgesics increased substantially from 2002 through 2010 in the United States but then decreased slightly from 2011 through 2013. In general, RADARS System programs reported large increases in the rates of opioid diversion and abuse from 2002 to 2010, but then the rates flattened or decreased from 2011 through 2013. The rate of opioid-related deaths rose and fell in a similar pattern. Reported nonmedical use did not change significantly among college students.

Member Checking: Can Benefits Be Gained Similar to Group Therapy?

Abstract: Member checking continues to be an important quality control process in qualitative research as during the course of conducting a study, participants receive the opportunity to review their statements for accuracy and, in so doing; they may acquire a therapeutic benefit. The authors of this article suggest that this benefit is similar to some of the components of group therapy, especially in normalizing the phenomenon being experienced. Even if the participants never meet, they can feel a sense of relief that their feelings are validated and that they are not alone.

Correction: Corrigendum: Gap junctional protein Cx43 is involved in the communication between extracellular vesicles and mammalian cells

Abstract: Intercellular communication is vital to ensure tissue and organism homeostasis and can occur directly, between neighbour cells via gap junctions (GJ), or indirectly, at longer distances, through extracellular vesicles, including exosomes. Exosomes, as intercellular carriers of messenger molecules, mediate the transfer of biological information between donor and acceptor cells. Although the biological effects of exosomes in target cells have been intensively studied, the mechanisms that govern exosomal uptake are not fully understood. Here, we show that Connexin 43 (Cx43), the most widely expressed GJ protein, is present in exosomes in the form of hexameric channels and, more importantly, that exosomal Cx43 is able to modulate the interaction and transfer of information between exosomes and acceptor cells. This study envisions a new paradigm where Cx43-containing channels mediate the release of exosomal content into cells, which constitutes a novel and unanticipated mechanism to modulate intercellular communication.

Mental health outcomes in times of economic recession: a systematic literature review.

Abstract: Countries in recession experience high unemployment rates and a decline in living conditions, which, it has been suggested, negatively influences their populations’ health. The present review examines the recent evidence of the possible association between economic recessions and mental health outcomes. Literature review of records identified through Medline, PsycINFO, SciELO, and EBSCO Host. Only original research papers, published between 2004 and 2014, peer-reviewed, non-qualitative research, and reporting on associations between economic factors and proxies of mental health were considered. One-hundred-one papers met the inclusion criteria. The evidence was consistent that economic recessions and mediators such as unemployment, income decline, and unmanageable debts are significantly associated with poor mental wellbeing, increased rates of common mental disorders, substance-related disorders, and suicidal behaviours. On the basis of a thorough analysis of the selected investigations, we conclude that periods of economic recession are possibly associated with a higher prevalence of mental health problems, including common mental disorders, substance disorders, and ultimately suicidal behaviour. Most of the research is based on cross-sectional studies, which seriously limits causality inferences. Conclusions are summarised, taking into account international policy recommendations concerning the cost-effective measures that can possibly reduce the occurrence of negative mental health outcomes in populations during periods of economic recession.

Mixed-Methods Research Methodologies

Abstract: Mixed-Methods Studies Studies that are products of the pragmatist paradigm and that combine the qualitative and quantitative approaches within different phases of the research process. (Tashakkori & Teddlie, 2008, p.22). The Origins of Mixed-Methods Lie in the Two Major Research Paradigms * Quantitative research (i.e., a positivist paradigm) has historically been the cornerstone of social-science research. Purists call for researchers to "eliminate their biases, remain emotionally detached and uninvolved with the objects of study and test or empirically justify their stated hypotheses" (Johnson & Onwuegbuzie, 2004, p.14). * Qualitative purists support a constructivist or interpretivist paradigm and "contend that multiple-constructed realities abound, that time- and context-free generalizations are neither desirable nor possible, that research is value-bound, that it is impossible to differentiate fully causes and effects, that logic flows from specific to general and that knower and known cannot be separated because the subjective knower is the only source of reality" (Johnson & Onwuegbuzie, 2004, p. 14). The End of the "Paradigm Wars" and the Emergence of Mixed Methods * Calls in the 80's and 90's for "a truce" between the two major paradigms. * Many major authors and researchers felt that quantitative and qualitative research methodologies are compatible. * Paradigm relativism--"the use of whatever philosophical and/or methodological approach (that) works for the particular research problem under study" (Tashakkori & Teddlie, 2008, p. 9). * Many social-scientists now believe there is no major problem area that should be studied exclusively with one research method. * Quantitative tells us "If"; qualitative tells us "How or why". The Applications of Mixed-Methods Research are Far Ranging * Nursing * Psychology * Education * Sociology * Library and Information Science * Information Systems * Political Science The Type of Multi-Method Approach Depends Upon Four Factors * Theoretical perspective ** Explicit--based firmly on a theory ** Implicit--based indirectly on a theory * Priority of strategy ** Equal ** Qualitative ** Quantitative * Sequence of data collection implementation ** Qualitative first ** Quantitative first ** No sequence * The point at which the data are integrated ** At data collection ** At data analysis ** At data interpretation ** With some combination Sequential Explanatory Strategy [ILLUSTRATION OMITTED] * The collection and analysis of quantitative data followed by the collection and analysis of qualitative data. * Equal priority is given to the two phases. * Data are integrated during interpretation. * Primary focus is to explain quantitative results by exploring certain results in more detail or helping explain unexpected results (e.g., using follow-up interviews to better understand the results of a quantitative study). * Strengths: relatively straight forward due to clear, distinct stages and easier to describe than concurrent strategies. * Weakness: very time consuming especially when both phases are given equal consideration and priority. [ILLUSTRATION OMITTED] * The collection and analysis of qualitative data followed by the collection and analysis of quantitative data. * Equal priority is given to the two phases but priority can be given to either. * Data are integrated during interpretation. * Used primarily to explore a phenomenon by: ** Testing elements of a theory ** Generalizing qualitative findings to different samples ** Development of instrumentation (e. …

SmileFinder: A Resampling-Based Approach to Evaluate Signatures of Selection from Genome-Wide Sets of Matching Allele Frequency Data in Two or More Diploid Populations

Abstract: Background Adaptive alleles may rise in frequency as a consequence of positive selection, creating a pattern of decreased variation in the neighboring loci, known as a selective sweep. When the region containing this pattern is compared to another population with no history of selection, a rise in variance of allele frequencies between populations is observed. One challenge presented by large genome-wide datasets is the ability to differentiate between patterns that are remnants of natural selection from those expected to arise at random and/or as a consequence of selectively neutral demographic forces acting in the population.

Number of people blind or visually impaired by cataract worldwide and in world regions, 1990 to 2010

Abstract: Purpose: To estimate prevalence and number of people visually impaired or blind due to cataract. Methods: Based on the Global Burden of Diseases Study 2010 and ongoing literature research, we examined how many people were affected by moderate to severe vision impairment (MSVI; presenting visual acuity <6/18, ≥3/60) and blindness (presenting visual acuity <3/60) due to cataract. Results: In 2010, of overall 32.4 million blind and 191 million vision impaired, 10.8 million people were blind and 35.1 million were visually impaired due to cataract. Cataract caused worldwide 33.4% of all blindness in 2010, and 18.4% of all MSVI. These figures were lower in the high-income regions ( 40%) in South and Southeast Asia and Oceania. From 1990 to 2010, the number of blind or visually impaired due to cataract decreased by 11.4% and by 20.2%, respectively; the age-standardized global prevalence of cataract-related blindness and MSVI reduced by 46% and 50%, respectively, and the worldwide crude prevalence of cataract-related blindness and MSVI reduced by 32% and 39%, respectively. The percentage of global blindness and MSVI caused by cataract decreased from 38.6% to 33.4%, and from 25.6% to 18.4%, respectively. This decrease took place in almost all world regions, except East Sub-Saharan Africa. Conclusions: In 2010, one in three blind people was blind due to cataract, and one of six visually impaired people was visually impaired due to cataract. Despite major improvements in terms of reduction of prevalence, cataract remains a major public health problem.

Phase 3 Trial of Flutemetamol Labeled With Radioactive Fluorine 18 Imaging and Neuritic Plaque Density

Abstract: Importance In vivo imaging of brain β-amyloid, a hallmark of Alzheimer disease, may assist in the clinical assessment of suspected Alzheimer disease. Objective To determine the sensitivity and specificity of positron emission tomography imaging with flutemetamol injection labeled with radioactive fluorine 18 to detect β-amyloid in the brain using neuropathologically determined neuritic plaque levels as the standard of truth. Design, Setting, and Participants Open-label multicenter imaging study that took place at dementia clinics, memory centers, and hospice centers in the United States and England from June 22, 2010, to November 23, 2011. Participants included terminally ill patients who were 55 years or older with a life expectancy of less than 1 year. Interventions Flutemetamol injection labeled with radioactive fluorine 18 (Vizamyl; GE Healthcare) administration followed by positron emission tomography imaging and subsequent brain donation. Main Outcomes and Measures Sensitivity and specificity of flutemetamol injection labeled with radioactive fluorine 18 positron emission tomography imaging for brain β-amyloid. Images were reviewed without and with computed tomography scans and classified as positive or negative for β-amyloid by 5 readers who were blind to patient information. In patients who died, neuropathologically determined neuritic plaque levels were used to confirm scan interpretations and determine sensitivity and specificity. Results Of 176 patients with evaluable images, 68 patients (38%) died during the study, were autopsied, and had neuritic plaque levels determined; 25 brains (37%) were β-amyloid negative; and 43 brains (63%) were β-amyloid positive. Imaging was performed a mean of 3.5 months (range, 0 to 13 months) before death. Sensitivity without computed tomography was 81% to 93% (median, 88%). Median specificity was 88%, with 4 of 5 of the readers having specificity greater than 80%. When scans were interpreted with computed tomography images, sensitivity and specificity improved for most readers but the differences were not significant. The area under the receiver operating curve was 0.90. There were no clinically meaningful findings in safety parameters. Conclusions and Relevance This study showed that flutemetamol injection labeled with radioactive fluorine 18 was safe and had high sensitivity and specificity in an end-of-life population. In vivo detection of brain β-amyloid plaque density may increase diagnostic accuracy in cognitively impaired patients.

The effects of self-myofascial release using a foam roll or roller massager on joint range of motion, muscle recovery, and performance: a systematic review.

Abstract: Background Self‐myofascial release (SMR) is a popular intervention used to enhance a client's myofascial mobility. Common tools include the foam roll and roller massager. Often these tools are used as part of a comprehensive program and are often recommended to the client to purchase and use at home. Currently, there are no systematic reviews that have appraised the effects of these tools on joint range of motion, muscle recovery, and performance.

Measurements of Higgs boson production and couplings in the four-lepton channel in pp collisions at center-of-mass energies of 7 and 8 TeV with the ATLAS detector

Abstract: The final ATLAS Run 1 measurements of Higgs boson production and couplings in the decay channel H -> ZZ* -> l(+)l(-)l(+)l'(-), where l, l' = e or mu, are presented. These measurements were performed using pp collision data corresponding to integrated luminosities of 4.5 and 20.3 fb(-1) at center-of-mass energies of 7 and 8 TeV, respectively, recorded with the ATLAS detector at the LHC. The H -> ZZ* -> 4l signal is observed with a significance of 8.1 standard deviations, with an expectation of 6.2 standard deviations, at m(H) = 125.36 GeV, the combined ATLAS measurement of the Higgs boson mass from the H -> gamma gamma and H -> ZZ* -> 4l channels. The production rate relative to the Standard Model expectation, the signal strength, is measured in four different production categories in the H -> ZZ* -> 4l channel. The measured signal strength, at this mass, and with all categories combined, is 1.44(-0.33)(+0.40). The signal strength for Higgs boson production in gluon fusion or in association with (tt) over bar or (bb) over bar pairs is found to be 1.7(-0.4)(+0.5), while the signal strength for vector-boson fusion combined with WH/ZH associated production is found to be 0.3(-0.9)(+1.6).

Operationalizing resilience for adaptive coral reef management under global environmental change.

Abstract: Cumulative pressures from global climate and ocean change combined with multiple regional and local-scale stressors pose fundamental challenges to coral reef managers worldwide. Understanding how cumulative stressors affect coral reef vulnerability is critical for successful reef conservation now and in the future. In this review, we present the case that strategically managing for increased ecological resilience (capacity for stress resistance and recovery) can reduce coral reef vulnerability (risk of net decline) up to a point. Specifically, we propose an operational framework for identifying effective management levers to enhance resilience and support management decisions that reduce reef vulnerability. Building on a system understanding of biological and ecological processes that drive resilience of coral reefs in different environmental and socio-economic settings, we present an Adaptive Resilience-Based management (ARBM) framework and suggest a set of guidelines for how and where resilience can be enhanced via management interventions. We argue that press-type stressors (pollution, sedimentation, overfishing, ocean warming and acidification) are key threats to coral reef resilience by affecting processes underpinning resistance and recovery, while pulse-type (acute) stressors (e.g. storms, bleaching events, crown-of-thorns starfish outbreaks) increase the demand for resilience. We apply the framework to a set of example problems for Caribbean and Indo-Pacific reefs. A combined strategy of active risk reduction and resilience support is needed, informed by key management objectives, knowledge of reef ecosystem processes and consideration of environmental and social drivers. As climate change and ocean acidification erode the resilience and increase the vulnerability of coral reefs globally, successful adaptive management of coral reefs will become increasingly difficult. Given limited resources, on-the-ground solutions are likely to focus increasingly on actions that support resilience at finer spatial scales, and that are tightly linked to ecosystem goods and services.

Searches for Higgs boson pair production in the hh →bbττ, γγWW∗, γγbb, bbbb channels with the ATLAS detector

Abstract: Searches for both resonant and nonresonant Higgs boson pair production are performed in the hh -> bb tau tau, gamma gamma WW* final states using 20.3 fb(-1) of pp collision data at a center-of-m ...

International society of sports nutrition position stand: Beta-Alanine.

Abstract: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of beta-alanine supplementation. Based on the current available literature, the conclusions of the ISSN are as follows: 1) Four weeks of beta-alanine supplementation (4–6 g daily) significantly augments muscle carnosine concentrations, thereby acting as an intracellular pH buffer; 2) Beta-alanine supplementation currently appears to be safe in healthy populations at recommended doses; 3) The only reported side effect is paraesthesia (tingling), but studies indicate this can be attenuated by using divided lower doses (1.6 g) or using a sustained-release formula; 4) Daily supplementation with 4 to 6 g of beta-alanine for at least 2 to 4 weeks has been shown to improve exercise performance, with more pronounced effects in open end-point tasks/time trials lasting 1 to 4 min in duration; 5) Beta-alanine attenuates neuromuscular fatigue, particularly in older subjects, and preliminary evidence indicates that beta-alanine may improve tactical performance; 6) Combining beta-alanine with other single or multi-ingredient supplements may be advantageous when supplementation of beta-alanine is high enough (4–6 g daily) and long enough (minimum 4 weeks); 7) More research is needed to determine the effects of beta-alanine on strength, endurance performance beyond 25 min in duration, and other health-related benefits associated with carnosine.

Natural Killer Cell-Based Therapies Targeting Cancer: Possible Strategies to Gain and Sustain Anti-Tumor Activity.

Abstract: Natural killer (NK) cells were discovered 40 years ago, by their ability to recognize and kill tumor cells without the requirement of prior antigen exposure. Since then NK cells have been seen as promising agents for cell-based cancer therapies. However, NK cells represent only a minor fraction of the human lymphocyte population. Their skewed phenotype and impaired functionality during cancer progression necessitates the development of clinical protocols to activate and expand to high numbers ex vivo to be able to infuse sufficient numbers of functional NK cells to the cancer patients. Initial NK cell-based clinical trials suggested that NK cell-infusion is safe and feasible with almost no NK cell-related toxicity, including graft-versus-host disease (GvHD). Complete remission and increased disease free survival is shown in a small number of patients with hematological malignances. Furthermore, successful adoptive NK cell based therapies from haploidentical donors have been demonstrated. Disappointingly, only limited anti-tumor effects have been demonstrated following NK cell infusion in patients with solid tumors. While NK cells have great potential in targeting tumor cells, the efficiency of NK cell functions in the tumor microenvironment is yet unclear. The failure of immune surveillance may in part be due to sustained immunological pressure on tumor cells resulting in the development of tumor escape variants that are invisible to the immune system. Alternatively, this could be due to the complex network of immune suppressive compartments in the tumor microenvironment, including myeloid-derived suppressor cells, tumor associated macrophages, and regulatory T cells. Although the negative effect of the tumor microenvironment on NK cells can be transiently reverted by ex vivo-expansion and long-term activation, the abovementioned NK cell/tumor microenvironment interactions upon reinfusion are not fully elucidated. Within this context, genetic modification of NK cells may provide new possibilities for developing effective cancer immunotherapies by improving NK cell responses and making them less susceptible to the tumor microenvironment. Within this review we will discuss clinical trials using NK cells with a specific reflection on novel potential strategies, such as genetic modification of NK cells and complementary therapies aimed at improving the clinical outcome of NK cell-based immune therapies.

Using Social Media and Targeted Snowball Sampling to Survey a Hard-to-reach Population: A Case Study

Abstract: Response rates to the academic surveys used in quantitative research are decreasing and have been for several decades among both individuals and organizations. Given this trend, providing doctoral students an opportunity to complete their dissertations in a timely and cost effective manner may necessitate identifying more innovative and relevant ways to collect data while maintaining appropriate research standards and rigor. The case of a research study is presented which describes the data collection process used to survey a hard-to-reach population. It details the use of social media, in this case LinkedIn, to facilitate the distribution of the web-based survey. A roadmap to illustrate how this data collection process unfolded is presented, as well as several “lessons learned” during this journey. An explanation of the considerations that impacted the sampling design is provided. The goal of this case study is to provide researchers, including doctoral students, with realistic expectations and an awareness of the benefits and risks associated with the use of this method of data collection.

Search for high-mass diphoton resonances in pp collisions at √s = 8 TeV with the ATLAS detector

Abstract: Search for high-mass diphoton resonances in pp collisions at pffisffi root s=8 TeV with the ATLAS detector

Pathophysiology of Sepsis-Related Cardiac Dysfunction: Driven by Inflammation, Energy Mismanagement, or Both?

Abstract: Sepsis is a systemic inflammatory response that follows bacterial infection. Cardiac dysfunction is an important consequence of sepsis that affects mortality and has been attributed to either elevated inflammation or suppression of both fatty acid and glucose oxidation and eventual ATP depletion. Moreover, cardiac adrenergic signaling is compromised in septic patients and this aggravates further heart function. While anti-inflammatory therapies are important for the treatment of the disease, administration of anti-inflammatory drugs did not improve survival in septic patients. This review article summarizes findings on inflammatory and other mechanisms that are triggered in sepsis and affect cardiac function and mortality. Particularly, it focuses on the effects of the disease in metabolic pathways, as well as in adrenergic signaling and the potential interplay of the latter with inflammation. It is suggested that therapeutic approaches should include combination of anti-inflammatory treatments, stimulation of energy production, and restoration of adrenergic signaling in the heart.

Genomic legacy of the African cheetah, Acinonyx jubatus.

Abstract: Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084–12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p 80 %) pleiomorphic sperm. The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species’ natural history, physiological adaptations and unique reproductive disposition.

MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation

Abstract: Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.

Phenotypes and endotypes of rhinitis and their impact on management: a PRACTALL report.

Abstract: Rhinitis is an umbrella term that encompasses many different subtypes, several of which still elude complete characterization. The concept of phenotyping, being the definition of disease subtypes on the basis of clinical presentation, has been well established in the last decade. Classification of rhinitis entities on the basis of phenotypes has facilitated their characterization and has helped practicing clinicians to efficiently approach rhinitis patients. Recently, the concept of endotypes, that is, the definition of disease subtypes on the basis of underlying pathophysiology, has emerged. Phenotypes/endotypes are dynamic, overlapping, and may evolve into one another, thus rendering clear-cut definitions difficult. Nevertheless, a phenotype-/endotype-based classification approach could lead toward the application of stratified and personalized medicine in the rhinitis field. In this PRACTALL document, rhinitis phenotypes and endotypes are described, and rhinitis diagnosis and management approaches focusing on those phenotypes/endotypes are presented and discussed. We emphasize the concept of control-based management, which transcends all rhinitis subtypes.

Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).

Abstract: Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

Improvement of mineral and bone metabolism markers is associated with better survival in haemodialysis patients: the COSMOS study

Abstract: Background: Abnormalities in serum phosphorus, calcium and parathyroid hormone (PTH) have been associated with poor survival in haemodialysis patients. This COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) analysis assesses the association of high and low serum phosphorus, calcium and PTH with a relative risk of mortality. Furthermore, the impact of changes in these parameters on the relative risk of mortality throughout the 3-year follow-up has been investigated. Methods: COSMOS is a 3-year, multicentre, open-cohort, prospective study carried out in 6797 adult chronic haemodialysis patients randomly selected from 20 European countries. Results: Using Cox proportional hazard regression models and penalized splines analysis, it was found that both high and low serum phosphorus, calcium and PTH were associated with a higher risk of mortality. The serum values associated with the minimum relative risk of mortality were 4.4 mg/dL for serum phosphorus, 8.8 mg/dL for serum calcium and 398 pg/mL for serum PTH. The lowest mortality risk ranges obtained using as base the previous values were 3.6-5.2 mg/dL for serum phosphorus, 7.9-9.5 mg/dL for serum calcium and 168-674 pg/mL for serum PTH. Decreases in serum phosphorus and calcium and increases in serum PTH in patients with baseline values of >5.2 mg/dL (phosphorus), >9.5 mg/dL (calcium) and <168 pg/mL (PTH), respectively, were associated with improved survival. Conclusions: COSMOS provides evidence of the association of serum phosphorus, calcium and PTH and mortality, and suggests survival benefits of controlling chronic kidney disease-mineral and bone disorder biochemical parameters in CKD5D patients.

Gap geometry dictates epithelial closure efficiency

Abstract: Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity.