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Objetivo. Identificar las creencias y conocimientos de un grupo de médicos rurales sobre el manejo de alimentación en los casos de diarrea aguda de los menores de cinco años y compararlos con la recomendación de la Organización Mundial de la Salud (OMS). Material y métodos. Se realizó un estudio de antropología cognitiva con los 10 médicos que brindan atención a la población infantil en el Hospital Rural del IMSS-Solidaridad de San Juanito, Bocoyna, Chihuahua, México, de julio a diciembre de 1998. Se trianguló la información obtenida por las técnicas de grupos focales, viñetas, listado libre, sorteo de montones y cuestionario semiestructurado. Resultados. Los médicos reconocieron el impacto negativo de la diarrea sobre el estado nutricio del niño, pero no todos evaluaron su estado de nutrición. Como tratamientos predominaron los antimicrobianos, el manejo con líquidos y las recomendaciones sobre alimentación. De éstas, las más consistentes fueron la lactancia materna, la alimentación tardía y la dieta "escalonada". Conclusiones. La información obtenida contrasta con la recomendación de la OMS, en especial con la de alimentación sostenida.

Abstract Background In Mexico, as in other developing countries, micronutrient deficiencies are common in infants between 6 and 24 months of age and are an important public health problem. The objective of this study was to determine the prevalence of anemia and of iron, folic acid, and zinc deficiencies in Mexican children under 2 years of age who use the health care services provided by the Mexican Institute for Social Security (IMSS). Methods A nationwide survey was conducted with a representative sample of children younger than 2 years of age, beneficiaries, and users of health care services provided by IMSS through its regular regimen (located in urban populations) and its Oportunidades program (services offered in rural areas). A subsample of 4,955 clinically healthy children was studied to determine their micronutrient status. A venous blood sample was drawn to determine hemoglobin, serum ferritin, percent of transferrin saturation, zinc, and folic acid. Descriptive statistics include point estimates and 95% confidence intervals for the sample and projections for the larger population from which the sample was drawn. Results Twenty percent of children younger than 2 years of age had anemia, and 27.8% (rural) to 32.6% (urban) had iron deficiency; more than 50% of anemia was not associated with low ferritin concentrations. Iron stores were more depleted as age increased. Low serum zinc and folic acid deficiencies were 28% and 10%, respectively, in the urban areas, and 13% and 8%, respectively, in rural areas. The prevalence of simultaneous iron and zinc deficiencies was 9.2% and 2.7% in urban and rural areas. Children with anemia have higher percentages of folic acid deficiency than children with normal iron status. Conclusion Iron and zinc deficiencies constitute the principal micronutrient deficiencies in Mexican children younger than 2 years old who use the health care services provided by IMSS. Anemia not associated with low ferritin values was more prevalent than iron-deficiency anemia. The presence of micronutrient deficiencies at this early age calls for effective preventive public nutrition programs to address them.

A Cyber-Physical-Social System (CPSS) is an evolving subset of Cyber-Physical Systems (CPS), which involve the interlinking of the cyber, physical, and social domains within a system-of-systems mindset. CPSS is in a growing state, which combines secure digital technologies with physical systems (e.g., sensors and actuators) and incorporates social aspects (e.g., human interactions and behaviors, and societal norms) to facilitate automated and secure services to end-users and organisations. This paper reviews the field of CPSS, especially in the scope of complexity theory and cyber security to determine its impact on CPS and social media's influence activities. The significance of CPSS lies in its potential to provide solutions to complex societal problems that are difficult to address through traditional approaches. With the integration of physical, social, and cyber components, CPSS can realize the full potential of IoT, big data analytics, and machine learning, leading to increased efficiency, improved sustainability and better decision making. CPSS presents exciting opportunities for innovation and advancement in multiple domains, improving the quality of life for people around the world. Research challenges to CPSS include the integration of hard and soft system components within all three domains, in addition to sociological metrics, data security, processing optimization and ethical implications. The findings of this paper note key research trends in the fields of CPSS, and recent novel contributions, followed by identified research gaps and future work.

Poor quality jobs, incorporating job demands, resources and rewards, can impact employees' health and wellbeing inside and outside work. However, jobs' changing nature and employees' increasingly diverse backgrounds mean existing job quality models may not adequately explain individuals' job quality experiences within their individual, organisational and societal contexts. The paper aimed to understand mothers, fathers and childless women and men's gendered, classed and aged experiences of quantitative job demands (including work amount, speed, effort, length and timing) and their resources and rewards, within multilevel contexts. We conducted a qualitative case-study of an Australian organisation, employing a critical feminist grounded theory design. We collected and analysed data from open-ended questionnaire responses from 47 employees and iterative in-depth interviews with 10 employees. Participants' experiences of excessive quantitative demands, whether they could meet such demands, and whether they felt extrinsically or intrinsically resourced and rewarded for doing so, were embedded within ComCo's masculine-neoliberal-capitalist growth imperative, cultures, policies and practices reinforcing growth, and quantitatively extreme and qualitatively conformant ideal worker discourses, as well as participants' organisationally and societally-embedded individual, family and community-level contexts; producing nuanced gendered, classed and aged experiences among mothers, fathers and childless women and men. Although confirming well-established objective job quality dimensions, our research suggests individuals' nuanced and subjective job quality experiences are embedded within individual, family, community, organisational and societal contexts., Competing Interests: Competing InterestsThe authors have no relevant financial or non-financial interests to declare., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The 4-valent human papillomavirus (HPV) vaccine (4vHPV vaccine), Gardasil®, is indicated for the prevention of several HPV-related diseases. The objective was to assess the safety of 4vHPV vaccine administered to males as part of routine care. The study used a US health insurance claims database, and included males, age 9 to 26 years, who initiated 4vHPV between October 2009 and December 2016. General safety outcomes were identified using ICD diagnosis codes associated with emergency room visits and hospitalizations in the claims database in risk periods (Days 1-60 and Days 1-14 following vaccine administration) and self-comparison periods (Days 91-150 and 91-104 for the Days 1-60 and Days 1-14 analysis, respectively). Incidence rates (IRs) and relative rates (RRs) with 95% confidence intervals (CIs) were calculated comparing the risk and self-comparison periods. In this study, 114,035 males initiated 4vHPV vaccine and received 202,737 doses. Using the 60-day time window, 5 outcomes had significantly elevated RRs after accounting for multiple comparisons: ear conditions (RR 1.28, 95% CI 1.03-1.59); otitis media and related conditions (RR 1.65, 95% CI 1.09-2.54); cellulitis and abscess of arm (RR 2.17, 95% CI 1.06-4.72); intracranial injury (RR 1.23, 95% CI 1.01-1.50); and concussion (RR 1.29, 95% CI 1.05-1.59). A higher rate of allergic reactions was noted on the day of 4vHPV vaccine receipt compared to other vaccines (21.07 events per 10,000 doses, 95% CI 18.89-23.44 versus 11.44 per 10,000 doses, 95% CI 9.84-13.22). A higher incidence rate of VTE was observed following vaccination but this association was not significant (RR 2.17, 95% CI 0.35-22.74). The 4vHPV vaccine was associated with same-day allergic reactions as well as ear infections, intracranial injury, cellulitis, and concussion within 2 months after vaccination. While allergic reaction and cellulitis are consistent with the known safety profile of 4vHPV vaccine, the association of the other outcomes were determined by an independent Safety Review Committee to be most likely a result of activities common in adolescent males that coincide with the timing of vaccination and not directly related to vaccination itself. Implications and Contributions : The study results support the general safety of routine immunization with 4vHPV vaccine among males to prevent HPV-related diseases and cancers.

Microglia, the brain's resident macrophages, shape neural development and are key neuroimmune hubs in the pathological signatures of neurodevelopmental disorders. Despite the importance of microglia, their development has not been carefully examined in the human brain, and most of our knowledge derives from rodents. We aimed to address this gap in knowledge by establishing an extensive collection of 97 post-mortem tissues in order to enable quantitative, sex-matched, detailed analysis of microglia across the human lifespan. We identify the dynamics of these cells in the human telencephalon, describing waves in microglial density across gestation, infancy, and childhood, controlled by a balance of proliferation and apoptosis, which track key neurodevelopmental milestones. These profound changes in microglia are also observed in bulk RNA-seq and single-cell RNA-seq datasets. This study provides a detailed insight into the spatiotemporal dynamics of microglia across the human lifespan and serves as a foundation for elucidating how microglia contribute to shaping neurodevelopment in humans., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Santa Fe Gully zone is a marginalized area of Mexico City where nearly 39% of children live with either overweight or obesity. Despite the extensive research on obesogenic behaviors, studies frequently overlook the contexts where such behaviors occur. This qualitative study described individual and familial obesogenic behaviors among children with obesity from Santa Fe Gully, and explained how these behaviors might be contextually shaped. We used a grounded theory approach to investigate the process of development/maintenance of obesity in our sample. Fifteen participants (seven 10-year-olds with overweight or obesity and their parents) participated in nine art-based focus groups, and parents completed individual semi-structured interviews. Data were analyzed using a structured thematic content analysis. Results showed children's weight status was part of their identity, providing children with a familial 'fitting' sense while increasing psychosocial difficulties, leading to emotional overeating as a coping strategy. Parents' use of controlling and low-structured parenting practices reinforced children's emotional overeating and failed to regulate children's dietary and physical activity behaviors. Some low-structured parenting practices were guilt-motivated or fostered by socioeconomic and cultural factors (e.g., limited food access, unhealthy food exposure, community unsafety). Future interventions in Santa Fe Gully aimed at modifying obesogenic behaviors should incorporate systemic and ecological approaches to help participants navigate through contextual obstacles, as their behaviors should be analized considering the context where they occur., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The quadrivalent human papillomavirus vaccine (4vHPV, GARDASIL® ) , was approved in the US in 2009 for use in males aged 9 to 26 for the prevention of HPV-related genital warts, and in 2010 for the prevention of certain HPV-related anogenital diseases. A regimen was approved in 2016 for those who initiate the vaccine series between the ages of 9 to 14 years. We describe patterns of 4vHPV administration among US males before this modification., Methods: The study used a US health insurance claims database, and included males, age 9 to 26 years, who initiated 4vHPV between 2012 and 2016. Time from first dose to subsequent doses was estimated. Logistic regression identified factors associated with regimen completion., Results: Among 100,786 males who initiated 4vHPV (corresponding to ∼ 13% of male birth cohorts), 50,573 (50.2%) and 25,763 (25.6%) received a second and third dose, respectively. Annual administration was common, with 47% of males receiving 3 doses over 3 years (1 dose per year) as compared to 12% receiving the 3-dose series in the recommended 6-month timeframe. Receipt of 4vHPV was 2.2 (range 1.5 to 2.9) times as likely to occur in summer months compared to other times of the year. Individuals aged 18 to 21 years and those living in Western states or rural regions were less likely to complete the 3-dose regimen., Conclusions: The real-world patterns of 4vHPV vaccination observed, particularly the low uptake and regimen completion, suggest that better strategies are needed for males to improve 4vHPV vaccine use in males., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The aim of this study was to identify serum ferritin (SF) cut-off points (COPs) in a cohort of healthy full-term normal birth weight infants who had repeated measurements of SF and haemoglobin every 3 months during the first year of life. The study included 746 full-term infants with birth weight ≥2,500 g, having uncomplicated gestations and births. Participants received prophylactic iron supplementation (1 mg/day of iron element) from the first to the 12th month of life and did not develop anaemia during the first year of life. Two statistical methods were considered to identify COPs for low iron stores at 3, 6, 9 and 12 months of age: deviation from mean and cluster analysis. According to the K-means cluster analysis results by age and sex, COPs at 3 and 6 months for girls were 39 and 21 μg/L and for boys 23 and 11 μg/L, respectively. A single COP of 10 μg/L was identified, for girls and boys, at both 9 and 12 months. Given the physiological changes in SF concentration during the first year of life, our study identified dynamic COPs, which differed by sex in the first semester. Adequate SF COPs are necessary to identify low iron stores at an early stage of iron deficiency, which represents one of the most widespread public health problems around the world, particularly in low- and middle-income countries., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Mexico has the highest prevalence globally for children who are overweight. We conducted a qualitative study to understand childhood obesity in Mexico and the complex factors at play. Data were collected at three elementary schools in a low socio-economic area in Mexico City. Semi-structured interviews were conducted with 60 children, 24 parents and 28 teachers. The children interviewed were between the ages of 8 and 12 years old. Interview texts were analysed using NVivo 9 and 10 and thematic discourse analysis was used. Findings revealed how children's choices around nutrition and physical activity were constrained by their environment and discursive constructions., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Duvelisib (also known as IPI-145) is an oral, dual inhibitor of phosphatidylinositol 3-kinase δ and γ (PI3K-δ,γ) being developed for treatment of hematologic malignancies. PI3K-δ,γ signaling can promote B-cell proliferation and survival in clonal B-cell malignancies, such as chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). In a phase 1 study, duvelisib showed clinically meaningful activity and acceptable safety in CLL/SLL patients. We report here the results of DUO, a global phase 3 randomized study of duvelisib vs ofatumumab monotherapy for patients with relapsed or refractory (RR) CLL/SLL. Patients were randomized 1:1 to oral duvelisib 25 mg twice daily (n = 160) or ofatumumab IV (n = 159). The study met the primary study end point by significantly improving progression-free survival per independent review committee assessment compared with ofatumumab for all patients (median, 13.3 months vs 9.9 months; hazard ratio [HR] = 0.52; P < .0001), including those with high-risk chromosome 17p13.1 deletions [del(17p)] and/or TP53 mutations (HR = 0.40; P = .0002). The overall response rate was significantly higher with duvelisib (74% vs 45%; P < .0001) regardless of del(17p) status. The most common adverse events were diarrhea, neutropenia, pyrexia, nausea, anemia, and cough on the duvelisib arm, and neutropenia and infusion reactions on the ofatumumab arm. The DUO trial data support duvelisib as a potentially effective treatment option for patients with RR CLL/SLL. This trial was registered at www.clinicaltrials.gov as #NCT02004522., (© 2018 by The American Society of Hematology.)

Objectives: This study sought to examine predictors of psychological well-being (PWB) among nursing students at an Australian regional university. The study postulated that: stress would have a negative effect on PWB; internal factors such as self-efficacy, resilience and mindfulness would have a positive effect on PWB and, external factors like social support would have a positive effect on PWB., Design: A cross sectional descriptive predictive model was used to test the study hypotheses., Setting and Participants: Convenience sampling was used to recruit participants at an Australian regional university with non-traditional nursing cohorts and where the curriculum is predominantly taught on-line., Methods: Six validated scales (The Perceived Stress Scale; General Self-Efficacy Scale; Connor Davidson Resilience Scale; Multi-Dimensional Scale of Perceived Social Support; Psychological Wellbeing Scale, Mindfulness Awareness Scale) and a demographic inventory were administered as an online survey. A multiple linear regression analysis was performed to assess the internal and external factors to predict the participants' PWB., Results: Of the 1760 invitations distributed, 657 responses were returned; however, because some were found to be significantly incomplete, 538 responses only were used for the data analysis. Demographics illustrated the characteristics of a non-traditional cohort that was female dominated. All three hypotheses were supported. An unexpected finding was that while it might be anticipated that non-traditional cohorts will have stronger coping skills due to life experiences, this should not be assumed. We found that our participants had higher stress scores and lower psychological wellbeing, compared to the younger groups (nursing or health allied) reported in previous studies. It was perhaps due to their difficulties in juggling responsibilities between study, work and family and the nature of studying externally online., Conclusions: This study represents only a snapshot in time but emphasises the need for specific curriculum preparation to promote positive coping strategies. In this way, new graduates may be better prepared to engage with complex, demanding and ever-changing work environments across the globe., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A super-hydrophobic surface has been obtained from nanocomposite materials based on silica nanoparticles and self-assembled monolayers of 1 H ,1 H ,2 H ,2 H -perfluorooctyltriethoxysilane (POTS) using spin coating and chemical vapor deposition methods. Scanning electron microscope images reveal the porous structure of the silica nanoparticles, which can trap small-scale air pockets. An average water contact angle of 163° and bouncing off of incoming water droplets suggest that a super-hydrophobic surface has been obtained based on the silica nanoparticles and POTS coating. The monitored water droplet icing test results show that icing is significantly delayed by silica-based nano-coatings compared with bare substrates and commercial icephobic products. Ice adhesion test results show that the ice adhesion strength is reduced remarkably by silica-based nano-coatings. The bouncing phenomenon of water droplets, the icing delay performance and the lower ice adhesion strength suggest that the super-hydrophobic coatings based on a combination of silica and POTS also show icephobicity. An erosion test rig based on pressurized pneumatic water impinging impact was used to evaluate the durability of the super-hydrophobic/icephobic coatings. The results show that durable coatings have been obtained, although improvement will be needed in future work aiming for applications in aerospace.

Objectives: Qutenza is a high-dose capsaicin patch used to relieve neuropathic pain from postherpetic neuralgia (PHN) and HIV-associated neuropathy (HIV-AN). In clinical studies, some patients had a dramatic response to the capsaicin patch. Our objective was to determine the baseline characteristics of patients who best benefit from capsaicin patch treatment., Methods: We conducted a meta-analysis of 6 completed randomized and controlled Qutenza studies by pooling individual patient data. Sustained response was defined as>50% decrease in the mean pain intensity from baseline to weeks 2 to 12, and Complete Response as an average pain intensity score≤1 during weeks 2 to 12. Logistic regression was used to identify predictors of response and Complete Response, and subgroups of patients who respond best to the capsaicin patch., Results: Baseline pain intensity score (BPIS)≤4 was a predictor of Sustained and Complete Response in PHN and HIV-AN patients; absence of allodynia and presence of hypoesthesia, and a McGill Pain Questionnaire (MPQ) sensory score <22 were predictors of Sustained Response in PHN patients; female sex was a predictor of Sustained and Complete Response in HIV-AN patients. Thus, characteristics associated with the highest chance of responding to the capsaicin patch were, for PHN, BPIS≤4, MPQ sensory score≤22, absence of allodynia, and presence of hypoesthesia; for HIV-AN, they were female sex and BPIS≤4. Patients with these characteristics had a statistically significantly greater chance of responding to the capsaicin patch than other patients., Discussion: We identified subpopulations of PHN and HIV-AN patients likely to benefit from the capsaicin patch.

Bortezomib frequently produces severe treatment-related peripheral neuropathy (PN) in Waldenström's macroglobulinemia (WM). Carfilzomib is a neuropathy-sparing proteasome inhibitor. We examined carfilzomib, rituximab, and dexamethasone (CaRD) in symptomatic WM patients naïve to bortezomib and rituximab. Protocol therapy consisted of intravenous carfilzomib, 20 mg/m2 (cycle 1) and 36 mg/m(2) (cycles 2-6), with intravenous dexamethasone, 20 mg, on days 1, 2, 8, and 9, and rituximab, 375 mg/m(2), on days 2 and 9 every 21 days. Maintenance therapy followed 8 weeks later with intravenous carfilzomib, 36 mg/m(2), and intravenous dexamethasone, 20 mg, on days 1 and 2, and rituximab, 375 mg/m(2), on day 2 every 8 weeks for 8 cycles. Overall response rate was 87.1% (1 complete response, 10 very good partial responses, 10 partial responses, and 6 minimal responses) and was not impacted by MYD88(L265P) or CXCR4(WHIM) mutation status. With a median follow-up of 15.4 months, 20 patients remain progression free. Grade ≥2 toxicities included asymptomatic hyperlipasemia (41.9%), reversible neutropenia (12.9%), and cardiomyopathy in 1 patient (3.2%) with multiple risk factors, and PN in 1 patient (3.2%) which was grade 2. Declines in serum IgA and IgG were common. CaRD offers a neuropathy-sparing approach for proteasome inhibitor-based therapy in WM. This trial is registered at www.clinicaltrials.gov as #NCT01470196., (© 2014 by The American Society of Hematology.)

Introduction: Qutenza (capsaicin) 8% patch is used to treat various neuropathic indications, including postherpetic neuralgia (PHN) and human immunodeficiency virus-associated neuropathy (HIV-AN)., Objectives: We conducted a meta-analysis of Qutenza studies to describe clinical phenomena of effects of Qutenza treatment better, such as onset and duration of pain relief, and the need for retreatments., Methods: The meta-analyses combined individual patient data (1313 participants with PHN and 801 with HIV-AN) from 7 completed randomized, double-blind, controlled studies. Studies had similar designs, and all used the Qutenza patch (8% capsaicin) and a low-dose control patch (0.04% capsaicin). A 30% response was defined as a ≥30% decrease in mean pain intensity score during week 2 to end of follow-up; complete pain relief was defined as an average pain intensity ≤1 during week 2 to end of follow-up. Duration of response was calculated using the data from long-term studies as the time from onset of response to offset of response, retreatment, or end of follow-up (whichever occurred first)., Results: Overall 44% of PHN and 41% of HIV-AN patients had a 30% response, and 11% and 7%, respectively, had complete pain relief 2 to 12 weeks after treatment with Qutenza. The mean (median) onset of response to Qutenza was 3.4 (1) days for PHN and 6.5 (4) days for HIV-AN (delayed due to an initial increase in discomfort). The mean (median) duration of response after 1 Qutenza treatment was 5 (3) months. Of the patients followed-up for 12 months, 40% PHN and 36% HIV-AN patients had a 30% response, and 9% and 10%, respectively, had complete pain relief from week 2 to end of follow-up., Conclusions: Qutenza is effective in a high proportion of patients. In patients who respond to Qutenza, analgesia starts within a few days of treatment and lasts on average 5 months.

Introduction: As part of the Centers for Disease Control and Prevention's monitoring and evaluation activities for influenza vaccines, we examined relationships between influenza vaccination and selected outcomes in the 2009-2010 and 2010-2011 influenza seasons in a claims-based data environment., Methods: We included patients with claims for trivalent influenza vaccine (TIV) and/or 2009 pandemic influenza A H1N1 vaccine (H1N1) during the 2009-2010 and 2010-2011 influenza seasons. Patients were followed for several pre-specified outcomes identified in claims. Seizures and Guillain-Barré Syndrome were selected a priori for medical record confirmation. We estimated incidence rate ratios (IRR) using a self-controlled risk interval (SCRI) or a historical comparison design. Outcomes with elevated IRRs, not selected a priori for medical record review, were further investigated with review of claims histories surrounding the outcome date to determine whether the potential event could be ruled-out or attributed to other causes based on the pattern of medical care., Results: In the 2009-2010 season, no significant increased risks for outcomes following H1N1 vaccination were observed. Following TIV administration, the IRR for peripheral nervous system disorders and neuropathy was slightly elevated (1.07, 95% CI: 1.01-1.13). The IRR for anaphylaxis following TIV was 28.55 (95% CI: 3.57-228.44). After further investigation of claims histories, the majority of potential anaphylaxis cases had additional claims around the time of the event indicating alternate explanatory factors or diagnoses. In the 2010-2011 season following TIV administration, a non-significant elevated IRR for anaphylaxis was observed with no other significant outcome findings., Conclusion: After claims history review, we ultimately found no increased outcome risk following administration of 998,881 TIV and 538,257 H1N1 vaccine doses in the 2009-2010 season, and 1,158,932 TIV doses in the 2010-2011 season., (Published by Elsevier Ltd.)

The integrin αvβ6 activates latent transforming growth factor-β (TGF-β) within the kidney and may be a target for the prevention of chronic allograft fibrosis after kidney transplantation. However, TGF-β also has known immunosuppressive properties that are exploited by calcineurin inhibitors (CNIs); thus, the net benefit of αvβ6 inhibition remains undetermined. To assess the acute impact of interference with αvβ6 on acute rejection, we tested a humanized αvβ6-specific monoclonal antibody (STX-100) in a randomized, double-blinded, placebo-controlled nonhuman primate renal transplantation study to evaluate whether αvβ6 blockade alters the risk of acute rejection during CNI-based immunosuppression. Rhesus monkeys underwent renal allotransplantation under standard CNI-based maintenance immunosuppression; 10 biopsy-confirmed rejection-free animals were randomized to receive weekly STX-100 or placebo. Animals treated with STX-100 experienced significantly decreased rejection-free survival compared to placebo animals (p = 0.049). Immunohistochemical analysis confirmed αvβ6 ligand presence, and αvβ6 staining intensity was lower in STX-100-treated animals (p = 0.055), indicating an apparent blockade effect of STX-100. LAP, LTBP-1 and TGF-β were all decreased in animals that rejected on STX-100 compared to those that rejected on standard immunosuppression alone, suggesting a relevant effect of αvβ6 blockade on local TGF-β. These data caution against the use of αvβ6 blockade to achieve TGF-β inhibition in kidney transplantation., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Qutenza® is a capsaicin patch used to treat peripheral neuropathic pain, including postherpetic neuralgia (PHN) and human immunodeficiency virus-associated neuropathy (HIV-AN). The Qutenza Clinical Trials Database has been assembled to more fully characterize the effects of Qutenza. We conducted a within-subject meta-analysis of Qutenza studies to further define the medication's efficacy profile across studies. The meta-analysis combined individual patient data from randomized, controlled studies of Qutenza in peripheral neuropathic pain (1458 subjects treated with approved doses of Qutenza or control patches; 1120 with PHN and 338 with HIV-AN). These 7 studies had similar designs and were performed with the high-dose 8% capsaicin Qutenza patch and a 0.04% low-dose control patch. The difference between treatment groups for the primary efficacy end point of percentage change from baseline to weeks 2 to 12 on pain intensity score was calculated. Response was defined as a ≥ 30% decrease in mean pain intensity score during weeks 2 to 12. The overall between-group difference in percentage change from baseline in pain intensity was 8.0% (95% confidence interval 4.6, 11.5; P<.001), which statistically significantly favored Qutenza over low-dose control. Qutenza superiority was demonstrated for both PHN and HIV-AN patients for the primary end point and the end point proportion of 30% pain reduction response, and for PHN patients for the end point of proportion of 50% pain reduction response. These results confirm that Qutenza is effective for the treatment of both PHN and HIV-AN compared to low-dose control patch., (Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Serum immunoglobulin (Ig) M monoclonal protein determined by electrophoresis (sIgM-MP) and total serum IgM (sIgM) by nephelometry are widely used for response assessment in Waldenström macroglobulinemia (WM), although have not been compared for predicting changes in underlying disease burden. We, therefore, compared these serum markers with changes in bone marrow (BM) and extramedullary disease for 73 patients who were rituximab naive and treated with a rituximab-containing regimen. By linear regression analysis, reductions in sIgM-MP and sIgM showed moderate correlation with BM disease involvement (r = 0.4051 and r = 0.4490, respectively), and did not differ from one another as estimators of BM disease response (P = .3745). Neither sIgM-MP nor sIgM showed a strong correlation with BM disease response in patients with low (<1000 mg/dL) or high (>5000 mg/dL) IgM levels and extramedullary disease response. sIgM-MP and sIgM, therefore, are comparable response markers in WM. Development of newer, more accurate surrogate response markers are needed to better delineate treatment outcomes in patients with WM and with low or high IgM levels, and extramedullary disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Unlabelled: Familial disease is common in Waldenström macroglobulinemia (WM). We examined the impact of familial disease status on treatment outcome in WM and observed that familial disease was associated with inferior outcomes. However patients with familial WM receiving a bortezomib-containing regimen showed improved treatment outcomes vs. those receiving non–bortezomib-containing regimens. Bortezomib-containing regimens may therefore represent a more optimal treatment approach for patients with familial WM., Background: We examined the impact of familial predisposition on treatment outcome in 135 patients with Waldenström macroglobulinemia (WM), 26.7% of whom had first- or second-degree relatives with a B-cell lymphoproliferative disorder., Patients and Methods: All patients were rituximab naive and received a rituximab-containing regimen. There were no significant differences in baseline characteristics between cohorts., Results: Overall response (93.9% vs. 75.0%; P = .029) and complete response/very good partial response (CR/VGPR) (23.2% vs. 16.7%; P < .0001), time to progression (TTP) (45.5 vs. 21 months; P = .015) and time to next therapy (TTNT) (50.0 vs. 33.0 months; P = .024) favored patients with sporadic WM. By multivariate analysis, familial predisposition was an independent marker for disease progression (hazard ratio, 0.554). Patients with familial but not sporadic disease exhibited better responses, including CR/VGPR attainment (P = .0006) and a trend for longer progression-free survival (> 33 vs. 20.6 months; P = .08), with bortezomib-containing therapy., Conclusion: The findings convey that familial predisposition is an important determinant of treatment outcome in WM. Prospective studies to confirm these observations are needed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Cardiovascular events are inconclusively associated with duloxetine use in clinical trials and spontaneous reports. This analysis of cardiovascular events in relation to duloxetine use within a large health insurance database provides further data on the association., Methods: This cohort study was conducted within a population with commercial health insurance. Adults with depression who initiated duloxetine were matched to separate cohorts of initiators of venlafaxine, selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants (TCAs), along with untreated patients with depression, and enrollees without depression. The cohorts were followed for cardiovascular events (acute myocardial infarction, sudden death, hypertensive crisis, arrhythmia, and coronary revascularization), which were identified through health insurance claims and confirmed upon review of underlying medical records. Proportional hazards and Poisson regression models were used for comparisons., Results: There were approximately 64,000 person-years of follow-up among all cohorts (including 17,386 person-years among 21,457 duloxetine initiators), yielding 279 cardiovascular events. Relative to duloxetine initiators, those without depression had lower rates of combined events (incidence rate ratio [IRR], 0.51; 95% confidence interval [CI], 0.32-0.81) and coronary revascularizations (IRR, 0.51; 95% CI 0.29-0.89). The IR of each of the cardiovascular outcomes did not differ across the other cohorts, even accounting for time since last duloxetine dispensing., Conclusion: The incidence of cardiovascular events did not differ among duloxetine initiators relative to other antidepressant comparators or those with untreated depression but was higher than those without depression, suggesting that depression itself (or associated morbidities) may affect the risk of cardiovascular events.

Elevated hepatic enzyme levels and hepatic injuries have been associated with duloxetine use in clinical trials and spontaneous reports, but the association of duloxetine with a broad spectrum of hepatic outcomes has not been assessed observationally. This cohort study of adult duloxetine initiators between 2004 and 2006 based on the Ingenix Research Data Mart involved 6 matched comparator cohorts, including 4 antidepressant initiator groups (venlafaxine, nefazodone, selective serotonin reuptake inhibitors, and tricyclic antidepressants), depressed but untreated patients, and individuals without depression. The cohorts were followed up for hepatic events, and proportional hazards regression compared duloxetine initiators with comparator cohorts, whereas Poisson regression compared duloxetine usage categories to account for changed therapy during follow-up. Approximately 64,000 person-years among 21,457 duloxetine initiators and comparator cohorts yielded 51 hepatic outcome events. Venlafaxine initiators (incidence rate ratio [IRR] = 0.34; 95% confidence interval [CI], 0.12-0.95) and the cohort without depression (IRR = 0.30; 95% CI, 0.10-0.93) had lower incidences of combined hepatic events than duloxetine initiators, whereas no other differences in hepatic events were observed for duloxetine initiators relative to selective serotonin reuptake inhibitors, tricyclic antidepressants, and untreated depressed patients. In as-treated analyses, relative to nonuse, current (IRR = 4.30; 95% CI, 1.45-12.81) and recent (IRR = 5.93; 95% CI, 1.63-21.55) duloxetine use was associated with greater incidence of less severe hepatic outcomes but not hepatic-related death and potential acute hepatic failure. Although duloxetine does not seem to increase the risk of hepatic-related death or acute hepatic failure, it may be associated with an increased risk of certain less severe hepatic events.

This study examined the outcome of 248 Waldenstrom macroglobulinaemia (WM) rituximab-naïve patients who responded to a rituximab-containing regimen. Eighty-six patients (35%) subsequently received maintenance rituximab (M-Rituximab). No differences in baseline characteristics, and post-induction categorical responses between cohorts were observed. The median rituximab infusions during induction was 6 for both cohorts; and 8 over a 2-year period for patients receiving M-Rituximab. Categorical responses improved in 16/162 (10%) of observed, and 36/86 (41·8%) of M-Rituximab patients respectively, following induction therapy (P < 0·0001). Both progression-free (56·3 vs. 28·6 months; P = 0·0001) and overall survival (Not reached versus 116 months; P = 0·0095) were longer in patients who received M-Rituximab. Improved progression-free survival was evident despite previous treatment status, induction with rituximab alone or in combination therapy (P ≤ 0·0001). Best serum IgM response was lower (P < 0·0001), and haematocrit higher (P = 0·001) for patients receiving M-Rituximab. Among patients receiving M-Rituximab, an increased number of infectious events were observed, but were mainly ≤ grade 2 (P = 0·008). The findings of this observational study suggest improved clinical outcomes following M-Rituximab in WM patients who respond to induction with a rituximab-containing regimen. Prospective studies aimed at clarifying the role of M-Rituximab therapy in WM patients are needed to confirm these findings., (© 2011 Blackwell Publishing Ltd.)

The incorporation of rituximab into various regimens has improved depth of response in Waldenstrom macroglobulinaemia (WM), though the impact of achieving better responses remains to be determined. We examined response depth on progression-free survival (PFS) in 159 rituximab-naïve WM patients who received rituximab-based therapy. The median follow-up was 33·5 months, and categorical responses were as follows: complete response (CR, 8·8%); very good partial response (VGPR, 13·2%); partial response (50%); minor response (18·9%); Non-Responders (8·8%). Sequencing for polymorphic variants of FCGR2A, FCGR2B, and FCGR3A was performed, and impact on response depth determined. Achievement of better categorical responses was incrementally associated with improved PFS (P < 0·0001). No separation was observed between CR and VGPR, and attainment of at least a VGPR was associated with improved time-to-progression. Neither age, serum IgM, haematocrit, platelet count, serum β(2) microglobulin, WM International Prognostic Scoring System score, and treatment group predicted for CR/VGPR. Polymorphisms at FCGR3A-48 and -158 were associated with improved categorical responses, particularly attainment of CR/VGPR (P ≤ 0·03). The attainment of CR/VGPR was associated with significantly longer PFS in rituximab-naïve WM patients undergoing rituximab-based therapy, and was predicted by polymorphisms in FCGR3A., (© 2011 Blackwell Publishing Ltd.)

As learning paradigms shift to student-centred active learning, development of effective skills in locating and retrieving information using electronic sources is integral to promoting lifelong learning. Recency of information that is evidence based is a critical factor in a dynamic field such as health. A changing demographic is evident among nursing students with greater numbers of mature age students who may not possess the computer skills often assumed with school leavers, and whose study preference is mostly by external mode. Development of interdisciplinary partnerships between faculties and librarians can provide the attributes and innovation of new and improved ways to better support student learning, whether or not students attend on campus. The Health Online Tutorial, an online database searching tool developed through a collaborative, interdisciplinary partnership at Charles Darwin University is one such example.

This paper discusses as study of mentoring and its relationship to nursing academics' scholarly productivity. A hermeneutic phenomenological approach was used to explore participants' experiences of mentoring and scholarship. Although all participants were well aware of the need to increase levels of scholarship, few had experienced the role modelling, guidance and leadership to assist them in meeting the expectations of the tertiary environment. While quality mentoring was viewed as a productive facilitator to improving levels of scholarly productivity, a supportive work environment with strong academic leadership was also considered an essential element in developing scholarship. Mentoring alone was considered unlikely to ameliorate any institutional issues, but rather, comprised one of a number of strategies. The picture that emerged from the study illustrates a discipline in transition in which a culture of mentoring is not well established, one that requires change not only within the discipline, but within tertiary institutions., (© 2010 Blackwell Publishing Asia Pty Ltd.)

Objective: To compare mothers' assessments of nutritional status with anthropometric measures and gain further insights into mothers' reasons for their judgment., Design: Each mother was asked to assess the nutritional status of her child and 2 other children and to compare all 3. Rates for "hits" and "misses" between mothers' assessment and physical anthropometry were analyzed using the binomial test. The rationale for the mothers' assessments was explored through open-ended questions., Setting: A rural clinic in an indigenous area of Mexico., Participants: 31 mothers of children 1-5 years of age., Main Outcome Measures: Physical anthropometry and mothers' assessments., Results: A significant proportion (P

We report the long-term outcome of a multicenter, prospective study examining fludarabine and rituximab in Waldenström macroglobulinemia (WM). WM patients with less than 2 prior therapies were eligible. Intended therapy consisted of 6 cycles (25 mg/m(2) per day for 5 days) of fludarabine and 8 infusions (375 mg/m(2) per week) of rituximab. A total of 43 patients were enrolled. Responses were: complete response (n = 2), very good partial response (n = 14), partial response (n = 21), and minor response (n = 4), for overall and major response rates of 95.3% and 86.0%, respectively. Median time to progression for all patients was 51.2 months and was longer for untreated patients (P = .017) and those achieving at least a very good partial response (P = .049). Grade 3 or higher toxicities included neutropenia (n = 27), thrombocytopenia (n = 7), and pneumonia (n = 6), including 2 patients who died of non-Pneumocystis carinii pneumonia. With a median follow-up of 40.3 months, we observed 3 cases of transformation to aggressive lymphoma and 3 cases of myelodysplastic syndrome/acute myeloid leukemia. The results of this study demonstrate that fludarabine and rituximab are highly active in WM, although short- and long-term toxicities need to be carefully weighed against other available treatment options. This study is registered at clinicaltrials.gov as NCT00020800.

This article describes the utilization of humidified high-flow oxygen therapy systems, which can comfortably deliver optimal humidified high-flow oxygen therapy, via nasal cannulae, at flow rates of up to 40 litres per minute to adult patients, in hospital or at home. The oxygen is saturated with water vapour at body temperature allowing flow to be well tolerated. First, to set the scene, three clinical scenarios are presented of patients nursed in intensive care, who suffered severe respiratory distress. Respiratory failure is explained, and the need for oxygen therapy set out. Alternative oxygen delivery devices and systems are then outlined, and an example of a high-flow system introduced. Set-up of the system is explained and the need for decontamination propounded. Finally, the benefits of the humidified high-flow oxygen system are exemplified, with particular reference to the critically ill patients presented here.

Nonexperimental studies suggest that individuals with higher selenium (Se) status are at decreased risk of cancer. The Nutritional Prevention of Cancer (NPC) study randomized 1,312 high-risk dermatology patients to 200-mcg/day of Se in selenized yeast or a matched placebo; selenium supplementation decreased the risk of lung, colon, prostate, and total cancers but increased the risk of nonmelanoma skin cancer. In this article, we report on a small substudy in Macon, GA, which began in 1989 and randomized 424 patients to 400-mcg/day of Se or to matched placebo. The subjects from both arms had similar baseline Se levels to those treated by 200 mcg, and those treated with 400-mcg attained plasma Se levels much higher than subjects treated with 200 mcg. The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25%; however, 400-mcg/day of Se had no effect on total cancer incidence.