Density functional electronic spectrum of the CuO−6−10Cu O_{-6}^{-10} cluster and possible local Jahn-Teller distorsions in the La-Ba-Cu-O superconductor

We present a density functional theory (DFT) calculation in the generalized gradient approximation to study the possibility for the existence of Jahn-Teller (JT) or pseudo Jahn-Teller (PJT) type local distortions in the La-Ba-Cu-O superconducting system. We performed the calculation and correspondingly group theory classification of the electronic ground state of the CuO${_{6}}^{-10}$ elongated octahedra cluster, immersed in a background simulating the superconductor. Part of the motivation to do this study is that the origin of the apical deformation of the CuO${_{6}}^{-10}$ cluster is not due to a pure JT effect, having therefore a non {\it a priori} condition to remove the degeneracy of the electronic ground state of the parent regular octahedron. We present a comparative analysis of the symmetry classified electron spectrum with previously reported results using unrestricted Hartree-Fock calculations (UHF). Both the DFT and UHF calculations produced a non degenerate electronic ground state, not having therefore the necessary condition for a pure JT effect. However, the appearance of a degenerate E$_{g}$ state near to the highest occupied molecular orbital in the DFT calculation, suggests the possibility for a PJT effect responsible for a local distortion of the oxidized CuO$_{6}^{-9}$ cluster.Comment: 12 pages, 3 figures, submitted to International Journal of Modern Physics B (IJMPB

Bosutinib plus capecitabine for selected advanced solid tumours: results of a phase 1 dose-escalation study

Background: This phase 1 study evaluated the maximum tolerated dose (MTD), safety, and efficacy of bosutinib (competitive Src/Abl tyrosine kinase inhibitor) plus capecitabine. Methods: Patients with locally advanced/metastatic breast, pancreatic, or colorectal cancers; cholangiocarcinoma; or glioblastoma received bosutinib plus capecitabine at eight of nine possible dose combinations using an ‘up-down' design to determine the toxicity contour of the combination. Results: Among 32 enrolled patients, none of the 9 patients receiving MTD (bosutinib 300 mg once daily plus capecitabine 1000 mg m−2 twice daily) experienced dose-limiting toxicities (DLTs). Overall, 2 out of 31 (6%) evaluable patients experienced DLTs (grade 3 neurologic pain (n=1); grade 3 pruritus/rash and increased alanine aminotransferase (n=1)). Most common treatment-related adverse events (AEs) were diarrhoea, nausea, vomiting, palmar-plantar erythrodysesthesia (PPE), fatigue; most frequent grade 3/4 AEs: PPE, fatigue, and increased alanine/aspartate aminotransferase. Although diarrhoea was common, 91% of affected patients experienced maximum grade 1/2 events that resolved. Best overall confirmed partial response or stable disease >24 weeks (all tumour types) was observed in 6 and 13% of patients. Conclusions: In this population of patients with advanced solid tumours, bosutinib plus capecitabine demonstrated a safety profile similar to that previously reported for bosutinib or capecitabine monotherapy; limited efficacy was observed

Factors related to abdominal pain in gastroparesis: contrast to patients with predominant nausea and vomiting

Background Factors associated with abdominal pain in gastroparesis are incompletely evaluated and comparisons of pain vs other symptoms are limited. This study related pain to clinical factors in gastroparesis and contrasted pain/discomfort‐ with nausea/vomiting‐predominant disease. Methods Clinical and scintigraphy data were compared in 393 patients from seven centers of the NIDDK Gastroparesis Clinical Research Consortium with moderate‐severe (Patient Assessment of Upper Gastrointestinal Disorders Symptoms [ PAGI ‐ SYM ] score ≥3) vs none‐mild ( PAGI ‐ SYM  < 3) upper abdominal pain and predominant pain/discomfort vs nausea/vomiting. Key Results Upper abdominal pain was moderate‐severe in 261 (66%). Pain/discomfort was predominant in 81 (21%); nausea/vomiting was predominant in 172 (44%). Moderate‐severe pain was more prevalent with idiopathic gastroparesis and with lack of infectious prodrome (P ≤ 0.05) and correlated with scores for nausea/vomiting, bloating, lower abdominal pain/discomfort, bowel disturbances, and opiate and antiemetic use (P < 0.05), but not gastric emptying or diabetic neuropathy or control. Gastroparesis severity, quality of life, and depression and anxiety were worse with moderate‐severe pain (P ≤ 0.008). Factors associated with moderate‐severe pain were similar in diabetic and idiopathic gastroparesis. Compared to predominant nausea/vomiting, predominant pain/discomfort was associated with impaired quality of life, greater opiate, and less antiemetic use (P < 0.01), but similar severity and gastric retention. Conclusions & Inferences Moderate‐severe abdominal pain is prevalent in gastroparesis, impairs quality of life, and is associated with idiopathic etiology, lack of infectious prodrome, and opiate use. Pain is predominant in one fifth of gastroparetics. Predominant pain has at least as great an impact on disease severity and quality of life as predominant nausea/vomiting.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97520/1/nmo12091.pd

Epidemiology of pertussis in two Ibero-American countries with different vaccination policies: lessons derived from different surveillance systems

Background Pertussis is a re-emerging disease worldwide despite its high vaccination coverage. European and Latin-American countries have used different surveillance and vaccination policies against pertussis. We compared the epidemiology of this disease in two Ibero-American countries with different vaccination and surveillance policies. Methods We compared the epidemiology of pertussis in Spain and the Dominican Republic (DR). We present a 10-year observational study of reported pertussis based on suspected and/or probable cases of pertussis identified by the national mandatory reporting system in both countries between 2005 and 2014. Both countries have a similar case definition for pertussis surveillance, although Spain applies laboratory testing, and uses real time PCR and/or culture for case confirmation while in DR only probable and/or suspected cases are reported. We analyzed incidence, hospitalization, case-fatality rates, mortality and vaccination coverage. Results The average annual incidence in children aged <1 year was 3.40/100,000 population in Spain and 12.15/100,000 in DR (p = 0.01). While the incidence in DR was generally higher than in Spain, in 2011 it was six times higher in Spain than in DR. The highest infant mortality in Spain was 0.017/100,000 in 2011, and the highest in DR was 0.08/100,000 in 2014 (p = 0.01). The proportion of hospitalized cases per year among children <1 year varied between 22.0% and 93.7% in Spain, and between 1.1% and 29.4% in DR (p = 0.0002), while mortality varied from 0 to 0.017 and 0 to 0.08 per 100,000 population in Spain and DR, respectively (p = 0.001). Vaccination coverage was 96.5% in Spain and 82.2% in DR (p = 0.001). Conclusions Pertussis is a public health problem in both countries. Surveillance, prevention and control measures should be improved, especially in DR. Current vaccination programs are not sufficient for preventing continued pertussis transmission, even in Spain which has high vaccination coverag

Increased Glycemic Variability Is Independently Associated With Length of Stay and Mortality in Noncritically Ill Hospitalized Patients

OBJECTIVE To investigate the association between glycemic variability (GV) and both length of stay (LOS) and 90-day mortality in noncritically ill hospitalized patients. RESEARCH DESIGN AND METHODS This study retrospectively analyzed 4,262 admissions to the general medicine or surgery services during a 2 year period. Patients with point-of-care glucose monitoring and a minimum of two glucose values per day on average were selected. GV was assessed by SD and coefficient of variation (CV). Data were analyzed with linear and logistic multivariate regression analysis in separate models for SD and CV. Analysis was performed with generalized estimating equations to adjust for correlation between multiple admissions in some individual cases. RESULTS After exclusions, 935 admissions comprised the sample. Results of adjusted analysis indicate that for every 10 mg/dL increase in SD and 10–percentage point increase in CV, LOS increased by 4.4 and 9.7%, respectively. Relative risk of death in 90 days also increased by 8% for every 10-mg/dL increase in SD. These associations were independent of age, race, service of care (medicine or surgery), previous diagnosis of diabetes, HbA1c, BMI, the use of regular insulin as a sole regimen, mean glucose, and hypoglycemia occurrence during the hospitalization. CONCLUSIONS Our results indicate that increased GV during hospitalization is independently associated with longer LOS and increased mortality in noncritically ill patients. Prospective studies with continuous glucose monitoring are necessary to investigate this association thoroughly and to generate therapeutic strategies targeted at decreasing GV. Inpatient hyperglycemia is common, and it has been associated with increased morbidity and mortality in patients with and without diabetes (1–7). In the intensive care unit (ICU) setting, hypoglycemia has also been independently associated with a significant increase in mortality (8–10). Recently, a third metric of glucose control, known as glycemic variability (GV), has been proposed to be additionally implicated in the disease-associated process of dysglycemia (11). GV refers to fluctuations of blood glucose values around the mean and has been posited as a novel marker for poor glycemic control (12,13). In vitro and human studies suggest that high GV leads to greater oxidative stress than does sustained hyperglycemia (14,15). Studies of ICU patients have consistently demonstrated that increased GV is independently associated with higher mortality (16–19). Notably, results from a large multicenter study concluded that GV was a stronger predictor of ICU mortality than was mean glucose concentrations (20). Although there is no consensus as to the best method to determine GV in hospitalized patients, the use of SD of glucose values has been well validated by previous ICU studies (16,20). Coefficient of variation (CV) has also been suggested as a strong independent index for measuring GV because it corrects for mean glucose levels (21,22). Despite substantial scientific evidence from the ICU, no previous studies have investigated the association between GV and clinical outcomes in patients admitted to the general medical and surgical wards. The purpose of this study was therefore to investigate the association between GV and length of stay (LOS) and 90-day mortality in noncritically ill hospitalized patients. We hypothesize that increased GV in this setting is associated with increased LOS and mortality

The relationship between maternal education and mortality among women giving birth in health care institutions: Analysis of the cross sectional WHO Global Survey on Maternal and Perinatal Health

Background: Approximately one-third of a million women die each year from pregnancy-related conditions. Three-quarters of these deaths are considered avoidable. Millennium Development Goal five calls for a reduction in maternal mortality and the establishment of universal access to high quality reproductive health care. There is evidence of a relationship between lower levels of maternal education and higher maternal mortality. This study examines the relationship between maternal education and maternal mortality among women giving birth in health care institutions and investigates the association of maternal age, marital status, parity, institutional capacity and state-level investment in health care with these relationships.Methods: Cross-sectional information was collected on 287,035 inpatients giving birth in 373 health care institutions in 24 countries in Africa, Asia and Latin America, between 2004-2005 (in Africa and Latin America) and 2007-2008 (in Asia) as part of the WHO Global Survey on Maternal and Perinatal Health. Analyses investigated associations between indicators measured at the individual, institutional and country level and maternal mortality during the intrapartum period: from admission to, until discharge from, the institution where women gave birth. There were 363 maternal deaths.Results: In the adjusted models, women with no education had 2.7 times and those with between one and six years of education had twice the risk of maternal mortality of women with more than 12 years of education. Institutional capacity was not associated with maternal mortality in the adjusted model. Those not married or cohabiting had almost twice the risk of death of those who were. There was a significantly higher risk of death among those aged over 35 (compared with those aged between 20 and 25 years), those with higher numbers of previous births and lower levels of state investment in health care. There were also additional effects relating to country of residence which were not explained in the model.Conclusions: Lower levels of maternal education were associated with higher maternal mortality even amongst women able to access facilities providing intrapartum care. More attention should be given to the wider social determinants of health when devising strategies to reduce maternal mortality and to achieve the increasingly elusive MDG for maternal mortality

Analysis of Nurse and Patient Preferences for Pre-Filled Pen Devices for Self-Injection of Highly Purified Human Menopausal Gonadotropin (HP-hMG, MENOPUR®)

PURPOSE: This study aimed to identify the most important attributes for a gonadotropin pen as perceived by assisted reproductive technology (ART) patients and fertility nurses, and to examine how well a prototype HP-hMG (MENOPUR PATIENTS AND METHODS: This market research study incorporated a two-part survey with respondents (N=221) from Poland, Spain and the UK. Respondents included patients (n=141) who consulted a fertility specialist in the previous 2 years, and fertility nurses (n=80) who assisted in at least 75 ART cycles/year. Patients were divided into two subgroups depending on their experience with ART (experienced and naïve). Key attributes for an injection pen, as perceived by patients and nurses, were assessed via an online survey and ranked by their relative importance using Anchored Maximum Difference Scaling. After performing a dummy injection, respondents compared the attributes of an unbranded prototype pen against the key attributes identified. RESULTS: Across all survey respondents, the ability to correct the dialed dose was considered to be the most important product attribute of a gonadotropin pen. Confidence in the patient\u27s ability to inject correctly at home was also identified as a key attribute, considered by both nurses and naïve patients as extremely high. When considering the prototype pen device, almost all study respondents reported a positive experience (99%) with 72% rating it as very good . The prototype pen was perceived to possess the key attributes considered important for a gonadotropin pen by patients and nurses, including correcting the dose, the ability to self-inject safely and correctly, ease of preparation and use, and an injection which appeared to be as painless as possible. CONCLUSION: The prototype pen was found to perform well across all key attributes, especially those considered most important in gonadotropin pens, suggesting that it is a user-friendly option for patients undergoing ART

Analysis of Nurse and Patient Preferences for Pre-Filled Pen Devices for Self-Injection of Highly Purified Human Menopausal Gonadotropin (HP-hMG, MENOPURR

PURPOSE: This study aimed to identify the most important attributes for a gonadotropin pen as perceived by assisted reproductive technology (ART) patients and fertility nurses, and to examine how well a prototype HP-hMG (MENOPUR PATIENTS AND METHODS: This market research study incorporated a two-part survey with respondents (N=221) from Poland, Spain and the UK. Respondents included patients (n=141) who consulted a fertility specialist in the previous 2 years, and fertility nurses (n=80) who assisted in at least 75 ART cycles/year. Patients were divided into two subgroups depending on their experience with ART (experienced and naïve). Key attributes for an injection pen, as perceived by patients and nurses, were assessed via an online survey and ranked by their relative importance using Anchored Maximum Difference Scaling. After performing a dummy injection, respondents compared the attributes of an unbranded prototype pen against the key attributes identified. RESULTS: Across all survey respondents, the ability to correct the dialed dose was considered to be the most important product attribute of a gonadotropin pen. Confidence in the patient\u27s ability to inject correctly at home was also identified as a key attribute, considered by both nurses and naïve patients as extremely high. When considering the prototype pen device, almost all study respondents reported a positive experience (99%) with 72% rating it as very good . The prototype pen was perceived to possess the key attributes considered important for a gonadotropin pen by patients and nurses, including correcting the dose, the ability to self-inject safely and correctly, ease of preparation and use, and an injection which appeared to be as painless as possible. CONCLUSION: The prototype pen was found to perform well across all key attributes, especially those considered most important in gonadotropin pens, suggesting that it is a user-friendly option for patients undergoing ART

Post-translational regulation contributes to the loss of LKB1 expression through SIRT1 deacetylase in osteosarcomas

background: The most prevalent form of bone cancer is osteosarcoma (OS), which is associated with poor prognosis in case of metastases formation. Mice harbouring liver kinase B1 (LKB1+/−) develop osteoblastoma-like tumours. Therefore, we asked whether loss of LKB1 gene has a role in the pathogenesis of human OS. methods: Osteosarcomas (n=259) were screened for LKB1 and sirtuin 1 (SIRT1) protein expression using immunohistochemistry and western blot. Those cases were also screened for LKB1 genetic alterations by next-generation sequencing, Sanger sequencing, restriction fragment length polymorphism and fluorescence in situ hybridisation approaches. We studied LKB1 protein degradation through SIRT1 expression. MicroRNA expression investigations were also conducted to identify the microRNAs involved in the SIRT1/LKB1 pathway. results: Forty-one per cent (106 out of 259) OS had lost LKB1 protein expression with no evident genetic anomalies. We obtained evidence that SIRT1 impairs LKB1 protein stability, and that SIRT1 depletion leads to accumulation of LKB1 in OS cell lines resulting in growth arrest. Further investigations revealed the role of miR-204 in the regulation of SIRT1 expression, which impairs LKB1 stability. conclusions: We demonstrated the involvement of sequential regulation of miR-204/SIRT1/LKB1 in OS cases and showed a mechanism for the loss of expression of LKB1 tumour suppressor in this malignancy