Antibodies against p53 are associated with poor prognosis of colorectal cancer.

Mutation of the p53 gene is a common event in colorectal cancer. This alteration can result in cellular accumulation of p53 and may also induce p53 antibodies. Accumulation of p53 in tumour cells has been associated with poor prognosis of colorectal cancer. We tested preoperative sera from 255 patients with colorectal cancer by enzyme-linked immunosorbent assay (ELISA). A total of 70.2% had reactivity that was higher than the 'low' control serum. Employing a cut-off level of 10% of the 'high' control sample, 25.5% of the patients were positive for p53 antibodies. The presence of p53 antibodies correlated with the following prognostic factors: histological differentiation grade, shape of the tumour, and tumour invasion into blood vessels. Patients with p53 antibodies were shown to have decreased survival and decreased disease-free survival. Specifically for patients with cancer stage A and B1 the presence of p53 antibodies selected a subgroup with poor prognosis

Ferrule-top nanoindenter: An optomechanical fiber sensor for nanoindentation

Ferrule-top probes are self-aligned all-optical devices obtained by fabricating a cantilever on the top of a ferruled optical fiber. This approach has been proven to provide a new platform for the realization of small footprint atomic force microscopes (AFMs) that adapt well to utilization outside specialized laboratories [D. Chavan, Rev. Sci. Instrum. 81, 123702 (2010)10.1063/1.3516044; D. Chavan, Rev. Sci. Instrum. 82, 046107 (2011)10.1063/1.3579496]. In this paper we now show that ferrule-top cantilevers can be also used to develop nanoindenters. Our instrument combines the sensitivity of commercial AFM-based indentation with the ease-of-use of more macroscopic instrumented indenters available today on the market. Furthermore, the all-optical design allows smooth operations also in liquids, where other devices are much more limited and often provide data that are difficult to interpret. This study may pave the way to the implementation of a new generation user-friendly nanoindenters for the measurement of the stiffness of samples in material sciences and medical research. © 2012 American Institute of Physics

HLA-matched platelet transfusions are effective only in refractory patients with positive HLA antibody screening

BACKGROUND Recipients of platelet transfusions with 1-hour corrected count increments (1hCCIs) of 7.5 or less on two subsequent platelet transfusions with random platelets may benefit from human leukocyte antigen (HLA)-matched platelet concentrates. We aimed to quantify the efficacy of HLA-matched platelets concentrates expressed in 1hCCIs. METHODS We performed a cohort study among consecutive refractory patients who received HLA-matched platelet concentrates in the Netherlands between 1994 and 2017. We performed mixed-model linear regression comparing 1hCCIs after HLA split-antigen-matched transfusions with 1hCCIs after HLA-mismatched transfusions, adjusted for within-patient correlations. A donor-to-patient match was categorized as a split-match if all donor HLA-A and -B antigens were present in the patient as well; that is, donor and patient were HLA identical or compatible. Subgroup analyses were performed for patients with positive or negative HLA antibody screens. Finally, the additional effect of ABO mismatches on 1hCCIs was investigated. RESULTS The 1hCCI after an HLA-matched transfusion was 14.09 (95% reference interval, 1.13-29.89). This was 1.94 (95% confidence interval [CI], 0.74-3.15) higher than 1hCCI after HLA-mismatched transfusions. In patients with negative HLA antibody screening tests, HLA matching did not affect 1hCCIs. Conditional on HLA matching, 1hCCIs decreased by 3.70 (95% CI, -5.22 to -2.18) with major ABO mismatches. CONCLUSION Matched platelet concentrates yielded maximal 1hCCIs, whereas mismatched transfusions still resulted in adequate increments. There is no indication for HLA-matched platelets in patients with negative antibody screens

Association of Timing of Plasma Transfusion With Adverse Maternal Outcomes in Women With Persistent Postpartum Hemorrhage

IMPORTANCE Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the association of early plasma transfusion with maternal outcomes. OBJECTIVE To compare the incidence of adverse maternal outcomes among women who received plasma during the first 60 minutes of persistent PPH vs women who did not receive plasma for similarly severe persistent PPH. DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study used a consecutive sample of women with persistent PPH, defined as PPH refractory to first-line measures to control bleeding, between January 1, 2011, and January 1, 2013. Time-dependent propensity score matching was used to select women who received plasma during the first 60 minutes of persistent PPH and match each of them with a woman who had shown the same severity and received the same treatment of PPH but who had not received plasma at the moment of matching. Transfusions were not guided by coagulation tests. Statistical analysis was performed from June 2018 to June 2019. EXPOSURES Transfusion of plasma during the first 60 minutes of persistent PPH vs no or later plasma transfusion. MAIN OUTCOMES AND MEASURES Incidence of adverse maternal outcomes, defined as a composite of death, hysterectomy, or arterial embolization. RESULTS This study included 1216 women (mean [SD] age, 31.6 [5.0] years) with persistent PPH, of whom 932 (76.6%) delivered vaginally and 780 (64.1%) had PPH caused by uterine atony. Seven women (0.6%) died because of PPH, 62 women (5.1%) had a hysterectomy, and 159 women (13.1%) had arterial embolizations. Among women who received plasma during the first 60 minutes of persistent PPH, 114 women could be matched with a comparable woman who had not received plasma at the moment of matching. The incidence of adverse maternal outcomes was similar between the women, with adverse outcomes recorded in 24 women (21.2%) who received early plasma transfusion and 23 women (19.9%) who did not receive early plasma transfusion (odds ratio, 1.09; 95% CI, 0.57-2.09). Results of sensitivity analyses were comparable to the primary results. CONCLUSIONS AND RELEVANCE In this cohort study, initiation of plasma transfusion during the first 60 minutes of persistent PPH was not associated with adverse maternal outcomes compared with no or later plasma transfusion, independent of severity of PPH

Transition from School to University Mathematics: Manifestations of Unresolved Commognitive Conflict in First Year Students’ Examination Scripts

We explore the transition from school to university through a commognitive (Sfard 2008) analysis of twenty-two students’ examination scripts from the end of year examination of a first year, year-long module on Sets, Numbers, Proofs and Probability in a UK mathematics department. Our analysis of the scripts relies on a preliminary analysis of the tasks and the lecturers’ (also exam setters’) assessment practices, and focuses on manifestations of unresolved commognitive conflict in students’ engagement with the tasks. Here we note four such manifestations concerning the students’ identification of and consistent work with: the appropriate numerical context of the examination tasks; the visual mediators and the rules of school algebra and Set Theory discourses; the visual mediators of the Probability and Set Theory discourses; and, with the visual mediators and rules of the Probability Theory discourse. Our analysis suggests that, despite lecturers’ attempts to assist students towards a smooth transition to the different discourses of university mathematics, students’ errors at the final examination reveal unresolved commognitive conflicts. A pedagogical implication of our analysis is that a more explicit and systematic presentation of the distinctive differences between these discourses, along with facilitation of the flexible moves between them, is needed

What is case management in palliative care? An expert panel study

Contains fulltext : 110207.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Case management is a heterogeneous concept of care that consists of assessment, planning, implementing, coordinating, monitoring, and evaluating the options and services required to meet the client's health and service needs. This paper describes the result of an expert panel procedure to gain insight into the aims and characteristics of case management in palliative care in the Netherlands. METHODS: A modified version of the RAND(R)/University of California at Los Angeles (UCLA) appropriateness method was used to formulate and rate a list of aims and characteristics of case management in palliative care. A total of 76 health care professionals, researchers and policy makers were invited to join the expert panel, of which 61% participated in at least one round. RESULTS: Nine out of ten aims of case management were met with agreement. The most important areas of disagreement with regard to characteristics of case management were hands-on nursing care by the case manager, target group of case management, performance of other tasks besides case management and accessibility of the case manager. CONCLUSIONS: Although aims are agreed upon, case management in palliative care shows a high level of variability in implementation choices. Case management should aim at maintaining continuity of care to ensure that patients and those close to them experience care as personalised, coherent and consistent

Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study

Objective To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease. Design Registry based observational study. Setting 74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021 Participants All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients). Main outcome measures Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease. Results Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07). Conclusions In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research