Clinical utility of a molecular test in adjuvant treatment decision making in women with endocrine-sensitive early stage breast cancer: a retrospective, single center one year experience

Background. Molecular tests for breast cancer (BC) risk assessment are reimbursed by health insurances in Switzerland since the beginning of year 2015. The main current role of these tests is to help oncologists to decide about the usefulness of adjuvant chemotherapy in patients with early stage endocrine-sensitive and human epidermal growth factor receptor 2 (HER2)-negative BC. These gene expression signatures aim at predicting the risk of recurrence in this subgroup. One of them (OncotypeDx/OT) also predicts distant metastases rate with or without the addition of cytotoxic chemotherapy to endocrine therapy. The clinical utility of these tests -in addition to existing so-called "clinico-pathological" prognostic and predictive criteria (e.g. stage, grade, biomarkers status)-is still debated. We report a single center one year experience of the use of one molecular test (OT) in clinical decision making. Methods. We extracted from the CHUV Breast Cancer Center data base the total number of BC cases with estrogen-receptor positive (ER+), HER2-negative early breast cancer (node negative (pN0) disease or micrometastases in up to 3 lymph nodes) operated between September 2014 and August 2015. For the cases from this group in which a molecular test had been decided by the tumor board, we collected the clinicopathologic parameters, the initial tumor board decision, and the final adjuvant systemic therapy decision. Results. A molecular test (OT) was done in 12.2% of patients with ER + HER2 negative early BC. The median age was 57.4 years and the median invasive tumor size was 1.7 cm. These patients were classified by ODX testing (Recurrence Score) into low-, intermediate-, and high risk groups, respectively in 27.2%, 63.6% and 9% of cases. Treatment recommendations changed in 18.2%, predominantly from chemotherapyendocrine therapy to endocrine treatment alone. Of 8 patients originally recommended chemotherapy, 25% were recommended endocrine treatment alone after receiving the Recurrence Score result. Conclusions. Though reimbursed by health insurances since January 2015, molecular tests are used moderately in our institution as per the decision of the multidisciplinary tumor board. It's mainly used to obtain a complementary confirmation supporting the decision of no chemotherapy. The OncotypeDx Recurrence Score results were in the intermediate group in 66% of the 9 tested cases but contributed to avoid chemotherapy in 2 patients during the last 12 months.

Measuring individuals' response quality in self-administered psychological tests : an introduction to Gendre's functional method

The functional method is a new test theory using a new scoring method that assumes complexity in test structure, and thus takes into account every correlation between factors and items. The main specificity of the functional method is to model test scores by multiple regression instead of estimating them by using simplistic sums of points. In order to proceed, the functional method requires the creation of hyperspherical measurement space, in which item responses are expressed by their correlation with orthogonal factors. This method has three main qualities. First, measures are expressed in the absolute metric of correlations; therefore, items, scales and persons are expressed in the same measurement space using the same single metric. Second, factors are systematically orthogonal and without errors, which is optimal in order to predict other outcomes. Such predictions can be performed to estimate how one would answer to other tests, or even to model one's response strategy if it was perfectly coherent. Third, the functional method provides measures of individuals' response validity (i.e., control indices). Herein, we propose a standard procedure in order to identify whether test results are interpretable and to exclude invalid results caused by various response biases based on control indices.

Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases.

BACKGROUND: Hyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin). OBJECTIVE: We sought to characterize the genetic cause and clinical spectrum of Hz/Hc. METHODS: Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. PSTPIP1-pyrin interactions were analyzed by means of immunoprecipitation and Western blotting. A structural model of the PSTPIP1 dimer was generated. Cytokine profiles were analyzed by using the multiplex immunoassay, and MRP8/14 serum concentrations were analyzed by using an ELISA. RESULTS: Thirteen patients were heterozygous for a missense mutation in the PSTPIP1 gene, resulting in a p.E250K mutation, and 1 carried a mutation resulting in p.E257K. Both mutations substantially alter the electrostatic potential of the PSTPIP1 dimer model in a region critical for protein-protein interaction. Patients with Hz/Hc have extremely high MRP8/14 concentrations (2045 ± 1300 μg/mL) compared with those with PAPA syndrome (116 ± 74 μg/mL) and have a distinct clinical phenotype. A specific cytokine profile is associated with Hz/Hc. Hz/Hc mutations altered protein binding of PSTPIP1, increasing interaction with pyrin through phosphorylation of PSTPIP1. CONCLUSION: Mutations resulting in charge reversal in the y-domain of PSTPIP1 (E→K) and increased interaction with pyrin cause a distinct autoinflammatory disorder defined by clinical and biochemical features not found in patients with PAPA syndrome, indicating a unique genotype-phenotype correlation for mutations in the PSTPIP1 gene. This is the first inborn autoinflammatory syndrome in which inflammation is driven by uncontrolled release of members of the alarmin family.

Outcomes After Liver Resection for Hepatic Alveolar Echinococcosis: A Single-Center Cohort Study.

BACKGROUND: Switzerland is a region in which alveolar echinococcosis (AE) is endemic. Studies evaluating outcomes after liver resection (LR) for AE are scarce. The aim of this study was to assess the short- and long-term outcomes of AE patients after LR in a single tertiary referral center. METHODS: We retrospectively analyzed data pertaining to all patients with liver AE who were treated with LR at our institution between January 1992 and December 2013. Patient demographics, intraoperative data, extent of LR procedures (major vs. minor LR), postoperative outcomes, and negative histological margin (R0) resection rate were recorded in a database. Recurrence rates after LR were analyzed. RESULTS: LR was performed in 59 patients diagnosed with hepatic AE (56 complete surgeries, 3 reduction surgeries). Postoperative morbidity and mortality were observed in 34 % (25 % grade I-II, 9 % grade III-IV) and 2 % of the patients, respectively. R0 (complete) resection rate was 71 % (n = 42), and R1/R2 resection rate was 29 % (n = 17). Extra-hepatic recurrence occurred in 1 case (lung) after R0 resection. In cases of R1/R2 resection, 7 intra-hepatic disease progressions occurred with a median time of 10 months (IQR 6-11 months). Long-term (more than 1 year) benzimidazole treatment stabilized the disease in 64 % (9/14) of patients with R1 status. The overall survival rate was 97 %. CONCLUSIONS: Liver AE can be safely and definitively treated with LR, provided that R0 resection is achieved. In cases of R1 resection, benzimidazole therapy seems to be effective in stabilizing the intra-hepatic disease and preventing extra-hepatic recurrence.

Hoitotyön opettajan osaaminen

The purpose of this study was to evaluate the competence of nurse teachers, who are teaching nursing at polytechnic level in Finland. The following research questions were framed for the study: What kind of evaluation nurse teachers of their nursing competence, teaching skills, evaluation skills, personality factors and relationships with students. The data were collected by a questionnaire (A Tool for Evaluation of Requirements of Nurse Teacher, ERNT). The questionnaire regarded background factors and 20 statements divided in five categories. The five competence categories were: Nursing competence, Teaching skills, Evaluation skills, Personality factors and Relationships with students. The evaluation scale was a 5-point Likert-scale. The respondents were nurse teachers, teacher for emergency nursing, public health nurse and midwifery teachers from all polytechnics in Finland. Response rate to the questionnaire was 46 % (n=342). The data were analysed by using descriptive statistics. Mean scores and standard deviations for each item were calculated. Category scores were obtained by summing scores of all items within a category. The results of this study showed that nurse teacher evaluated their competence on a high level. Concerning the category Relationships with students (mean 4.61, standard deviation 0.71) they got the highest averages. The lowest scores were gained regarding the requirements associated with teaching skills (mean 4.30, standard deviation 0.82). Concerning a single question, the best score was achieved in ability to take students seriously (mean 4.66, standard deviation 0.71) and the lowest score was achieved for their guidance of students to advance in decision making (mean 4.15, Std 0.69). The nurse teachers evaluated themselves with relatively high scores concerning competence categories as a hole. In future it is important to study nurse teacher competence with students or authorities of health service.

Improving the performance of the single-dish Cherenkov telescope MAGIC through the use of signal timing

The Cherenkov light flashes produced by Extensive Air Showers are very short in time. A high bandwidth and fast digitizing readout, therefore, can minimize the influence of the background from the light of the night sky, and improve the performance in Cherenkov telescopes. The time structure of the Cherenkov image can further be used in single-dish Cherenkov telescopes as an additional parameter to reduce the background from unwanted hadronic showers. A description of an analysis method which makes use of the time information and the subsequent improvement on the performance of the MAGIC telescope (especially after the upgrade with an ultra fast 2 GSamples/s digitization system in February 2007) will be presented. The use of timing information in the analysis of the new MAGIC data reduces the background by a factor two, which in turn results in an enhancement of about a factor 1.4 of the flux sensitivity to point-like sources, as tested on observations of the Crab Nebula.

A 14-item Mediterranean diet assessment tool and obesity indexes among high-risk subjects: the PREDIMED trial

Objective: Independently of total caloric intake, a better quality of the diet (for example, conformity to the Mediterranean diet) is associated with lower obesity risk. It is unclear whether a brief dietary assessment tool, instead of full-length comprehensive methods, can also capture this association. In addition to reduced costs, a brief tool has the interesting advantage of allowing immediate feedback to participants in interventional studies. Another relevant question is which individual items of such a brief tool are responsible for this association. We examined these associations using a 14-item tool of adherence to the Mediterranean diet as exposure and body mass index, waist circumference and waist-to-height ratio (WHtR) as outcomes. Design: Cross-sectional assessment of all participants in the"PREvención con DIeta MEDiterránea" (PREDIMED) trial. Subjects: 7,447 participants (55-80 years, 57% women) free of cardiovascular disease, but with either type 2 diabetes or $3 cardiovascular risk factors. Trained dietitians used both a validated 14-item questionnaire and a full-length validated 137-item food frequency questionnaire to assess dietary habits. Trained nurses measured weight, height and waist circumference. Results: Strong inverse linear associations between the 14-item tool and all adiposity indexes were found. For a two-point increment in the 14-item score, the multivariable-adjusted differences in WHtR were 20.0066 (95% confidence interval,- 0.0088 to 20.0049) for women and-0.0059 (-0.0079 to-0.0038) for men. The multivariable-adjusted odds ratio for a WHtR.0.6 in participants scoring $10 points versus #7 points was 0.68 (0.57 to 0.80) for women and 0.66 (0.54 to 0.80) for men. High consumption of nuts and low consumption of sweetened/carbonated beverages presented the strongest inverse associations with abdominal obesity. Conclusions: A brief 14-item tool was able to capture a strong monotonic inverse association between adherence to a good quality dietary pattern (Mediterranean diet) and obesity indexes in a population of adults at high cardiovascular risk.

Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single cell tracking and traction force microscopy

Newly generated olfactory receptor axons grow from the peripheral to the central nervous system aided by olfactory ensheathing cells (OECs). Thus, OEC transplantation has emerged as a promising therapy for spinal cord injuries and for other neural diseases. However, these cells do not present a uniform population, but, instead, a functionally heterogeneous population that exhibits a variety of responses including adhesion, repulsion and crossover during cell-cell and cell-matrix interactions. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients. Here, we demonstrated that rodent OECs express all the components of the Nogo Receptor complex and that their migration is blocked by Myelin. Next, we used cell tracking and traction force microscopy to analyze OEC migration and its mechanical properties over Myelin. Our data relate the absence of traction force of OEC with lower migratory capacity, which correlates with changes in the F-Actin cytoskeleton and focal adhesion distribution. Lastly, OEC traction force and migratory capacity is enhanced after cell incubation with the Nogo Receptor inhibitor NEP1-40.

Single Heartstring aortotomy for multiple off-pump venous bypass grafts.

Off-pump coronary bypass grafting may decrease the rate of stroke, due to minimal aortic manipulation. For venous grafts, clampless hemostasis when performing the proximal anastomosis can be achieved using the Heartstring device. We describe a technique using a single device to suture two veins to one aortotomy. This technique requires less space and could be advantageous in very short, small, and calcified aortas. In to our experience, this technique is rapid, simple, easy to reproduce, and cost-saving.

A single-blind, randomised controlled trial on the effects of lithium and quetiapine monotherapy on the trajectory of cognitive functioning in first episode mania: A 12-month follow-up study.

BACKGROUND: Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania. METHODS: The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points. RESULTS: There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition. CONCLUSION: Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.

Independent and combined associations of risky single-occasion drinking and drinking volume with alcohol use disorder: Evidence from a sample of young Swiss men.

BACKGROUND: Risky single-occasion drinking (RSOD) is a prevalent and potentially harmful alcohol use pattern associated with increased alcohol use disorder (AUD). However, RSOD is commonly associated with a higher level of alcohol intake, and most studies have not controlled for drinking volume (DV). Thus, it is unclear whether the findings provide information about RSOD or DV. This study sought to investigate the independent and combined effects of RSOD and DV on AUD. METHODS: Data were collected in the longitudinal Cohort Study on Substance Use Risk Factors (C-SURF) among 5598 young Swiss male alcohol users in their early twenties. Assessment included DV, RSOD, and AUD at two time points. Generalized linear models for binomial distributions provided evidence regarding associations of DV, RSOD, and their interaction. RESULTS: DV, RSOD, and their interaction were significantly related to the number of AUD criteria. The slope of the interaction was steeper for non/rare RSOD than for frequent RSOD. CONCLUSIONS: RSOD appears to be a harmful pattern of drinking, associated with increased AUD and it moderated the relationship between DV and AUD. This study highlighted the importance of taking drinking patterns into account, for both research and public health planning, since RSO drinkers constitute a vulnerable subgroup for AUD.

Phylogenomics Controlling for Base Compositional Bias Reveals a Single Origin of Eusociality in Corbiculate Bees.

As increasingly large molecular data sets are collected for phylogenomics, the conflicting phylogenetic signal among gene trees poses challenges to resolve some difficult nodes of the Tree of Life. Among these nodes, the phylogenetic position of the honey bees (Apini) within the corbiculate bee group remains controversial, despite its considerable importance for understanding the emergence and maintenance of eusociality. Here, we show that this controversy stems in part from pervasive phylogenetic conflicts among GC-rich gene trees. GC-rich genes typically have a high nucleotidic heterogeneity among species, which can induce topological conflicts among gene trees. When retaining only the most GC-homogeneous genes or using a nonhomogeneous model of sequence evolution, our analyses reveal a monophyletic group of the three lineages with a eusocial lifestyle (honey bees, bumble bees, and stingless bees). These phylogenetic relationships strongly suggest a single origin of eusociality in the corbiculate bees, with no reversal to solitary living in this group. To accurately reconstruct other important evolutionary steps across the Tree of Life, we suggest removing GC-rich and GC-heterogeneous genes from large phylogenomic data sets. Interpreted as a consequence of genome-wide variations in recombination rates, this GC effect can affect all taxa featuring GC-biased gene conversion, which is common in eukaryotes.

Transcatheter arterial embolization for unresectable symptomatic giant hepatic hemangiomas: single-center experience using a lipiodol-ethanol mixture

AbstractObjective:The present article is aimed at reporting the author’s experience with transcatheter arterial embolization using a lipiodol-ethanol mixture in three cases of unresectable symptomatic giant hepatic hemangiomas.Materials and Methods:The cases of three patients with giant unresectable symptomatic hepatic hemangiomas embolized in the period 2009–2010 were retrospectively reviewed. In all the cases, transarterial embolization was performed with an ethanol-lipiodol mixture.Results:Symptoms regression and quality of life improvement were observed in all the cases. No complications were observed and all the patients were discharged within 12 hours after the procedure.Conclusion:Transcatheter arterial embolization using ethanol mixed with lipiodol was a safe and effective treatment for symptomatic giant hepatic hemangiomas in this small series of patients.