Multivariable regression analysis of febrile neutropenia occurrence in early breast cancer patients receiving chemotherapy assessing patient-related, chemotherapy-related and genetic risk factors.

BACKGROUND: Febrile neutropenia (FN) is common in breast cancer patients undergoing chemotherapy. Risk factors for FN have been reported, but risk models that include genetic variability have yet to be described. This study aimed to evaluate the predictive value of patient-related, chemotherapy-related, and genetic risk factors. METHODS: Data from consecutive breast cancer patients receiving chemotherapy with 4-6 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) or three cycles of FEC and docetaxel were retrospectively recorded. Multivariable logistic regression was carried out to assess risk of FN during FEC chemotherapy cycles. RESULTS: Overall, 166 (16.7%) out of 994 patients developed FN. Significant risk factors for FN in any cycle and the first cycle were lower platelet count (OR = 0.78 [0.65; 0.93]) and haemoglobin (OR = 0.81 [0.67; 0.98]) and homozygous carriers of the rs4148350 variant T-allele (OR = 6.7 [1.04; 43.17]) in MRP1. Other significant factors for FN in any cycle were higher alanine aminotransferase (OR = 1.02 [1.01; 1.03]), carriers of the rs246221 variant C-allele (OR = 2.0 [1.03; 3.86]) in MRP1 and the rs351855 variant C-allele (OR = 2.48 [1.13; 5.44]) in FGFR4. Lower height (OR = 0.62 [0.41; 0.92]) increased risk of FN in the first cycle. CONCLUSIONS: Both established clinical risk factors and genetic factors predicted FN in breast cancer patients. Prediction was improved by adding genetic information but overall remained limited. Internal validity was satisfactory. Further independent validation is required to confirm these findings

Dehydroepiandrosterone sulfate mediates activation of transcription factors CREB and ATF-1 via a Gα11-coupled receptor in the spermatogenic cell line GC-2

AbstractDehydroepiandrosterone sulfate (DHEAS) is a circulating steroid produced in the adrenal cortex, brain, and gonads. Whereas a series of investigations attest to neuroprotective effects of the steroid in the brain, surprisingly little is known about the physiological effects of DHEAS on cells of the reproductive system. Here we demonstrate that DHEAS acting on the spermatogenic cell line GC-2 induces a time- and concentration-dependent phosphorylation of c-Src and Erk1/2 and activates the transcription factors activating transforming factor-1 (ATF-1) and cyclic AMP-responsive element binding protein (CREB). These actions are consistent with the non-classical signaling pathway of testosterone and suggest that DHEAS is a pro-androgen that is converted into testosterone in order to exert its biological activity. The fact, however, that steroid sulfatase mRNA was not detected in the GC-2 cells and the clear demonstration of DHEAS-induced activation of Erk1/2, ATF-1 and CREB after silencing the androgen receptor by small interfering RNA (siRNA) clearly contradict this assumption and make it appear unlikely that DHEAS has to be converted in the cytosol into a different steroid in order to activate the kinases and transcription factors mentioned. Instead, it is likely that the DHEAS-induced signaling is mediated through the interaction of the steroid with a membrane-bound G-protein-coupled receptor, since silencing of Guanine nucleotide-binding protein subunit alpha-11 (Gnα11) leads to the abolition of the DHEAS-induced stimulation of Erk1/2, ATF-1, and CREB. The investigation presented here shows a hormone-like activity of DHEAS on a spermatogenic cell line. Since DHEAS is produced in male and female reproductive organs, these findings could help to define new roles for DHEAS in the physiology of reproduction

Simulation modeling for stratified breast cancer screening : a systematic review of cost and quality of life assumptions

BACKGROUND: The economic evaluation of stratified breast cancer screening gains momentum, but produces also very diverse results. Systematic reviews so far focused on modeling techniques and epidemiologic assumptions. However, cost and utility parameters received only little attention. This systematic review assesses simulation models for stratified breast cancer screening based on their cost and utility parameters in each phase of breast cancer screening and care. METHODS: A literature review was conducted to compare economic evaluations with simulation models of personalized breast cancer screening. Study quality was assessed using reporting guidelines. Cost and utility inputs were extracted, standardized and structured using a care delivery framework. Studies were then clustered according to their study aim and parameters were compared within the clusters. RESULTS: Eighteen studies were identified within three study clusters. Reporting quality was very diverse in all three clusters. Only two studies in cluster 1, four studies in cluster 2 and one study in cluster 3 scored high in the quality appraisal. In addition to the quality appraisal, this review assessed if the simulation models were consistent in integrating all relevant phases of care, if utility parameters were consistent and methodological sound and if cost were compatible and consistent in the actual parameters used for screening, diagnostic work up and treatment. Of 18 studies, only three studies did not show signs of potential bias. CONCLUSION: This systematic review shows that a closer look into the cost and utility parameter can help to identify potential bias. Future simulation models should focus on integrating all relevant phases of care, using methodologically sound utility parameters and avoiding inconsistent cost parameters

A multi-level spectral deferred correction method

The spectral deferred correction (SDC) method is an iterative scheme for computing a higher-order collocation solution to an ODE by performing a series of correction sweeps using a low-order timestepping method. This paper examines a variation of SDC for the temporal integration of PDEs called multi-level spectral deferred corrections (MLSDC), where sweeps are performed on a hierarchy of levels and an FAS correction term, as in nonlinear multigrid methods, couples solutions on different levels. Three different strategies to reduce the computational cost of correction sweeps on the coarser levels are examined: reducing the degrees of freedom, reducing the order of the spatial discretization, and reducing the accuracy when solving linear systems arising in implicit temporal integration. Several numerical examples demonstrate the effect of multi-level coarsening on the convergence and cost of SDC integration. In particular, MLSDC can provide significant savings in compute time compared to SDC for a three-dimensional problem

UPAYA MENINGKATKAN MOTIVASI BELAJAR SISWA MELALUI MEDIA GAME EDUCATION DALAM PEMBELAJARAN IPS DI MTs HASBUR RACHMAN ALIF DESA LENGKONG WETAN KABUPATEN MAJALENGKA

ASEP SAMSUL MA'ARIF : Berdasarkan Observasiawal di kelas VII MTs Hasbur Rachman Alif terlihat proses pembelajaran IPS masih menggunakan media spidol dan papan tulis. Sehingga banyak siswa yang kurang memperhatikan guru pada saat proses pembelajaran., Hal ini berakibat pada kejenuhan dan kebosanan yang berdampak pada hasil belajar siswa yang kurang dari KKM yang diterapkan di MTs Hasbur Rachman Alif yakni 70. Tujuan penelitian ini untuk mengetahui bagaimana penerapan pembelajaran dengan menggunakan media Game Education pada mata pelajaran IPS Terpadu, aktivitas siswa dan kinerja guru dengan pembelajaran dengan menggunakan media Game Education, dan mengetahui motivasi belajar siswa sebelum dan setelah diterapkannya pembelajaran dengan menggunakan media Game education pada mata pelajaran IPS Terpadu di MTs Hasbur Rachman Alif. Pembelajaran dengan menggunakan media Game Education menekankan motivasi siswa untuk berpikir kritis dan menuangkan. Hal ini memudahkan siswa untuk mengakses materi IPS yang banyak dimanapun, serta mempemudah daya ingat siswa tentang apayatgtelah didapatkan selama proses pembelajaran. Penelitian ini menggunakan Penelitian Tindakan Kelas (pTK) yang dilaksanakan selama tiga siklus. Teknik Pengumpulan data menggunakan observasi, tes, dan dokumentasi. Subjek penelitian ini adalah siswa kelas VII MTs Hasbur Rachman Alif sebanyak 31 siswa yang terdiri dari 18 siswa laki-laki dan 13 siswa perempuan. Pembelajaran dengan menggunakan media Game Education dapat meningkatkan motivasi belajar siswa hal ini terlihat dari hasil tes yang telah dilakukan selama tiga siklus, dimana pada pratindakan (pretes) nilai sebesar 65,25 dan ketuntasan belajar 25 yo, siklus I nilai rata-rata sebesar 76,75 dan ketuntasan_ belajar siswa sebesar 65,5%o siklus II nilai rata-rata siswa 85,75 dan nilai ketuntasan belajar sebesar 90% siklus III dengan nilai rata-rata 92,25 dan ketuntasan belajar mengalami peningkatanya itu 97,5yo. Dengan demikian dapat disimpulkan bahwa pembelajaran dengan menggunakan media Game Education merupakan salah satu upaya untuk meningkatkan hasil belajar siswa pada mata pelajaran IPS Terpadu di MTs Hasbur Rachman Alif. Kata Kunci: Game Education, MotivasiBelajar, PTK

The Behavior, onḂ0,11, of an Oscillatory Integral with Polynomial Phase Function

AbstractWe study the convolution oscillatory singular integral operatorTf=p.v.Ω∗f, with Ω(x)=eiq(x)K(x), whereqis a real-valued polynomial of a real variable, of degreed≥2, andKis a Calderón–Zygmund-type kernel. We prove that this operator extends to an operator that maps the Besov spaceḂ0,11into the Hardy-type spaceH10

Prevalence, symptoms and management of uterine fibroids: an international internet-based survey of 21,746 women

<p>Abstract</p> <p>Background</p> <p>In 2009 the Uterine Bleeding and Pain Women's Research Study (UBP-WRS) was conducted interviewing 21,479 women across 8 countries in order to gain patient-based prevalence data on uterine pain and bleeding indications and investigate uterine symptoms and women's treatment experiences. This article shows relevant results of the study for the indication uterine fibroids providing data on self-reported prevalence, symptomatology and management of uterine fibroids.</p> <p>Methods</p> <p>2,500 women (USA: 4,500 women) in each country (Brazil, Canada, France, Germany, Italy, South Korea, the UK, the USA) completed an online survey. Women included were in their reproductive age (age group 15-49 years; USA: 18-49 years) and had ever experienced menstrual bleedings. Quotas were applied for age, region, level of education and household income of respondents. Variables have been analyzed descriptively and exploratory statistical tests have been performed.</p> <p>Results</p> <p>The self-reported prevalence of uterine fibroids ranged from 4.5% (UK) to 9.8% (Italy), reaching 9.4% (UK) to 17.8% (Italy) in the age group of 40-49 years. Women with a diagnosis of uterine fibroids reported significantly more often about bleeding symptoms than women without a diagnosis: heavy bleedings (59.8% vs. 37.4%), prolonged bleedings (37.3% vs. 15.6%), bleeding between periods (33.3% vs. 13.5%), frequent periods (28.4% vs. 15.2%), irregular and predictable periods (36.3% vs. 23.9%). Furthermore women with diagnosed uterine fibroids reported significantly more often about the following pain symptoms: pressure on the bladder (32.6% vs. 15.0%), chronic pelvic pain (14.5% vs. 2.9%), painful sexual intercourse (23.5% vs. 9.1%) and pain occurring mid-cycle, after and during menstrual bleeding (31.3%, 16.7%, 59.7%, vs. 17.1%, 6.4%, 52.0%). 53.7% of women reported that their symptoms had a negative impact on their life in the last 12 month, influencing their sexual life (42.9%), performance at work (27.7%) and relationship & family (27.2%).</p> <p>Conclusions</p> <p>Uterine fibroid is a common concern in women at fertile age causing multiple bleeding and pain symptoms which can have a negative impact on different aspects in women's life.</p

Time-Action Analysis (TAA) of the Surgical Technique Implanting the Collum Femoris Preserving (CFP) Hip Arthroplasty. TAASTIC trial Identifying pitfalls during the learning curve of surgeons participating in a subsequent randomized controlled trial (An observational study)

<p>Abstract</p> <p>Background</p> <p>Two types of methods are used to assess learning curves: outcome assessment and process assessment. Outcome measures are usually dichotomous rare events like complication rates and survival or require an extensive follow-up and are therefore often inadequate to monitor individual learning curves. Time-action analysis (TAA) is a tool to objectively determine the level of efficiency of individual steps of a surgical procedure.</p> <p>Methods/Design</p> <p>We are currently using TAA to determine the number of cases needed for surgeons to reach proficiency with a new innovative hip implant prior to initiating a multicentre RCT. By analysing the unedited video recordings of the first 20 procedures of each surgeon the number and duration of the actions needed for a surgeon to achieve his goal and the efficiency of these actions is measured. We constructed a taxonomy or list of actions which together describe the complete surgical procedure. In the taxonomy we categorised the procedure in 5 different Goal Oriented Phases (GOP):</p> <p>1. the incision phase</p> <p>2. the femoral phase</p> <p>3. the acetabulum phase</p> <p>4. the stem phase</p> <p>5. the closure pase</p> <p>Each GOP was subdivided in Goal Oriented Actions (GOA) and each GOA is subdivided in Separate Actions (SA) thereby defining all the necessary actions to complete the procedure. We grouped the SAs into GOAs since it would not be feasible to measure each SA. Using the video recordings, the duration of each GOA was recorded as well as the amount of delay. Delay consists of repetitions, waiting and additional actions. The nett GOA time is the total GOA time – delay and is a representation of the level of difficulty of each procedure. Efficiency is the percentage of nett GOA time during each procedure.</p> <p>Discussion</p> <p>This allows the construction of individual learning curves, assessment of the final skill level for each surgeon and comparison of different surgeons prior to participation in an RCT. We believe an objective and comparable assessment of skill level by process assessment can improve the value of a surgical RCT in situations where a learning curve is expected.</p