Niche Construction and the Evolution of Leadership

We use the concept of niche construction - the process whereby individuals, through their activities, interactions, and choices, modify their own and each other\u27s environments - as an example of how biological evolution and cultural evolution interacted to form an integrative foundation of modern organizational leadership. Resulting adaptations are formal structures that facilitate coordination of large, postagrarian organizational networks. We provide three propositions explaining how leadership processes evolve over time within and between organizations in order to solve specific coordination problems. We highlight the balancing act between self-interests and group interests in organizations and show how leadership must regulate this tension to maintain organizational fitness. We conclude with predictions about the future evolution of leadership in organizations

Design of the e-Vita diabetes mellitus study: effects and use of an interactive online care platform in patients with type 2 diabetes (e-VitaDM-1/ZODIAC-40)

Background Due to ongoing rise in need for care for people with chronic diseases and lagging increase in number of care providers, alternative forms of care provision and self-management support are needed. Empowering patients through an online care platform could help to improve patients’ self-management and reduce the burden on the healthcare system. Methods Access to laboratory results and educational modules on diabetes will be offered through a platform for subjects with type 2 diabetes mellitus treated in primary care. Differences in socio-demographic and clinical characteristics between subjects expressing interest vs. disinterest to use the platform will be explored. Platform usage will be tracked and compared. Patient satisfaction and quality of life will be measured by validated questionnaires and economic analyses will be performed. Discussion This study is designed to assess the feasibility of use of an online platform in routine primary healthcare for subjects with type 2 diabetes mellitus in the Netherlands, and to study effects of use of the platform on treatment satisfaction, quality of life and clinical parameters. Although providing access to a online platform is not a novel intervention, usage and effects have not yet been studied in this patient population

Incidental chest radiographic findings in adult patients with acute cough

PURPOSE Imaging may produce unexpected or incidental findings with consequences for patients and ordering of future investigations. Chest radiography in patients with acute cough is among the most common reasons for imaging in primary care, but data on associated incidental findings are lacking. We set out to describe the type and prevalence of incidental chest radiography findings in primary care patients with acute cough. METHODS We report on data from a cross-sectional study in 16 European primary care networks on 3,105 patients with acute cough, all of whom were undergoing chest radiography as part of a research study workup. Apart from assessment for specified signs of pneumonia and acute bronchitis, local radiologists were asked to evaluate any additional finding on the radiographs. For the 2,823 participants with good-quality chest radiographs, these findings were categorized according to clinical relevance based on previous research evidence and analyzed for type and prevalence by network, sex, age, and smoking status. RESULTS Incidental findings were reported in 19% of all participants, and ranged from 0% to 25% by primary care network, with the network being an independent contributor (P < .001). Of all participants 3% had clinically relevant incidental findings. Suspected nodules and shadows were reported in 1.8%. Incidental findings were more common is older participants and smokers (P < .001). CONCLUSIONS Clinically relevant incidental findings on chest radiographs in primary care adult patients with acute cough are uncommon, and prevalence varies by setting

A synthetic lethal screen identifies HDAC4 as a potential target in MELK overexpressing cancers

Maternal embryonic leucine zipper kinase (MELK) is frequently overexpressed in cancer, but the role of MELK in cancer is still poorly understood. MELK was shown to have roles in many cancer-associated processes including tumor growth, chemotherapy resistance, and tumor recurrence. To determine whether the frequent overexpression of MELK can be exploited in therapy, we performed a high-throughput screen using a library of Saccharomyces cerevisiae mutants to identify genes whose functions become essential when MELK is overexpressed. We identified two such genes: LAG2 and HDA3. LAG2 encodes an inhibitor of the SCF ubiquitin-ligase complex, while HDA3 encodes a subunit of the HDA1 histone deacetylase complex. We find that one of these synthetic lethal interactions is conserved in mammalian cells, as inhibition of a human homolog of HDA3 (HDAC4) is synthetically toxic in MELK overexpression cells. Altogether, our work identified a novel potential drug target for tumors that overexpress MELK

Modeling of Cisplatin-Induced Signaling Dynamics in Triple-Negative Breast Cancer Cells Reveals Mediators of Sensitivity

Triple-negative breast cancers (TNBCs) display great diversity in cisplatin sensitivity that cannot be explained solely by cancer-associated DNA repair defects. Differential activation of the DNA damage response (DDR) to cisplatin has been proposed to underlie the observed differential sensitivity, but it has not been investigated systematically. Systems-level analysis-using quantitative time-resolved signaling data and phenotypic responses, in combination with mathematical modeling-identifies that the activation status of cell-cycle checkpoints determines cisplatin sensitivity in TNBC cell lines. Specifically, inactivation of the cell-cycle checkpoint regulator MK2 or G3BP2 sensitizes cisplatin-resistant TNBC cell lines to cisplatin. Dynamic signaling data of five cell cycle-related signals predicts cisplatin sensitivity of TNBC cell lines. We provide a time-resolved map of cisplatin-induced signaling that uncovers determinants of chemo-sensitivity, underscores the impact of cell-cycle checkpoints on cisplatin sensitivity, and offers starting points to optimize treatment efficacy

Evaluation of the New American Joint Committee on Cancer Staging Manual 8th Edition for Perihilar Cholangiocarcinoma

Background The aim was to compare the prognostic accuracy of cross-sectional imaging of the 7th and 8th editions of the American Joint Committee on Cancer(AJCC) staging system for perihilar cholangiocarcinoma(PHC). Methods All patients with PHC between 2002 and 2014 were included. Imaging at the time of presentation was reassessed and clinical tumor–node–metastasis (cTNM) stage was determined according to the 7th and 8th editions of the AJCC staging system. Comparison of the prognostic accuracy was performed using the concordance index (c-index). Results A total of 248 PHC patients were included;45 patients(18.1%) underwent a curative-intent resection, whereas 203 patients(81.9%) did not because they were unfit for surgery or were diagnosed with locally advanced or metastatic disease during workup. Prognostic accuracy was comparable between the 7th and 8th editions (c-index 0.57 vs 0.58). For patients who underwent a curative-intent resection, the prognostic accuracy of the 8t

Procjena mikrostrukture alatnog čelika za hladni rad nakon pretaljivanja pulsirajućim laserom

The aim of this study is the investigation of micro-structural behaviour of a Mat. No. 1.2379 (EN-X160CrMoV121; AISI D2) cold work tool steel after remelting with a precise pulsed Nd:YAG laser. The investigated steel is one of the most hard to weld tool steels, due to large amount of alloying elements. The analysis was done on single spots remelted with specific laser pulse shape and parameters, assuring crack-less solidification. Re-solidifi ed areas were investigated with microscopy, hardness measurements, X-ray spectroscopy and diffraction method. Laser treatment causes rapid solidification leading into a formation of a fine dendritic microstructures containing high amount of retained austenite causing a significant decrease of hardness.Namjena ove studije je ispitivanje ponašanja mikro strukture alatnoga čelika za rad na hladno Mat. No.1.2379 (ENX160CrMoV121; AISI D2) po pretaljivanju s preciznim pulsiranim Nd:YAG laserom. Zbog velike količine legirnih elemenata istraživani materijal spada u grupu vrlo teško zavarljivih alatnih čelika. Analiza je provedena na pojedinim pretaljenim točkama korištenjem specifi čnog oblika i parametara laserskog impulsa koji osiguravaju skrućivanje bez pukotina. Pretaljena područja su ispitivana mikroskopom, mjerenjem mikro tvrdoće, rendgenskom spektroskopijom i defrakcijskom metodom. Tretman laserom uzrokvao je brzo skrućivanje koja dovodi do formiranja fi ne dendritičke strukture s velikim udjelom zaostalog austenita što uzrokuje bitno smanjivanje tvrdoće

Медицинские и социальные аспекты коммерческого секса

Представлены демографические, медицинские, психологические и социальные характеристики женщин, оказывающих платные сексуальные услуги. Обсуждается проблема легализации и регламентации проституции в контексте профилактики инфекций, передающихся половым путем, и заражения ВИЧ.Demographic, medical, psychological and social characteristics of women rendering sexual services are described. The problem of legalization and regulation of prostitution in the context of prevention of sexually transmitted infections and HIV is discussed

Demographical, Clinical, and Psychological Characteristics of Users and Nonusers of an Online Platform for T2DM Patients (e-VitaDM-3/ZODIAC-44)

Background. Online platforms offer opportunities for support in changing lifestyle and taking responsibility for one&apos;s health, but engaging patients with type 2 diabetes is challenging. Previous studies have shown that patients interested in platforms were more often male, younger, and higher educated. This study aims to investigate differences in clinical and psychological characteristics between users and nonusers of a newly developed platform. Methods. A prospective study started in the Drenthe region of Netherlands. Participants in the study concerning quality of care and quality of life were additionally invited to use the platform. Results. 633 patients were registered after they opted for platform use. Of these patients, 361 (57.0%) never logged on, 184 (29.1%) were labeled &quot;curious&quot; users, and 88 (13.9%) were identified as &quot;active&quot; users. Users had lower HbA1c levels and more often hypertension compared to nonusers, and reported higher quality of life, better well-being, lower diabetes-related distress, and better medication adherence. Discussion. Platform use was associated with more favorable clinical and psychological characteristics relative to nonuse. Those with greater severity of disease, lower mood, and progression of disease used the platform the least. Other approaches need to be developed to reach these patients. Furthermore, improving the platform could also help to reach them. This trial is registered with Clinicaltrials.gov NCT01570140