Zielführende Konzepte oder Modeerscheinungen?

Auf Grund der stetig ansteigenden Ansprüche der Kunden, in Bezug auf Qualität, Kosten und der raschen Erfüllung von Bedürfnissen, müssen Unternehmen große Anstrengungen auf sich nehmen, damit sie konkurrenzfähig bleiben. Deshalb erlebten Qualitätsmanagement-Methoden in den letzten Jahren einen „Boom“. In dieser Arbeit soll nun untersucht werden, welche Qualitätsmanagement-Methode die größte Kostenersparnis im Hinblick auf die Beschaffungsstrategie mit sich bringt, unter der Annahme, dass die Steigerung der Qualität erfolgreich ist. Zu Beginn werden die Methoden (JIT, Kanban, Poka Yoke, Six Sigma) vorgestellt und die Ziele, deren Nutzen, sowie die wesentlichen Punkte der Implementierung und Probleme, die bei der Nutzung entstehen können, erläutert. Im Anschluss werden die Methoden mit dem Economic Order Quantity Modell verglichen, um festzustellen, welches System die größte Kostenersparnis bietet. Dabei wird angenommen, dass das Unternehmen die Qualität erfolgreich verbessern konnte, und somit die Kosten der Lagerhaltung, der fehlerhaften Teile und jene für schlechte Qualität als Vergleichskriterien herangezogen werden. Daraufhin werden die Berechnungen anhand von Zahlenbeispielen veranschaulicht und untersucht, wie sich die Veränderung einzelner Parameter auf den Kostenvorteil auswirkt. Der Vergleich der unterschiedlichen Methoden zeigt, dass Just in Time den größten Kostenvorteil bietet, und dass die Wahrscheinlichkeit von fehlerhaften Teilen den größten Einfluss auf den Kostenvorteil hat. Der Kostenvorteil sinkt je geringer die Wahrscheinlichkeit von Fehlern ist. Abschließend wird noch ein Ausblick auf Möglichkeiten zur Erweiterung der beschriebenen Modelle gegeben.Due to the continual increasing demand of customers, concerning quality, costs and the fulfillment of requirements, businesses have to undertake great efforts for remaining competitive. Therefore quality management methods experienced a real “boom” in the past few years. The purpose of this diploma thesis is now to investigate which quality management method leads to the biggest cost savings under the assumption, that the aim of improving quality is successful. At the outset the methods (JIT, Kanban, Poka Yoke, and Six Sigma) are introduced and their aims, benefits and the most important steps of the implementation as well as problems, which can occur through the usage of the methods, are explained. Subsequently the methods are compared to the Economic Order Quantity model for determining the method that offers the largest cost savings under the assumption that the company is successful in improving quality thus the holding costs, costs for defective parts and those for poor quality are approached as criteria for comparison. Then the calculations are being presented in numerical examples and examined on how the modification of parameters affects cost advantages. The comparison of the different methods shows, that JIT offers the largest cost advantages and that the probability of defective parts has the strongest influence on the cost advantage. The smaller the probability is the lower are the cost advantages. Concluding there are given possibilities to expand the models described above

Psychotherapy in Jordan: An Investigation of the Host and Syrian Refugee Community's Perspectives

Little is known about patient satisfaction, bias, stigma, and the effects of psychotherapy within the Kingdom of Jordan or the Arab world in general. The purpose of this study was to explore the perceptions of both the Jordanian host and refugee community members from the psychotherapeutic services offered at various mental health care settings in Jordan. A sample of 100 patients who received psychosocial expert interventions was recruited between October and December 2017 in Amman, Jordan. Participants were either from the host or Syrian refugee community or contacted through multiple organizations working in the mental health field. The Patient Satisfaction Questionnaire, which consists of four subscales covering 1) patient satisfaction, 2) bias toward therapy, 3) effects of therapy, and 4) stigma, was administered. As a means of investigation and exploration, descriptive statistics of participant responses are displayed. Results revealed overall high rates of satisfaction with provided services and perceived benefits of psychotherapeutic interventions. However, respondents showed ambivalence regarding bias and stigma. Subsample analyses indicated no significant differences between both communities. These findings give an understanding of perceptions surrounding psychotherapy in Jordan and some insights on therapeutic processes that may be useful for clinical applications and future research

A Survey of Georgia Adult Protective Service Staff: Implications for Older Adult Injury Prevention and Policy

Background: The aging population is a rapidly growing demographic. Isolation and limited autonomy render many of the elderly vulnerable to abuse, neglect and exploitation. As the population grows, so does the need for Adult Protective Services (APS). This study was conducted to examine current knowledge of older adult protection laws in Georgia among APS staff and to identify training opportunities to better prepare the APS workforce in case detection and intervention. Methods: The Georgia State University Institute of Public Health faculty developed a primary survey in partnership with the Georgia Division of Aging Services\u27 leadership to identify key training priority issues for APS caseworkers and investigators. A 47-item electronic questionnaire was delivered to all APS employees via work-issued email accounts. We conducted descriptive analyses, t-tests and chi-square analyses to determine APS employees’ baseline knowledge of Georgia’s elder abuse policies, laws and practices, as well as examine associations of age, ethnicity, and educational attainment with knowledge. We used a p-value of 0.05 and 95% confidence intervals to determine statistical significance of analyses performed. Result: Ninety-two out of 175 APS staff responded to the survey (53% response rate). The majority of respondents were Caucasian (56%) women (92%). For over half the survey items, paired sample t-tests revealed significant differences between what APS staff reported as known and what APS staff members indicated they needed to know more about in terms of elder abuse and current policies. Chi-square tests revealed that non-Caucasians significantly preferred video conferencing as a training format (44% compared to 18%), [χ2(1) = 7.102, p \u3c .008], whereas Caucasians preferred asynchronous online learning formats (55% compared to 28%) [χ2(1) =5.951, p \u3c .015]. Conclusion: Results from this study provide the Georgia Division of Aging with insight into specific policy areas that are not well understood by APS staff. Soliciting input from intended trainees allows public health educators to tailor and improve training sessions. Trainee input may result in optimization of policy implementation, which may result in greater injury prevention and protection of older adults vulnerable to abuse, neglect and exploitation

Fungal entomopathogens: new insights on their ecology

An important mechanism for insect pest control should be the use of fungal entomopathogens. Even though these organisms have been studied for more than 100 y, their effective use in the field remains elusive. Recently, however, it has been discovered that many of these entomopathogenic fungi play additional roles in nature. They are endophytes, antagonists of plant pathogens, associates with the rhizosphere, and possibly even plant growth promoting agents. These findings indicate that the ecological role of these fungi in the environment is not fully understood and limits our ability to employ them successfully for pest management. In this paper, we review the recently discovered roles played by many entomopathogenic fungi and propose new research strategies focused on alternate uses for these fungi. It seems likely that these agents can be used in multiple roles in protecting plants from pests and diseases and at the same time promoting plant growth

Identification of Functional Networks of Estrogen- and c-Myc-Responsive Genes and Their Relationship to Response to Tamoxifen Therapy in Breast Cancer

BACKGROUND: Estrogen is a pivotal regulator of cell proliferation in the normal breast and breast cancer. Endocrine therapies targeting the estrogen receptor are effective in breast cancer, but their success is limited by intrinsic and acquired resistance. METHODOLOGY/PRINCIPAL FINDINGS: With the goal of gaining mechanistic insights into estrogen action and endocrine resistance, we classified estrogen-regulated genes by function, and determined the relationship between functionally-related genesets and the response to tamoxifen in breast cancer patients. Estrogen-responsive genes were identified by transcript profiling of MCF-7 breast cancer cells. Pathway analysis based on functional annotation of these estrogen-regulated genes identified gene signatures with known or predicted roles in cell cycle control, cell growth (i.e. ribosome biogenesis and protein synthesis), cell death/survival signaling and transcriptional regulation. Since inducible expression of c-Myc in antiestrogen-arrested cells can recapitulate many of the effects of estrogen on molecular endpoints related to cell cycle progression, the estrogen-regulated genes that were also targets of c-Myc were identified using cells inducibly expressing c-Myc. Selected genes classified as estrogen and c-Myc targets displayed similar levels of regulation by estrogen and c-Myc and were not estrogen-regulated in the presence of siMyc. Genes regulated by c-Myc accounted for 50% of all acutely estrogen-regulated genes but comprised 85% (110/129 genes) in the cell growth signature. siRNA-mediated inhibition of c-Myc induction impaired estrogen regulation of ribosome biogenesis and protein synthesis, consistent with the prediction that estrogen regulates cell growth principally via c-Myc. The 'cell cycle', 'cell growth' and 'cell death' gene signatures each identified patients with an attenuated response in a cohort of 246 tamoxifen-treated patients. In multivariate analysis the cell death signature was predictive independent of the cell cycle and cell growth signatures. CONCLUSIONS/SIGNIFICANCE: These functionally-based gene signatures can stratify patients treated with tamoxifen into groups with differing outcome, and potentially identify distinct mechanisms of tamoxifen resistance

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead