An outline of a National Health Education programme

No Abstract

TALEN-mediated apc mutation in Xenopus tropicalis phenocopies familial adenomatous polyposis

Truncating mutations in the tumor suppressor gene adenomatous polyposis coli (APC) are the initiating step in the vast majority of sporadic colorectal cancers, and they underlie familial adenomatous polyposis (FAP) syndromes. Modeling of APC- driven tumor formation in the mouse has contributed substantially to our mechanistic understanding of the associated disease, but additional models are needed to explore therapeutic opportunities and overcome current limitations of mouse models. We report on a novel and penetrant genetic cancer model in Xenopus tropicalis, an aquatic tetrapod vertebrate with external development, diploid genome and short life cycle. Tadpoles and froglets derived from embryos injected with TAL effector nucleases targeting the apc gene rapidly developed intestinal hyperplasia and other neoplasms observed in FAP patients, including desmoid tumors and medulloblastomas. Bi-allelic apc mutations causing frame shifts were detected in the tumors, which displayed activation of the Wnt/β-catenin pathway and showed increased cellular proliferation. We further demonstrate that simultaneous double bi-allelic mutation of apc and a non-relevant gene is possible in the neoplasias, opening the door for identification and characterization of effector or modifier genes in tumors expressing truncated apc. Our results demonstrate the power of modeling human cancer in Xenopus tropicalis using mosaic TALEN-mediated bi-allelic gene disruption

Performance management in practice : a study of the public sector and a specific educational facility

Thesis (MPA)--Stellenbosch University, 2002.ENGLISH ABSTRACT: Performance management is an activity of the greatest of importance in any organization, whether that organisation functions within the public or private sector. The importance of performance management has however grown greatly within the public sector due to a renewed focus on efficiency, effectiveness and economy of actions. Within an environment increasingly characterised by a scarcity of resources, the application of performance management has therefore become an essential component. This applied research study hence examines the role of performance management within the public sector. The importance of this essay is due to the fact that very limited research has been done in this field in So~th Africa concerning the modification and application of performance management, which was primarily a private sector initiative, on the more complex public sector. By making use of historical and descriptive research methods, the researcher furthermore analyses the usage of performance management within a particular educational facility. This research study therefore focuses on the formulation and implementation of a performance management instrument for the measurement of the performance of administrative and support personnel employed by the specific educational facility, with the objective to solve existing performance problems within the organisation.AFRIKAANSE OPSOMMING: Prestasiebestuur is 'n aktiwiteit wat van allergrootste belang is in enige organisasie, hetsy die organisasie in die private sektor of die openbare sektor funksioneer. Die belangrike rol van prestasiebestuur binne die openbare sektor het egter aansienlik gegroei met die openbare sektor se hernude fokus op effektiwiteit, doeltreffendheid en ekonomie van aktiwiteite. Binne 'n omgewing wat toenemend gekenmerk word deur 'n skaarsheid van hulpbronne, word die toepassing van prestasiebestuur gevolglik 'n ononbeerlike komponent. Vervolgens bestudeer hierdie toegepaste meestersvlak navorsingstuk die rol van prestasiebestuur binne die openbare sektor. Die uiterste belangrikheid van hierdie navorsingstuk spruit uit die beperkte hoeveelheid navorsing wat daar binne hierdie veld gedoen is rakende die aanpassing en toepassing van prestasiebestuur, wat aanvanklik slegs binne die privaat sektor gebruik is, op die meer komplekse openbare sektor. Verder ondersoek die navorser deur middel van historiese en beskrywende navorsingsmetodes ook die gebruik van prestasiebestuur binne 'n spesifieke onderwysinstelling. Die werkstuk fokus gevolglik op die formulering en implementering van 'n prestasie metingsinstrument vir die meting van die prestasie van administratiewe en ondersteuningspersoneel verbonde aan die spesifieke onderwysinstelling, met die oog daarop om bestaande prestasie probleme binne die organisasie op te los

CRISPR/Cas9 mediated knockout of rb1 and rbl1 leads to rapid and penetrant retinoblastoma development in Xenopus tropicalis

Retinoblastoma is a pediatric eye tumor in which bi-allelic inactivation of the Retinoblastoma 1 (RB1) gene is the initiating genetic lesion. Although recently curative rates of retinoblastoma have increased, there are at this time no molecular targeted therapies available. This is, in part, due to the lack of highly penetrant and rapid retinoblastoma animal models that facilitate rapid identification of targets that allow therapeutic intervention. Different mouse models are available, all based on genetic deactivation of both Rb1 and Retinoblastoma-like 1 (Rbl1), and each showing different kinetics of retinoblastoma development. Here, we show by CRISPR/Cas9 techniques that similar to the mouse, neither rb1 nor rbl1 single mosaic mutant Xenopus tropicalis develop tumors, whereas rb1/rbl1 double mosaic mutant tadpoles rapidly develop retinoblastoma. Moreover, occasionally presence of pinealoblastoma (trilateral retinoblastoma) was detected. We thus present the first CRISPR/Cas9 mediated cancer model in Xenopus tropicalis and the first genuine genetic non-mammalian retinoblastoma model. The rapid kinetics of our model paves the way for use as a pre-clinical model. Additionally, this retinoblastoma model provides unique possibilities for fast elucidation of novel drug targets by triple multiplex CRISPR/Cas9 gRNA injections (rb1 + rbl1 + modifier gene) in order to address the clinically unmet need of targeted retinoblastoma therapy

Process Development of Silicon Heterojunction Interdigitated Back-Contacted (SHJ-IBC) Solar Cells Bonded to Glass

In imec’s i2-module concept, silicon heterojunction interdigitated back-contacted (SHJ-IBC) solar cells are fabricated on monocrystalline foils bonded to glass. The proposed technology allows for cell processing on thin wafers mechanically supported by the glass, increasing the yield of processing such thin wafers. A process sequence for SHJ-IBC cell fabrication that can be applied to bonded thin foils is described. We investigated and optimized individual process steps on thick wafers. Then the developed steps were integrated into a process flow to fabricate solar cells on wafers with different thicknesses and bonding agents. On wafers with a thickness of 190 μm, functional cells with efficiencies of 22.6% and 21.7% were made on freestanding and silicone bonded wafers, respectively. On thin wafers of 57 μm, our best SHJ-IBC cell on an EVA bonded wafer exhibits excellent Voc of 740 mV and efficiency of 20.0%, which demonstrates the high potential of the i2-module concept

The impact of dental restorations' quality on caries risk

publishersversionPeer reviewe

A phase II, multicenter, open-label study of abemaciclib and letrozole in patients with estrogen receptor-positive rare ovarian cancer: ALEPRO trial

Background Low-grade serous and endometrioid ovarian cancers and adult-type granulosa cell tumors are rare ovarian malignancies that show high estrogen receptor positivity. Recurrences of these subtypes of ovarian cancer are often treated with conventional chemotherapy, although response rates are disappointing. Primary Objective To determine the overall response rate of the combination therapy of abemaciclib and letrozole in patients with estrogen receptor-positive rare ovarian cancers. Study Hypothesis The combination therapy of abemaciclib and letrozole will provide a clinically meaningful therapeutic benefit, with an overall response rate of >25%. Trial Design This is a phase II, international, multicenter, open-label, single-arm study to evaluate the efficacy and safety of abemaciclib and letrozole in patients with advanced, recurrent, and/or metastatic estrogen receptor-positive, rare ovarian cancer. The study will follow a tandem two-stage design. Major Inclusion/Exclusion Criteria Patients must have histologically confirmed low-grade serous/ endometrioid ovarian cancer or adult-type granulosa cell tumor with estrogen receptor positivity on immunohistochemistry. Patients need to have recurrent and measurable disease according to Radiologic Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A maximum of two prior lines of endocrine therapy are allowed, and patients cannot have previously received a cyclin-dependent kinase inhibitor. Patients with platinum-refractory disease are not allowed in any stage of the study. Primary Endpoint Investigator-assessed confirmed overall response rate, defined as the proportion of patients with a complete or partial response according to RECIST v1.1. Sample Size 40 to 100 patients will be included, depending on the results of the interim analysis. Patients will be included in Belgium, France and the Netherlands. Estimated Dates for Completing Accrual and Presenting Results Patient recruitment will be completed by the end of 2025 and reporting of the final study results will be done by the end of 2027

Robot-assisted surgery for women with endometrial cancer: Surgical and oncologic outcomes within a Belgium gynaecological oncology group cohort.

peer reviewed[en] OBJECTIVE: To evaluate surgical and oncologic outcomes of patients treated by robot-assisted surgery for endometrial cancer within the Belgium Gynaecological Oncology Group (BGOG). STUDY DESIGN: We performed a retrospective analysis of women with clinically Stage I endometrial cancer who underwent surgical treatment from 2007 to 2018 in five institutions of the BGOG group. RESULTS: A total of 598 consecutive women were identified. The rate of conversion to laparotomy was low (0.8%). The mean postoperative Complication Common Comprehensive Index (CCI) score was 3.4. The rate of perioperative complications did not differ between age groups, however the disease-free survival was significantly lower in patients over 75 years compared to patients under 65 years of age (p=0.008). Per-operative complications, conversion to laparotomy rate, post-operative hospital stay, CCI score and disease-free survival were not impacted by increasing BMI. CONCLUSION: Robot-assisted surgery for the surgical treatment of patients suffering from early-stage endometrial cancer is associated with favourable surgical and oncologic outcomes, particularly for unfavourable groups such as elderly and obese women, thus permitting a low morbidity minimally-invasive surgical approach for the majority of patients in expert centres

preoperative c reactive protein and thrombocyte count as potential markers for longterm survival in ovarian cancer

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Real-life data on treatment and outcomes in advanced ovarian cancer : An observational, multinational cohort study (RESPONSE trial)

Background This study aimed to describe the treatment strategies and outcomes for women with newly diagnosed advanced high-grade serous or endometrioid ovarian cancer (OC). Methods This observational study collected real-world medical record data from eight Western countries on the diagnostic workup, clinical outcomes, and treatment of adult women with newly diagnosed advanced (Stage III-IV) high-grade serous or endometrioid OC. Patients were selected backward in time from April 1, 2018 (the index date), with a target of 120 patients set per country, followed for >= 20 months. Results Of the 1119 women included, 66.9% had Stage III disease, 11.7% had a deleterious BRCA mutation, and 26.6% received bevacizumab; 40.8% and 39.3% underwent primary debulking surgery (PDS) and interval debulking surgery (IDS), respectively. Of the patients who underwent PDS, 55.5% had no visible residual disease (VRD); 63.9% of the IDS patients had no VRD. According to physician-assessed responses (at the first assessment after diagnosis and treatment), 53.2% of the total population had a complete response and 25.7% had a partial response to first-line chemotherapy after surgery. After >= 20 months of follow-up, 32.9% of the patients were disease-free, 46.4% had progressive disease, and 20.6% had died. Bevacizumab use had a significant positive effect on overall survival (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91; p = .01). A deleterious BRCA status had a significant positive effect on progression-free survival (HR, 0.60; 95% CI, 0.41-0.84; p < .01). Conclusions Women with advanced high-grade serous or endometrioid OC have a poor prognosis. Bevacizumab use and a deleterious BRCA status were found to improve survival in this real-world population. Lay summary Patients with advanced (Stage III or IV) ovarian cancer (OC) have a poor prognosis. The standard treatment options of surgery and chemotherapy extend life beyond diagnosis for 5 years or more in only approximately 45% of patients. This study was aimed at describing the standard of care in eight Western countries and estimating how many patients who are diagnosed with high-grade serous or endometrioid OC could potentially be eligible for first-line poly(adenosine diphosphate ribose) polymerase inhibitor (PARPi) maintenance therapy. The results highlight the poor prognosis for these patients and suggest that a significant proportion (79%) would potentially be eligible for first-line PARPi maintenance treatment.Peer reviewe