Comparative assessment of the vulnerability and resilience of deltas, extended version with 14 deltas : work document

Worldwide, deltas host dense populations and are important centres of agricultural and industrial production, and economic activity. Many deltas are areas of great ecological importance as well, featuring wetlands of high and unique biodiversity. Deltas are vulnerable to changes by natural forces and human activities. Major drivers of change are population growth, economic development, climate change and subsidence

The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer

Purpose: Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab. Methods: Eligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status 64 1, no history of brain metastases, and previously received 65 1 anti-HER2 regimen for advanced disease. Patients received 160\ua0mg oral enzalutamide daily and 6\ua0mg/kg intravenous trastuzumab every 21\ua0days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24\ua0weeks (CBR24); secondary end points included progression-free survival (PFS) and safety. Results: Overall, 103\ua0women were enrolled [median age 60\ua0years (range 34\u201383)]; 62% had received 65 3\ua0lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24\ua0weeks (19%), was 24% in the efficacy evaluable set (n = 89). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4\ua0months (95% confidence interval 2.0\u20133.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade 65 3 reported in 65 3\ua0patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs. Conclusions: Enzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination. ClinicalTrials.gov number: NCT0209196

The downward spiral of mental disorders and educational attainment: a systematic review on early school leaving.

BACKGROUND: Most psychiatric disorders present symptom patterns that cause severe impairment on the emotional, cognitive and social level. Thus, adolescents who suffer from a mental disorder risk finding themselves in a downward spiral caused by the reciprocal association of psychological symptoms and negative school experiences that may culminate in early school leaving. In addition to previous collective work that mainly focused on school refusing behaviour among children and was presented as an expert's opinion, the following systematic review fills the knowledge gap by providing a structured overview of the bidirectional association between mental health and secondary school dropout based on a sound methodology and with a particular focus on mediating factors. METHODS: Four electronic databases were searched from January 1990 until June 2014. Selected references were assessed for study details, main results, mediating factors and methodological limitations. Standardized risk of bias assessment was conducted. RESULTS: Mood and anxiety disorders seemed to have a less consequential direct effect on early school leaving than substance use and disruptive behaviour disorders. The association between externalizing disorders and educational attainment was even stronger when the disorder occurred early in life. On the other hand, internalizing disorders were reported to develop as a consequence of school dropout. Only few studies had addressed gender differences, with discrepant results. Socio-economic background, academic achievement and family support were identified as significant mediating factors of the association between mental disorders and subsequent educational attainment. CONCLUSIONS: Findings suggested a strong association between mental health and education, in both directions. However, most studies focused on mediating factors that could not be targeted by intervention programs

Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes

Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients

Stakeholder enhanced environmental flow assessment: The Rufiji Basin case study in Tanzania

Environmental flows (E flows) are now a standard part of sustainable water management globally but are only rarely implemented. One reason may be insufficient engagement of stakeholders and their priority outcomes in the E flow-setting process. A recent environmental flow assessment (EFA) in the Kilombero basin of the Rufiji River in Tanzania concentrated on a broad-based investigation of stakeholders’ use and perceptions of the ecosystem services provided by the river. The EFA process generally followed the Building Block Methodology but with an enhanced engagement of stakeholders. Engagement began with the involvement of institutional stakeholders to explain the purpose of the EFA and to elicit their priority outcomes. Extensive interactions with direct-use stakeholders followed to investigate their uses of and priorities for the rivers. Results were used by the EFA specialist team in choosing flow indicators and defining measurable environmental objectives. The specialists then met to reach a consensus of the flow requirements. The EFA results were lastly reported back to stakeholders. During the Kilombero EFA we learned that stakeholders at all levels have a good awareness of the natural services provided by a healthy river and can contribute to the setting of environmental objectives for the rivers and floodplain. These can be factored into the biophysical assessments of river flows required to maintain habitats, processes, water quality and biodiversity. It is therefore important to allocate significant resources to stakeholder engagement. It now remains to be seen if enhanced stakeholder engagement, including the increased understanding and capacity built among all stakeholders, will increase support for the implementation of the recommended flows

Environmental flow case studies: Southern and Eastern Africa

SLIDES: Environmental Flow Case Studies: Southern and Eastern AfricaTanzania National Water Policy 2002 Water Resources Management Act (WRMA) No. 11 of 2009 “water for basic human needs will receive highest priority, water for the environment to protect the ecosystems that underpin our water resources will attain second priority and will be reserved” “take into account and give effect to the requirements of the reserve” Kenya Water Resources Management Rules 2007 “establish the reserve based on water resource records and reserve water demand or ecological vulnerability, human vulnerability, local observations of historic drought flows, maintenance of perennial flows and consultations with WUAs” The Water Bill 2014 "reserve, in relation to a water resource, means that quantity and quality of water required (a) to satisfy basic human needs for all people who are or may be supplied from the water resource; and (b) to protect aquatic ecosystems in order to secure ecologically sustainable development and use of the water resource

Environmental flow case studies: Southern and Eastern Africa

SLIDES: Environmental Flow Case Studies: Southern and Eastern AfricaTanzania National Water Policy 2002 Water Resources Management Act (WRMA) No. 11 of 2009 “water for basic human needs will receive highest priority, water for the environment to protect the ecosystems that underpin our water resources will attain second priority and will be reserved” “take into account and give effect to the requirements of the reserve” Kenya Water Resources Management Rules 2007 “establish the reserve based on water resource records and reserve water demand or ecological vulnerability, human vulnerability, local observations of historic drought flows, maintenance of perennial flows and consultations with WUAs” The Water Bill 2014 "reserve, in relation to a water resource, means that quantity and quality of water required (a) to satisfy basic human needs for all people who are or may be supplied from the water resource; and (b) to protect aquatic ecosystems in order to secure ecologically sustainable development and use of the water resource