The Truth and Reconciliation Commission (TRC): Human Rights and State Transitions – The South Africa Model

Post-authoritarian regimes have struggled with the most appropriate way to deal with the former regimes’ human rights abuses.Several schools of though have emerged as to how this should be accomplished.Into this framework the South Africa model, the Truth and Reconciliation Commission (TRC), is discussed.The TRC has completed its charge and the results vary according to one’s perception of that charge.An assessment of South Africa’s attempt at truth and reconciliation and the TRC’s viability as a model for other transitioning societies are discussed

Morroco in Transition: Overcoming the Democratic and Human Rights Legacy of King Hassan II

Morocco’s King Hassan II died on 23 July 1999 and was succeeded by his son Muhammad VI. Much of the media coverage of Hassan II following his death portrayed him as a champion of democracy and human rights in the region. Was this really the case? Was Morocco under Hassan II becoming a more democratic and open society? This paper critically examines King Hassan’s legacy, challenges and opportunities it poses for his heir Muhammad VI. The paper also discusses Morocco’s prospects for democratic deepening under the new leader

Palliative care needs in patients hospitalized with heart failure (PCHF) study: rationale and design

Abstract Aims The primary aim of this study is to provide data to inform the design of a randomized controlled clinical trial (RCT) of a palliative care (PC) intervention in heart failure (HF). We will identify an appropriate study population with a high prevalence of PC needs defined using quantifiable measures. We will also identify which components a specific and targeted PC intervention in HF should include and attempt to define the most relevant trial outcomes. Methods An unselected, prospective, near-consecutive, cohort of patients admitted to hospital with acute decompensated HF will be enrolled over a 2-year period. All potential participants will be screened using B-type natriuretic peptide and echocardiography, and all those enrolled will be extensively characterized in terms of their HF status, comorbidity, and PC needs. Quantitative assessment of PC needs will include evaluation of general and disease-specific quality of life, mood, symptom burden, caregiver burden, and end of life care. Inpatient assessments will be performed and after discharge outpatient assessments will be carried out every 4 months for up to 2.5 years. Participants will be followed up for a minimum of 1 year for hospital admissions, and place and cause of death. Methods for identifying patients with HF with PC needs will be evaluated, and estimates of healthcare utilisation performed. Conclusion By assessing the prevalence of these needs, describing how these needs change over time, and evaluating how best PC needs can be identified, we will provide the foundation for designing an RCT of a PC intervention in HF

CCAFS Gender Strategy

This Gender Strategy is intended to strengthen CCAFS’ development impact through the integration of gender issues into research in keeping with commitments in the CGIAR Strategy and Results Framework to ensure that rural women benefit from its contribution to poverty reduction, enhanced environmental resilience, improved food security, human health and nutrition. CCAFS plans to situate its gender strategy within a broader strategy addressing social inclusion for different social groups while bearing in mind that women are central to agriculture in developing countries. This Strategy was prepared following CGIAR Guidelines for CRP Gender Strategy1 that focus on showing how the CRP will address issues of gender in its research (as distinct from gender in the workplace which will be handled separately). Accordingly, the document is organized into seven sections that together provide an explanation of how the CRP will address gender issues relevant to its research outputs, activities and outcomes and against which the CRP will report in future, as part of the CGIAR annual monitoring process

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: A phase 1 dose-escalation study

BackgroundThis phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer.MethodsPatients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2) q3w.ResultsSixty-nine patients were treated. The most common adverse events (AEs) were fatigue and nausea. Grade 3/4 AEs of special interest included neutropenia, fatigue, mucosal inflammation, anemia, thrombocytopenia, febrile neutropenia, and palmar-plantar erythrodysesthesia. The MTD was not reached. With MM-302 ≥ 30 mg/m2, overall response rate (ORR) was 13% and median progression-free survival (mPFS) 7.4 months (95% CI: 3·5-10·9) in all arms. In 25 anthracycline-naïve patients, ORR was 28·0% and mPFS 10·9 months (95% CI: 1·8-15·3). Imaging with 64Cu-labeled MM-302 visualized tumor-drug penetrance in tumors throughout the body, including the brain.ConclusionMM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m2 plus 6 mg/kg trastuzumab q3w

Camptothecin-based dendrimersomes for gene delivery and redox-responsive drug delivery to cancer cells

Combination therapy involving chemotherapeutic drugs and genes is emerging as a promising strategy to provide a synergistic therapeutic effect, to overcome drug resistance while reducing the severe side effects associated with conventional chemotherapeutic drugs. However, the lack of nanomedicines able to simultaneously carry anti-cancer drugs and nucleic acids limits the application of this therapeutic strategy. To overcome this issue, we proposed to synthesize a pro-drug dendrimer by conjugating the PEGylated, positively charged generation 3-diaminobutyric polypropylenimine dendrimer to the anti-cancer drug camptothecin with a redox-sensitive disulphide linkage, and evaluate its efficacy to co-deliver the complexed DNA and camptothecin to cancer cells. This PEGylated pro-drug dendrimer was found to spontaneously self-assemble into cationic (∼3–5 mV) vesicles at pH 7.4, at a critical aggregation concentration of about 200 μg mL−1. These vesicles (dendrimersomes) became smaller (150–200 nm) with increasing dendrimer concentration and remained stable over 7 days. They were able to release about 70% of the conjugated camptothecin in presence of 50 mM glutathione (equivalent to the intracellular environment of tumor tissue). They could also condense more than 85% of the DNA at dendrimer : DNA weight ratios of 5 : 1 and higher. DNA condensation occurred instantly and was found to be stable for at least 24 h. This led to an enhanced cellular uptake of DNA (by up to 1.6-fold) and increased gene transfection (by up to 2.4-fold) in prostate cancer cells in comparison with the unmodified dendrimer. These novel dendrimersomes are therefore promising for single carrier-based combination cancer therapy

Adherence to Accelerometer Protocols Among Women From Economically Disadvantaged Neighborhoods

Background: Objective measurement of physical activity with accelerometers is a challenging task in community-based intervention research. Challenges include distribution of and orientation to monitors, nonwear, incorrect placement, and loss of equipment. Data collection among participants from disadvantaged populations may be further hindered by factors such as transportation challenges, competing responsibilities, and cultural considerations. Methods: Research staff distributed accelerometers and provided an orientation that was tailored to the population group. General adherence strategies such as follow-up calls, daily diaries, verbal and written instructions, and incentives were accompanied by population-specific strategies such as assisting with transportation, reducing obstacles to wearing the accelerometer, tailoring the message to the participant population, and creating a nonjudgmental environment. Results: Sixty women asked to wear the Actigraph GT1M returned the accelerometer, and 57 of them provided sufficient data for analysis (at least 10 hours a day for a minimum of 4 days) resulting in 95% adherence to the protocol. Participants wore the accelerometers for an average of 5.98 days and 13.15 hours per day. Conclusions: The high accelerometer monitoring adherence among this group of economically disadvantaged women demonstrates that collection of high-quality, objective physical data from disadvantaged populations in field-based research is possible

Digital Epidemiology

Mobile, social, real-time: the ongoing revolution in the way people communicate has given rise to a new kind of epidemiology. Digital data sources, when harnessed appropriately, can provide local and timely information about disease and health dynamics in populations around the world. The rapid, unprecedented increase in the availability of relevant data from various digital sources creates considerable technical and computational challenges

The driver landscape of sporadic chordoma.

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma