A socio-ecological survey in Inhambane Bay mangrove ecosystems : biodiversity, livelihoods, and conservation

Mangroves are highly productive ecosystems that provide a variety of ecosystem services to local communities. Mangrove ecosystems are important blue carbon ecosystems that support unique fauna, flora, and livelihoods. The decline and degradation of mangrove populations, mostly due to anthropogenic impacts and climate change, necessitate protection worldwide. There is limited research on the conservation and management of these ecosystems in Mozambique. A combination of six biodiversity surveys, thirty-one semi-structured interviews and participant observation at six sites was used to describe and understand mangrove ecosystems in Inhambane Bay. This study is among the first to involve local community leaders as academic co-authors, thus highlighting the value of local ecological knowledge and community involvement, both of which are necessary for a comprehensive understanding of mangrove ecosystems. Social and ecological approaches were integrated to describe mangrove ecosystems, perceived ecosystem services and benefits to local communities. This study has identified areas of increased mangrove cover and areas with disturbance. Out of the seven mangrove species that occur in Inhambane Bay, Avicennia marina was the most abundant mangrove species in at least three sites, and Xylocarpus granatum the least abundant mangrove species, present only in two sites. Perceived benefits include provisioning, supporting and regulating services. Community initiatives to protect mangroves include enforcing environmental laws, prohibiting cutting mangrove trees, and replanting. This study shows that community initiatives for law enforcement and mangrove restoration play an important role in raising awareness and actively protecting mangroves

Long-term follow-up of IPEX syndrome patients after different therapeutic strategies : an international multicenter retrospective study

Background: Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n 5 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. Conclusions: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term.disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen

The contribution of tourism to coastal livelihoods in Ponta do Ouro, Southern Mozambique

Tourism is increasingly seen as a panacea for the problems of rural areas, especially in developing countries. It is promoted by governments and international development organizations as a vehicle for achieving development, poverty reduction and economic growth. However, tourism has resulted in many unwanted economic, social, cultural and environmental consequences for local communities. Through a case study conducted in Ponta do Ouro, Southern Mozambique, this research sought to investigate the contribution of tourism to coastal livelihoods. The research assessed the extent to which tourism contributes to livelihoods of coastal communities of Ponta do Ouro, and their perception of benefits and negative impacts associated with tourism. Qualitative methods were used to collect data and included five focus group meetings, 46 key informant interviews, and participant observation. Findings of this study reveal that despite providing employment and other economic benefits to the livelihoods of the community of Ponta do Ouro, tourism also resulted in negative impacts on community livelihoods. These included overcrowding during high tourism seasons, loss of access to public land, rising prices of properties, goods and services, and an increase in crime, alcohol use and pollution. Therefore a pro-poor tourism approach is recommended as an attempt to ensure that benefits of tourism are better distributed and serve the needs of the local and broader community in terms of infrastructure development and improvement of social services and facilities

A Prospective, Multicenter, Randomized Study of Anti-CCR4 Monoclonal Antibody Mogamulizumab Versus Investigator's Choice in the Treatment of Patients with Relapsed/Refractory Adult T-Cell Leukemia-Lymphoma: Overall Response Rate, Progression-Free Survival, and Overall Survival

Abstract Introduction: Adult T-cell Leukemia-Lymphoma (ATL) is a rare malignancy of T-cells infected with HTLV-1 and has the worst prognosis of the T-cell lymphomas. CC chemokine receptor 4 (CCR4) is overexpressed on ATL cells (>90% of ATL patients [pts]). Mogamulizumab (Moga) is a monoclonal antibody directed against CCR4 that has been approved in Japan for the treatment of CCR4+ ATL. There is no standard or effective treatment for relapsed/refractory (R/R) ATL pts outside of Japan. Methods: Pts from the USA, EU, and Latin America with R/R ATL (acute, lymphoma, and chronic subtypes) were randomized 2:1 to treatment with Moga, 1.0 mg/kg, given weekly for the first 4-week cycle and then biweekly, or to 1 of 3 investigator choice (IC) regimens (gemcitabine/oxaliplatin, DHAP, or pralatrexate). Pts randomized to the IC arm were permitted to cross over to Moga upon progression. The primary endpoint was confirmed objective response rate (ORR), defined as a response that is maintained for approximately 8 weeks, in those randomized to the Moga arm (based on modified Tsukasaki criteria). ORR was assessed by the treating investigator (IA) and in blinded fashion by independent review (IR). Key secondary endpoints were ORR for IC and after cross over to Moga, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results: 71 pts were randomized (47 to Moga, 24 to IC). Tissue /blood from 65/71 pts (91.5%) expressed CCR4. Although randomized, there were baseline imbalances in known ATL prognostic factors. Pts with adverse prognostic features were more often randomized to Moga: these features included older age, poor ECOG performance status of 2, bone marrow involvement, and refractory to (vs having relapsed from) their most recent ATL therapy. Based on data through 31 March 2016, ORR (all responses, confirmed and unconfirmed) by IA was 34.0% (16/47) in the Moga group and 0% (0/24) in the IC group; these rates were largely concordant with ORR findings by IR of 27.7% (13/47) for the Moga group and 8.3% (2/24) for the IC group. Confirmed ORR for Moga was 14.9%; there were no confirmed responses in the IC group. 18 IC pts crossed over to Moga and 3 responded, including one confirmed response. The median (m) DoR for Moga was 5.65 months [mo] (95% CI 3.63, not reached). Two pts had responses lasting >9 mo. The 16 responders in the Moga arm (as assessed by IA) were evenly distributed over ATL subtypes: chronic 5/16 (31%), acute 5/16 (31%), and lymphoma 6/16 (38%). Of the 65 pts with any exposure to Moga (randomized plus crossover), response according to subtype was: chronic 5/10 (50%), acute 7/31 (23%), and lymphoma 7/24 (29%). While the study was not powered to demonstrate a difference between the treatment arms, the Kaplan-Meier plots of PFS and OS for the ITT population are presented below. The PFS curves deviate modestly in favor of the Moga group. The mPFS for Moga was 0.93 mo (min-max: 0.03-26.20 mo) with 21.5% of subjects progression free at 3 mo, while the mPFS for IC was 0.88 mo (0-4.23 mo) with 12.5 % of subjects progression free at 3 mo. The OS curves overlap. The mOS for the Moga arm was 4.90 mo (0.27-37.33 mo) with 38.9% alive at 12 mo, and the mOS for the IC arm was 6.87 mo ( 0.57-33.87 mo) with 37.5% alive at 12 mo. The OS curves may have been affected by the imbalance in prognostic factors and are confounded by the crossover of 75% of IC pts to Moga. Treatment emergent adverse events (TEAEs) occurring more often in the Moga group than the IC group were infections (51.1% vs 20.8%); respiratory disorders (48.9% vs 29.2%); infusion related reactions (46.8% vs 0%); and skin disorders (42.6% vs 8.3%). TEAEs ≥Grade 3 were 29/47 (61.7%) for Moga and 13/24 (54.2%) for IC. With the exception of known Moga-related events (infusion related reactions and drug eruptions), TEAE rates are similar when adjusted for exposure time to Moga or IC; for example, the AE rate per pt-mo of exposure for infections is 0.296 for the Moga group vs. 0.234 for the IC group. Conclusions: In the largest randomized clinical trial of pts with R/R ATL thus far conducted, commonly used cytotoxic regimens provided limited to no therapeutic benefit whereas treatment with Moga resulted in objective responses, a trend for favorable PFS, no clear survival advantage or disadvantage, and adverse events that are predictable, thereby supporting Moga's therapeutic potential in this setting. Figure Figure. Disclosures Phillips: Takeda: Speakers Bureau; Kyowa Kirin: Research Funding; Celgene: Speakers Bureau. Hermine:AB science: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Celgene: Research Funding; Novartis: Research Funding; Alexion: Research Funding. Lill:Kite: Research Funding; California Cord Blood Services: Consultancy; Sanofi: Speakers Bureau. Feldman:Seattle Genetics: Consultancy, Research Funding, Speakers Bureau; Abbvie/Pharmacyclics/Janssen: Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Sawas:Gilead Sciences: Speakers Bureau; Seattle Genetics: Honoraria. Cook:Kyowa Kirin Pharmaceutical Development, Inc.: Consultancy. Kurman:Kyowa Kirin Pharmaceutical Development, Inc: Consultancy. George:Kyowa Kirin Pharmaceutical Development: Employment. Dwyer:Kyowa Kirin Pharmaceutical Development, Inc.: Employment. Leoni:Kyowa Kirin Pharmaceutical Development, Inc.: Employment. Gonsky:Bioclinica: Other: Compensation for independent review of trial data. Horwitz:Infinity Pharmaceuticals: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Spectrum Pharmaceuticals: Consultancy, Honoraria, Research Funding; Kyowa Kirin Pharmaceutical: Research Funding; Millennium Pharmaceuticals: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Huya Bioscience International: Consultancy, Honoraria; Forty Seven, Inc.: Consultancy, Honoraria; ADC Therapeutics: Other: Travel

Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study.

BackgroundImmunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined.ObjectiveThis analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors.MethodsClinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed.ResultsWe confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS.ConclusionsPatients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (&gt;59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P &lt;.001). Overall motor and cognitive performance (P &lt;.001) were worse, however only disease motor progression was slower (coefficient, −0.58; SE 0.16; P &lt;.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P &lt;.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P &lt;.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients