Cardiovascular disease in the Peruvian Andes: local perceptions, barriers, and paths to preventing chronic diseases in the Cajamarca region

Objectives: Public health interventions can be improved by understanding peoples' explanatory models of disease. We explore awareness and perceptions of cardiovascular diseases (CVD) and options for preventative actions in young adults living in rural Andean communities. Methods: We used convenience sampling to select 46 men and women from communities in Cajamarca (Peru). Subjects participated in eight focus groups where they discussed their understanding and perceived causes of CVD as well as barriers and pathways to healthy lifestyles. Results: Fresh foods, physical activity, unpleasant emotions, and healthcare access were cited as important determinants of healthy lifestyles. Barriers to healthy diets included lacking nutritional knowledge, fluctuating food prices, and limited access to foodstuffs. Women felt particularly vulnerable to CVD and identified gendered barriers to manage stress and engage in sports. Low health literacy, poor doctor-patient relationships, and long distances prevented participants from fully accessing healthcare. Conclusion: CVD prevention interventions should consider local knowledge of these diseases and of healthy lifestyles, and harness ongoing programmes that have successfully promoted good nutrition in children and pregnant women. In concert with public-private parterships, governments should include disease prevention interventions for the entire family

Sivelestat relieves respiratory distress refractory to dexamethasone in all-trans retinoic acid syndrome: a report of two cases

Kawasaki K, Akaike H, Miyauchi A, Ouchi K. Sivelestat relieves respiratory distress refractory to dexamethasone in all-trans retinoic acid syndrome: a report of two cases. Treatment with all-trans retinoic acid (ATRA) improves the prognosis of patients with acute promyelocytic leukemia (APL), but ATRA syndrome may occur as a possible fatal side effect, especially in cases refractory to medication or involving pulmonary hemorrhage. We describe two patients with APL who suffered from intracranial hemorrhage. The first patient was a 16-yr-old girl who was treated with ATRA and then developed respiratory distress refractory to treatment with dexamethasone combined with anthracycline-cytarabine cytoreduction therapy. Treatment with Sivelestat, a small molecule inhibitor of neutrophil elastase, achieved rapid improvement in oxygenation and chest radiograph findings, and the patient has been in complete remission for 24 months. The second patient was a 10-yr-old boy in whom pulmonary hemorrhage developed following administration of ATRA, dexamethasone and cytoreduction therapy. Aspiration and administration of Sivelestat improved oxygenation and he remained stable. Hematological improvement was also achieved, but the patient died of brain dysfunction because of cerebral edema accompanied by intracranial bleeding. The two cases suggest that Sivelestat may be effective as an additional agent in the treatment of refractory ATRA syndrome, and, therefore, prospective randomized studies of treatment protocols are warranted

Gender based water violence: cross cultural evidence of severe harm associated with water insecurity for women and girls

We examined how study participants in Indonesia and Peru viewed the relationship between water insecurity and women's health via thematic analysis of interviews and focus groups. Participants reported that water insecurity led to vaginal infections, miscarriage, premature births, uterine prolapse, poor nutrition, restricted economic opportunities, and intergenerational cycles of poverty. Participants in both countries stated that extreme burdens associated with water insecurity should be categorized as violence. Based on these findings, we developed the concept of “gender-based water violence,” defined as the spectrum of stressors associated with water insecurity that are so severe as to threaten human health and well-being, particularly that of women and girls

A "cookbook" for vulnerability research

There is a growing need to facilitate the interdisciplinary study of the relationship between the environment and human health and well-being. It is increasingly recognized that vulnerability is a key construct allowing discipline-specific research questions on these topics to be meaningfully contextualized. However, there is little consensus regarding the meaning of the concept of vulnerability or how it can best be utilized in research studies. In this perspective article, we use the metaphor of a "cookbook" to review promising trends in vulnerability research and to make this body of research accessible to a multi-disciplinary audience. Specifically, we discuss a selection of "recipes" (theoretical frameworks), "ingredients" (vulnerability domains), "cooking tools" (qualitative and quantitative methods), and approaches to "meal presentation" (communication of results) drawn from vulnerability studies published in the past 15 years. Our aim is for this short "cookbook" to serve as a jumping-off point for scholars unfamiliar with the vulnerability literature and an inspiration for scholars more familiar with this topic to develop new ways to navigate the tension between locally-specific assessments of vulnerability and attempts at standardization. Our ultimate take-home message is that the specifics theories and methods used in vulnerability research are less important than attention to what we see as the 3 'T's of transparency, triangulation, and transferability, and to efforts to make vulnerability research both "place-based" and comparable

Cyclophosphamide- metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study

Abstract Introduction Cyclophosphamide-based adjuvant chemotherapy is a mainstay of treatment for women with node-positive breast cancer, but is not universally effective in preventing recurrence. Pharmacogenetic variability in drug metabolism is one possible mechanism of treatment failure. We hypothesize that functional single nucleotide polymorphisms (SNPs) in drug metabolizing enzymes (DMEs) that activate (CYPs) or metabolize (GSTs) cyclophosphamide account for some of the observed variability in disease outcomes. Methods We performed a retrospective cohort study of 350 women enrolled in a multicenter, randomized, adjuvant breast cancer chemotherapy trial (ECOG-2190/INT-0121). Subjects in this trial received standard-dose cyclophosphamide, doxorubicin and fluorouracil (CAF), followed by either observation or high-dose cyclophosphamide and thiotepa with stem cell rescue. We used bone marrow stem cell-derived genomic DNA from archival specimens to genotype CYP2B6, CYP2C9, CYP2D6, CYP3A4, CYP3A5, GSTM1, GSTT1, and GSTP1. Cox regression models were computed to determine associations between genotypes (individually or in combination) and disease-free survival (DFS) or overall survival (OS), adjusting for confounding clinical variables. Results In the full multivariable analysis, women with at least one CYP3A4 *1B variant allele had significantly worse DFS than those who were wild-type *1A/*1A (multivariate hazard ratio 2.79; 95% CI 1.52, 5.14). CYP2D6 genotype did not impact this association among patients with estrogen receptor (ER) -positive tumors scheduled to receive tamoxifen. Conclusions These data support the hypothesis that genetic variability in cyclophosphamide metabolism independently impacts outcome from adjuvant chemotherapy for breast cancer

Vertical integration for full outsourcing: growth and internationalization of a portuguese packaging firm

Based on a case study of a Portuguese packaging firm, this paper examines how vertical integration of the supplier serves as a vehicle for the full outsourcing of the client firms' needs in a solution that reduces transaction costs, favors specialization, and permits small and mediumsized firms to develop competencies that may be exploited in a wide array of projects. Vertical integration by the supplier (a governance decision) is a strategic response to changes in the sourcing model of the clients. Client-supplier relationships have inter-spatial and inter-temporal value that surpasses spot market exchanges

Mutated Ptpn11 alters leukemic stem cell frequency and reduces the sensitivity of acute myeloid leukemia cells to Mcl1 inhibition

PTPN11 encodes the Shp2 non-receptor protein-tyrosine phosphatase implicated in several signaling pathways. Activating mutations in Shp2 are commonly associated with juvenile myelomonocytic leukemia but are not as well defined in other neoplasms. Here we report that Shp2 mutations occur in human acute myeloid leukemia (AML) at a rate of 6.6% (6/91) in the ECOG E1900 data set. We examined the role of mutated Shp2 in leukemias harboring MLL translocations, which co-occur in human AML. The hyperactive Shp2E76K mutant, commonly observed in leukemia patients, significantly accelerated MLL-AF9-mediated leukemogenesis in vivo. Shp2E76K increased leukemic stem cell frequency and affords MLL-AF9 leukemic cells IL3 cytokine hypersensitivity. As Shp2 is reported to regulate anti-apoptotic genes, we investigated Bcl2, Bcl-xL and Mcl1 expression in MLL-AF9 leukemic cells with and without Shp2E76K. Although the Bcl2 family of genes was upregulated in Shp2E76K cells, Mcl1 showed the highest upregulation in MLL-AF9 cells in response to Shp2E76K. Indeed, expression of Mcl1 in MLL-AF9 cells phenocopies expression of Shp2E76K, suggesting Shp2 mutations cooperate through activation of anti-apoptotic genes. Finally, we show Shp2E76K mutations reduce sensitivity of AML cells to small-molecule-mediated Mcl1 inhibition, suggesting reduced efficacy of drugs targeting MCL1 in patients with hyperactive Shp2

The economic geography of the meso-global spaces: integrating multinationals and clusters at the local-global level

This is an author's accepted manuscript of an article published in: “European Planning Studies"; Volume 21, Issue 7, 2013; copyright Taylor & Francis; available online at: http://dx.doi.org/10.1080/09654313.2013.733853[EN] The local global phenomenon literature is fragmented between the fields of international business and economic geography (EG). In the case of the latter, the literature, produced within the global production networks (GPNs) and global value chain frameworks, does not address the central role of firms, especially multinationals which co-locate and connect territories along GPNs. This paper develops a cross-field conceptual integration in order to enrich the EG perspective, using qualitative research methodology to test the framework. The results have important implications for scholars and policymakers.We are very thankful to the “Ministry of Economics” funding ECO2010:17318 and “Generalitat Valenciana” for its support in visiting the London School of Economics and Political Science (BEST 2011 grants)Hervás Oliver, JL.; Boix Domenech, R. (2012). The economic geography of the meso-global spaces: integrating multinationals and clusters at the local-global level. European Planning Studies. 21(7):1064-1080. https://doi.org/10.1080/09654313.2013.733853S1064108021