Neorealism and the Organization of American States (OAS): an examination of CARICOM rationality toward Venezuela and the United States

Since 2017, CARICOM member states have been divided in the positions they take on Organization of American States (OAS) resolutions addressing political instability in Venezuela. This article uses a neorealism framework to determine whether or not the provision of energy investments by Venezuela and the United States to CARICOM member countries is an attempt on their part to skew the OAS voting mechanism in their national interests. The article also examines the extent to which CARICOM member states’ response to Venezuela’s and United States’ interest in the OAS demonstrates a pattern of rationality. The findings suggest that though the OAS provides a medium for states to negotiate mutually beneficial solutions, states are rational actors and even where they do corporate, dominant states may try to manifest their self-interest

Lifeworld Inc. : and what to do about it

Can we detect changes in the way that the world turns up as they turn up? This paper makes such an attempt. The first part of the paper argues that a wide-ranging change is occurring in the ontological preconditions of Euro-American cultures, based in reworking what and how an event is produced. Driven by the security – entertainment complex, the aim is to mass produce phenomenological encounter: Lifeworld Inc as I call it. Swimming in a sea of data, such an aim requires the construction of just enough authenticity over and over again. In the second part of the paper, I go on to argue that this new world requires a different kind of social science, one that is experimental in its orientation—just as Lifeworld Inc is—but with a mission to provoke awareness in untoward ways in order to produce new means of association. Only thus, or so I argue, can social science add to the world we are now beginning to live in

Chronic Stress, Sense of Belonging, and Depression Among Survivors of Traumatic Brain Injury

To test whether chronic stress, interpersonal relatedness, and cognitive burden could explain depression after traumatic brain injury (TBI). Design : A nonprobability sample of 75 mild-to-moderately injured TBI survivors and their significant others, were recruited from five TBI day-rehabilitation programs. All participants were within 2 years of the date of injury and were living in the community. Methods : During face-to-face interviews, demographic information, and estimates of brain injury severity were obtained and participants completed a cognitive battery of tests of directed attention and short-term memory, responses to the Perceived Stress Scale, Interpersonal Relatedness Inventory, Sense of Belonging Instrument, Neurobehavioral Functioning Inventory, and Center for Epidemiological Studies Depression Scale;. Findings : Chronic stress was significantly and positively related to post-TBI depression. Depression and postinjury sense of belonging were negatively related. Social support and results from the cognitive battery did not explain depression. Conclusions : Postinjury chronic stress and sense of belonging were strong predictors of post-injury depression and are variables amenable to interventions by nurses in community health, neurological centers, or rehabilitation clinics. Future studies are needed to examine how these variables change over time during the recovery process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72593/1/j.1547-5069.2002.00221.x.pd

Abnormal Type I Collagen Post-translational Modification and Crosslinking in a Cyclophilin B KO Mouse Model of Recessive Osteogenesis Imperfecta

Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause recessively inherited osteogenesis imperfecta type IX, a moderately severe to lethal bone dysplasia. To investigate the role of CyPB in collagen folding and post-translational modifications, we generated Ppib−/− mice that recapitulate the OI phenotype. Knock-out (KO) mice are small, with reduced femoral areal bone mineral density (aBMD), bone volume per total volume (BV/TV) and mechanical properties, as well as increased femoral brittleness. Ppib transcripts are absent in skin, fibroblasts, femora and calvarial osteoblasts, and CyPB is absent from KO osteoblasts and fibroblasts on western blots. Only residual (2–11%) collagen prolyl 3-hydroxylation is detectable in KO cells and tissues. Collagen folds more slowly in the absence of CyPB, supporting its rate-limiting role in folding. However, treatment of KO cells with cyclosporine A causes further delay in folding, indicating the potential existence of another collagen PPIase. We confirmed and extended the reported role of CyPB in supporting collagen lysyl hydroxylase (LH1) activity. Ppib−/− fibroblast and osteoblast collagen has normal total lysyl hydroxylation, while increased collagen diglycosylation is observed. Liquid chromatography/mass spectrometry (LC/MS) analysis of bone and osteoblast type I collagen revealed site-specific alterations of helical lysine hydroxylation, in particular, significantly reduced hydroxylation of helical crosslinking residue K87. Consequently, underhydroxylated forms of di- and trivalent crosslinks are strikingly increased in KO bone, leading to increased total crosslinks and decreased helical hydroxylysine- to lysine-derived crosslink ratios. The altered crosslink pattern was associated with decreased collagen deposition into matrix in culture, altered fibril structure in tissue, and reduced bone strength. These studies demonstrate novel consequences of the indirect regulatory effect of CyPB on collagen hydroxylation, impacting collagen glycosylation, crosslinking and fibrillogenesis, which contribute to maintaining bone mechanical properties

Phase i trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours

BACKGROUND: This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective secondgeneration inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours. METHODS: In all, 49 patients received axitinib 5mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5mg b.i.d. with paclitaxel/carboplatin. RESULTS: Two patients experienced dose-limiting toxicities: febrile neutropenia (n¼1) in the paclitaxel/carboplatin cohort and fatigue (n¼1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No gradeX3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n¼27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n¼21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination. CONCLUSION: Axitinib 5mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug–drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.This study was sponsored by Pfizer Inc. Support was provided in part by National Institutes of Health grant P30 CA006927 to the Fox Chase Cancer Center. We thank the patients who participated in this study and the physicians who referred them, as well as the study coordinators and data managers, Shelley Mayfield and Carol Martins at Pfizer Inc. for support of the study conduct, and Gamal ElSawah, Pfizer Medical Affairs, for his review of the manuscript. Medical writing support was provided by Joanna Bloom, of UBC Scientific Solutions (Southport, CT, USA) and Christine Arris at ACUMED (Tytherington, UK) and was funded by Pfizer In

Antiangiogenic therapy for breast cancer

Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria