The Environmental Impacts of International Finance Corporation Lending and Proposals for Reform: A Case Study of Conservation and Oil Development in the Guatemalan Petén

This Article presents a case study of lending by the International Finance Corporation (IFC), the private-sector lending arm of the World Bank Group, in the oil and gas sector in Guatemala. The case study emphasizes the need for additional environmental reform at IFC. With two separate loans in 1994 and 1996, IFC supported the activities of a small international oil company that was operating within a national park in the northern Guatemalan Petdn, an area of rich tropical forests and globally important wetlands. The company\u27s operations had been grandfathered in to the park upon its creation in 1990. Funding from IFC was used to construct a pipeline from the oil field in the park to a refinery outside of the park. The crux of the authors\u27 findings is that the pipeline should have been constructed to follow the path of an existing road, rather than along the chosen route that crosses significant stretches of primary tropical forest and that opened a new right-of-way into a park already facing continued pressure from colonization. The authors conclude that a stronger set of IFC lending policies, combined with a better environmental impact assessment and more extensive public consultation, would have led to a less environmentally damaging outcome. Although the authors acknowledge the complex questions about the role of governments, development agencies, the private sector, conservation organizations, and local communities raised by this issue, they focus on the narrow subject of IFC\u27s role in this matter, stressing the need for a reform agenda at that institution

Maternal vitamin D deficiency and developmental origins of health and disease (DOHaD)

Vitamin D is an essential nutrient that is metabolized in the body to generate an active metabolite (1, 25(OH)2D) with hormone-like activity and highly diverse roles in cellular function. Vitamin D deficiency (VDD) is a prevalent but easily p reventable nutritional disturbance. Emerging evidence demonstrates the importance of s ufficient vitamin D concentrations during fetal life with deficiencies leading to long-term effects into adulthood. Here, we provide a detailed review and perspective of evidence for the role of maternal VDD in offspring long-term health, particularly as it relates to developmental origins of health and disease (DOHaD). We focus on the roles in neurobehavioral and cardiometabolic disorders in humans and highlight recent finding s from zebrafish and rodent models that probe potential mechanisms linking early life VDD to later life health outcomes. Moreover, we explore evidence implicating epigenetic mechanisms as a mediator of this link. Gaps in our current understanding of how maternal VDD might result in deleterious offspring outcomes later in life are also addressed

A New Upper Limit for the Tau-Neutrino Magnetic Moment

Using a prompt neutrino beam in which a nu_tau component was identified for the first time, the nu_tau magnetic moment was measured based on a search for an anomalous increase in the number of neutrino-electron interactions. One such event was observed when 2.3 were expected from background processes, giving an upper 90% confidence limit of 3.9x10^-7 Bohr magnetons.Comment: 9 pages; 1 figur

Using confirmatory factor analysis to evaluate construct validity of the Brief Pain Inventory (BPI)

Context: The Brief Pain Inventory (BPI) is a frequently used instrument designed to assess the patient-reported outcome of pain. The majority of factor analytic studies have found a two-factor (i.e., pain intensity and pain interference) structure for this instrument; however, because the BPI was developed with an a priori hypothesis of the relationship among its items, it follows that construct validity investigations should use confirmatory factor analysis (CFA). Objectives: The purpose of this work was to establish the construct validity of the BPI using a CFA framework and demonstrate factorial invariance using a range of demographic variables. Methods: A retrospective CFA was completed in a sample of individuals diagnosed with HIV/AIDS and cancer (n = 364; 63% male; age 21-92 years, M = 51.80). A baseline one-factor model was compared against two-factor and three-factor models (i.e., pain intensity, activity interference, and affective interference) that were developed based on the hypothetical design of the instrument. Results: Fit indices for the three-factor model were statistically superior when compared with the one-factor model and marginally better when compared with the two-factor model. This three-factor structure was found to be invariant across disease, age, and ethnicity groups. Conclusion: The results of this study provide evidence to support a three-factor representation of the BPI, and the originally hypothesized two-factor structure. Such findings will begin to provide clinical trialists, pharmaceutical sponsors, and regulators with confidence in the psychometric properties of this instrument when considering its inclusion in clinical research

Observation of Tau Neutrino Interactions

The DONUT experiment has analyzed 203 neutrino interactions recorded in nuclear emulsion targets. A decay search has found evidence of four tau neutrino interactions with an estimated background of 0.34 events. This number is consistent with the Standard Model expectation.Comment: 12 pages, 3 figures, PD

The delivery of personalised, precision medicines via synthetic proteins

Introduction: The design of advanced drug delivery systems based on synthetic and su-pramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. The Problem: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The Solution: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein the use of synthetic proteins for drug delivery has been reviewed

Growth Hormone Research Society perspective on biomarkers of GH action in children and adults

Objective The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. Participants GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Evidence Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Consensus process Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. Conclusions The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly

Erratum: Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome (J. Exp. Med. (2020) 217:6 Doi:10.1084/jem.20191804)

The authors regret that in the original version of Table S1, the column for patient 12 was mistakenly duplicated in the column for patient 8. The online Table S1 PDF has been corrected. The error appears only in PDFs downloaded before June 4, 2020