State of the art:understanding and integration of the social context in diabetes care

We review the past 25 years of research addressing challenges people living with diabetes experience in their daily lives related to social contexts, i.e. in their family, at work and in society at large, and identify research gaps. We found that young people with diabetes, as they develop through to adulthood, are exposed to considerable risks to their physical and mental health. Family-system interventions have had mixed outcomes. Research in this area would benefit from attention to ethnic/cultural diversity, and involving fathers and other family members. In adults with diabetes, social support relates to better diabetes outcomes. While family member involvement in care is likely to affect health and psychosocial outcomes of the person with diabetes, key elements and mediators of effective family interventions need to be identified. The challenges of diabetes management at work are under-researched; distress and intentional hyperglycaemia are common. When depression is comorbid with diabetes, there are increased work-related risks, e.g. unemployment, sickness absence and reduced income. Research to support people with diabetes at work should involve colleagues and employers to raise awareness and create supportive environments. Stigma and discrimination have been found to be more common than previously acknowledged, affecting self-care, well-being and access to health services. Guidance on stigma-reducing choice of language has been published recently. Resilience, defined as successful adaptation to adversity such as stigma and discrimination, requires studies relevant to the specific challenges of diabetes, whether at diagnosis or subsequently. The importance of the social context for living well with diabetes is now fully recognized, but understanding of many of the challenges, whether at home or work, is still limited, with much work needed to develop successful interventions

The latitudinal temperature gradient and its climate dependence as inferred from foraminiferal δ18O over the past 95 million years

The latitudinal temperature gradient is a fundamental state parameter of the climate system tied to the dynamics of heat transport and radiative transfer. Thus, it is a primary target for temperature proxy reconstructions and global climate models. However, reconstructing the latitudinal temperature gradient in past climates remains challenging due to the scarcity of appropriate proxy records and large proxy–model disagreements. Here, we develop methods leveraging an extensive compilation of planktonic foraminifera δ18O to reconstruct a continuous record of the latitudinal sea-surface temperature (SST) gradient over the last 95 million years (My). We find that latitudinal SST gradients ranged from 26.5 to 15.3 °C over a mean global SST range of 15.3 to 32.5 °C, with the highest gradients during the coldest intervals of time. From this relationship, we calculate a polar amplification factor (PAF; the ratio of change in >60° S SST to change in global mean SST) of 1.44 ± 0.15. Our results are closer to model predictions than previous proxy-based estimates, primarily because δ18O-based high-latitude SST estimates more closely track benthic temperatures, yielding higher gradients. The consistent covariance of δ18O values in low- and high-latitude planktonic foraminifera and in benthic foraminifera, across numerous climate states, suggests a fundamental constraint on multiple aspects of the climate system, linking deep-sea temperatures, the latitudinal SST gradient, and global mean SSTs across large changes in atmospheric CO2, continental configuration, oceanic gateways, and the extent of continental ice sheets. This implies an important underlying, internally driven predictability of the climate system in vastly different background states

The enigma of Oligocene climate and global surface temperature evolution.

Falling atmospheric CO2 levels led to cooling through the Eocene and the expansion of Antarctic ice sheets close to their modern size near the beginning of the Oligocene, a period of poorly documented climate. Here, we present a record of climate evolution across the entire Oligocene (33.9 to 23.0 Ma) based on TEX86 sea surface temperature (SST) estimates from southwestern Atlantic Deep Sea Drilling Project Site 516 (paleolatitude ∼36°S) and western equatorial Atlantic Ocean Drilling Project Site 929 (paleolatitude ∼0°), combined with a compilation of existing SST records and climate modeling. In this relatively low CO2 Oligocene world (∼300 to 700 ppm), warm climates similar to those of the late Eocene continued with only brief interruptions, while the Antarctic ice sheet waxed and waned. SSTs are spatially heterogenous, but generally support late Oligocene warming coincident with declining atmospheric CO2 This Oligocene warmth, especially at high latitudes, belies a simple relationship between climate and atmospheric CO2 and/or ocean gateways, and is only partially explained by current climate models. Although the dominant climate drivers of this enigmatic Oligocene world remain unclear, our results help fill a gap in understanding past Cenozoic climates and the way long-term climate sensitivity responded to varying background climate states

Bounded Influence Regression in the Presence of Heteroskedasticity of Unknown Form

In a regression model with conditional heteroskedasticity of unknown form, we propose a general class of M-estimators scaled by nonparametric estimates of the conditional standard deviations of the dependent variable. We give regularity conditions under which these estimators are asymptotically equivalent to M-estimators scaled by the true conditional standard deviations. The practical performance of these estimators is investigated through a Monte Carlo experiment

The Relationship Between HR Practices and Firm Performance: Examining Causal Order

Significant research attention has been devoted to examining the relationship between HR practices and firm performance, and the research support has assumed HR as the causal variable. Using data from 45 business units (with 62 data points), this study examines how measures of HR practices correlate with past, concurrent, and future operational performance measures. The results indicate that correlations with performance measures at all three times are both high and invariant, and that controlling for past or concurrent performance virtually eliminates the correlation of HR with future performance. Implications are discussed

Trypanocidal and leishmanicidal activity of six limonoids

Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their trypanocidal and leishmanicidal activities using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. Whereas all compounds showed anti-trypanosomal activity, only compounds 1–4 displayed anti-leishmanial activity. The 50% growth inhibition (GI 50) values for the trypanocidal and leishmanicidal activity of the compounds ranged between 2.5 and 14.9 μM. Kotschyienone A (1) was found to be the most active compound with a minimal inhibition concentration (MIC) value of 10 μM and GI 50 values between 2.5 and 2.9 μM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and GI 50 values of 100 μM and 31.5–46.2 μM, respectively. Compound 1 was also found to show activity against intracellular amastigotes of L. major with a GI 50 value of 1.5 μM. The results suggest that limonoids have potential as drug candidates for the development of new treatments against trypanosomiasis and leishmaniasis

Rudimentary G-Quadruplex-Based Telomere Capping In Saccharomyces Cerevisiae

Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show that protein-bound G4 DNA at a 3\u27 overhang inhibits 5\u27-\u3e 3\u27 resection of a paired strand by exonuclease I. These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo

In vitro growth inhibition of bloodstream forms of Trypanosoma brucei and Trypanosoma congolense by iron chelators

African trypanosomes exert significant morbidity and mortality in man and livestock. Only a few drugs are available for the treatment of trypanosome infections and therefore, the development of new anti-trypanosomal agents is required. Previously it has been shown that bloodstream-form trypanosomes are sensitive to the iron chelator deferoxamine. In this study the effect of 13 iron chelators on the growth of Trypanosoma brucei, T. congolense and human HL-60 cells was tested in vitro. With the exception of 2 compounds, all chelators exhibited anti-trypanosomal activities, with 50% inhibitory concentration (IC(50)) values ranging between 2.1 – 220 μM. However, the iron chelators also displayed cytotoxicity towards human HL-60 cells and therefore, only less favourable selectivity indices compared to commercially available drugs. Interfering with iron metabolism may be a new strategy in the treatment of trypanosome infections. More specifically, lipophilic iron-chelating agents may serve as lead compounds for novel anti-trypanosomal drug development

Change escalation processes and complex adaptive systems: from incremental reconfigurations to discontinuous restructuring

This study examines when “incremental” change is likely to trigger “discontinuous” change, using the lens of complex adaptive systems theory. Going beyond the simulations and case studies through which complex adaptive systems have been approached so far, we study the relationship between incremental organizational reconfigurations and discontinuous organizational restructurings using a large-scale database of U.S. Fortune 50 industrial corporations. We develop two types of escalation process in organizations: accumulation and perturbation. Under ordinary conditions, it is perturbation rather than the accumulation that is more likely to trigger subsequent discontinuous change. Consistent with complex adaptive systems theory, organizations are more sensitive to both accumulation and perturbation in conditions of heightened disequilibrium. Contrary to expectations, highly interconnected organizations are not more liable to discontinuous change. We conclude with implications for further research, especially the need to attend to the potential role of managerial design and coping when transferring complex adaptive systems theory from natural systems to organizational systems