Timing and causes of North African wet phases during the last glacial period and implications for modern human migration

We present the first speleothem-derived central North Africa rainfall record for the last glacial period. The record reveals three main wet periods at 65-61 ka, 52.5-50.5 ka and 37.5-33 ka that lead obliquity maxima and precession minima. We find additional minor wet episodes that are synchronous with Greenland interstadials. Our results demonstrate that sub-tropical hydrology is forced by both orbital cyclicity and North Atlantic moisture sources. The record shows that after the end of a Saharan wet phase around 70 ka ago, North Africa continued to intermittently receive substantially more rainfall than today, resulting in favourable environmental conditions for modern human expansion. The encounter and subsequent mixture of Neanderthals and modern humans – which, on genetic evidence, is considered to have occurred between 60 and 50 ka – occurred synchronously with the wet phase between 52.5 and 50.5 ka. Based on genetic evidence the dispersal of modern humans into Eurasia started less than 55 ka ago. This may have been initiated by dry conditions that prevailed in North Africa after 50.5 ka. The timing of a migration reversal of modern humans from Eurasia into North Africa is suggested to be coincident with the wet period between 37.5 and 33 ka

Responses and relationship dynamics of men and their spouses during active surveillance for prostate cancer: health literacy as an inquiry framework

BACKGROUND: Early stage prostate cancer patients may be allocated to active surveillance, where the condition is observed over time with no intervention. Living with a cancer diagnosis may impose stress on both the men and their spouses. In this study we explore whether the scores of and verbal responses to a Health Literacy Questionnaire can be used to identify individuals in need of information and support and to reveal differences in perception and understanding in health related situations within couples. METHODS: We used the nine-domain Health Literacy Questionnaire (HLQ) as a framework to explore health literacy in eight couples where the men were on active surveillance for prostate cancer progression. Scores were calculated for each domain for both individuals. For each couple differences in scores were also calculated and related to the informants\u27 self-reported experiences and reflections in relation to participating in an active surveillance program. Also an inductive analysis was performed to identify themes in the responses and these themes were compared to those of HLQ. RESULTS: The men tended to score higher than their spouses. There was no consistent relation between scores and the reported experiences and reflections. However, some interesting patterns emerged, e.g. in two of the three couples with the largest within couple differences in HLQ scores, responses revealed discrepancies in how the men and their spouses perceived their situation. Also, three themes emerged which related to six of the HLQ domains, i.e. involvement of spouses and other people around the men; support from and interaction with healthcare professionals; and use of the Internet for information retrieval. CONCLUSIONS: Using the HLQ as an interview framework provided insight into the differences within couples and provided new perspectives on their experiences, including their contact with health professionals and the patient-spouse interaction when dealing with prostate cancer. The HLQ used as a dialogue tool may be an adjunct to assist healthcare providers to understand the need for support and information of men with prostate cancer on active surveillance and the dynamics within couples

Cultural adaptation and validation of the Health Literacy Questionnaire (HLQ): robust nine-dimension Danish language confirmatory factor model

Health literacy is an important construct in population health and healthcare requiring rigorous measurement. The Health Literacy Questionnaire (HLQ), with nine scales, measures a broad perception of health literacy. This study aimed to adapt the HLQ to the Danish setting, and to examine the factor structure, homogeneity, reliability and discriminant validity. The HLQ was adapted using forward-backward translation, consensus conference and cognitive interviews (n = 15). Psychometric properties were examined based on data collected by face-to-face interview (n = 481). Tests included difficulty level, composite scale reliability and confirmatory factor analysis (CFA). Cognitive testing revealed that only minor re-wording was required. The easiest scale to respond to positively was \u27Social support for health\u27, and the hardest were \u27Navigating the healthcare system\u27 and \u27Appraisal of health information\u27. CFA of the individual scales showed acceptably high loadings (range 0.49-0.93). CFA fit statistics after including correlated residuals were good for seven scales, acceptable for one. Composite reliability and Cronbach\u27s α were >0.8 for all but one scale. A nine-factor CFA model was fitted to items with no cross-loadings or correlated residuals allowed. Given this restricted model, the fit was satisfactory. The HLQ appears robust for its intended application of assessing health literacy in a range of settings. Further work is required to demonstrate sensitivity to measure changes

The seawater neodymium and lead isotope record of the final stages of Central American Seaway closure

Key Points: Seawater Nd and Pb isotope records for the Pliocene Caribbean and EEP Caribbean Nd isotope composition became more UNADW-like during the Pliocene Short term changes support link between CAS closure and strength of AMOC The shoaling and final closure of the Central American Seaway (CAS) resulted in a major change of the global ocean circulation and has been suggested as an essential driver for strengthening of Atlantic Meridional Overturning Circulation (AMOC). The exact timing of CAS closure is key to interpreting its importance. Here we present a reconstruction of deep and intermediate water Nd and Pb isotope compositions obtained from fossil fish teeth and the authigenic coatings of planktonic foraminifera in the eastern equatorial Pacific (ODP Site 1241) and the Caribbean (ODP Sites 998, 999 and 1000) covering the final stages of CAS closure between 5.6 and 2.2 Ma. The data for the Pacific site indicate no significant Atlantic/Caribbean influence over this entire period. The Caribbean sites show a continuous trend to less radiogenic Nd isotope compositions during the Pliocene, consistent with an enhancement of Upper North Atlantic Deep Water (UNADW) inflow and a strengthening of the AMOC. Superimposed onto this long-term trend, shorter-term changes of intermediate Caribbean Nd isotope signatures approached more UNADW-like values during intervals when published reconstructions of seawater salinity suggested complete closure of the CAS. The data imply that significant deep water exchange with the Pacific essentially stopped by 7 Ma and that shallow exchange, which still occurred at least periodically until approximately 2.5 Ma, may have been linked to the strength of the AMOC but did not have any direct effect on the intermediate and deep Caribbean Nd isotope signatures through mixing with Pacific waters

National indicators of health literacy: ability to understand health information and to engage actively with healthcare providers - a population-based survey among Danish adults

Health literacy is a multidimensional concept covering a range of cognitive and social skills necessary for participation in health care. Knowledge of health literacy levels in general populations and how health literacy levels impacts on social health inequity is lacking. The primary aim of this study was to perform a population-based assessment of dimensions of health literacy related to understanding health information and to engaging with healthcare providers. Secondly, the aim was to examine associations between socio-economic characteristics with these dimensions of health literacy

BB rat Gimap gene expression in sorted lymphoid T and B cells

Aims: The Gimap gene family has been shown to be integral to T cell survival and development. A frameshift mutation in Gimap5, one of seven members of the Gimap family, results in lymphopenia and is a prerequisite for spontaneous type 1 diabetes (T1D) in the BioBreeding (BB) rat. While not contributing to lymphopenia, the Gimap family members proximal to Gimap5, encompassed within the Iddm39 quantitative trait locus (QTL), have been implicated in T1D. We hypothesized that expression of the Gimap family members within the Iddm39 QTL, during thymocyte development as well as in peripheral T and B cells contribute to T1D. Main methods: Cell sorted subpopulations were analyzed by quantitative real time (qRT) PCR. Key findings: Gimap4 expression was reduced in DR.(lyp/lyp) rat double negative, double positive and CD8 single positive (SP) thymocytes while expression of Gimap8, Gimap6, and Gimap7 was reduced only in CD8 SP thymocytes. Interestingly, expression of the entire Gimap gene family was reduced in DR.(lyp/lyp) rat peripheral T cells compared to non-lymphopenic, non-diabetic DR.(+/+) rats. With the exception of Gimap6. the Gimap family genes were not expressed in B cells from spleen and mesenteric lymph node (MLN). Expression of Gimap9 was only detected in hematopoietic cells of non B cell lineage such as macrophage, dendritic or NK cells. Significance: These results suggest that lack of the Gimap5 protein in the DR.(lyp/lyp) congenic rat was associated with impaired expression of the entire family of Gimap genes and may regulate T cell homeostasis in the peripheral lymphoid organs. (C) 2011 Elsevier Inc. All rights reserved

Higher health literacy is associated with better glycemic control in adults with type 1 diabetes:a cohort study among 1399 Danes

Aim: Self-management of diabetes is influenced by a range of factors including the ability to access, understand, appraise, and use of health information in everyday life, which can collectively be called health literacy. We investigated associations between nine domains of health literacy and HbA1c level in people with type 1 diabetes.Methods: A cross-sectional study was conducted with 1399 people with type 1 diabetes attending a Danish specialist diabetes clinic. Health literacy was assessed using the nine-domain Health Literacy Questionnaire. The association between health literacy and HbA1c was analyzed using linear regression with adjustment for age, sex, educational attainment and diabetes duration. Results: Of the 1399 participants, 50% were women, mean age was 54 years, and mean HbA1c was 61 mmol/mol (7.8%). Higher health literacy scores were associated with lower HbA1c levels across eight of nine health literacy domains. This association remained significant after adjusting for educational attainment. Among the domains, \u27Actively managing my health\u27 had the strongest impact on HbA1c. This was in turn predicted by \u27Appraising health information\u27, \u27Having sufficient information to manage health\u27, and \u27Social support for health\u27. Conclusions: Higher health literacy levels are associated with lower HbA1c regardless of educational background. This study highlights the importance of healthcare provision to respond to the health literacy levels of people with diabetes and to the possible need to provide program designed to enhance health literacy

Notch 1–Deficient Common Lymphoid Precursors Adopt a B Cell Fate in the Thymus

We have recently reported that Notch 1, a member of the Notch multigene family, is essential for the development of murine T cells. Using a mouse model in which Notch 1 is inactivated in bone marrow (BM) precursors we have shown that B cells instead of T cells are found in the thymus of BM chimeras. However, it is not clear whether these B cells develop by default from a common lymphoid precursor due to the absence of Notch 1 signaling, or whether they arise as a result of perturbed migration of BM-derived B cells and/or altered homeostasis of normal resident thymic B cells

Folding and trimerization of signal sequence-less mature TolC in the cytoplasm of Escherichia coli

TolC is a multifunctional outer-membrane protein (OMP) of Escherichia coli that folds into a unique α/β-barrel structure. Previous studies have shown that unlike the biogenesis of β-barrel OMPs, such as porins, TolC assembles independently from known periplasmic folding factors. Yet, the assembly of TolC, like that of β-barrel OMPs, is dependent on BamA and BamD, two essential components of the β-barrel OMP assembly machinery. We have investigated the folding properties and cellular trafficking of a TolC derivative that lacks the entire signal sequence (TolCΔ2–22). A significant amount of TolCΔ2–22 was found to be soluble in the cytoplasm, and a fraction of it folded and trimerized into a conformation similar to that of the normal outer membrane-localized TolC protein. Some TolCΔ2–22 was found to associate with membranes, but failed to assume a wild-type-like folded conformation. The null phenotype of TolCΔ2–22 was exploited to isolate suppressor mutations, the majority of which mapped in secY. In the secY suppressor background, TolCΔ2–22 resumed normal function and folded like wild-type TolC. Proper membrane insertion could not be achieved upon in vitro incubation of cytoplasmically folded TolCΔ2–22 with purified outer membrane vesicles, showing that even though TolC is intrinsically capable of folding and trimerization, for successful integration into the outer membrane these events need to be tightly coupled to the insertion process, which is mediated by the Bam machinery. Genetic and biochemical data attribute the unique folding and assembly pathways of TolC to its large soluble α-helical domain