Estrogen receptor-beta (ERβ) has been suggested to exert anti-inflammatory and anti-tumorigenic effects in the colon, providing a translational potential to prevent and/or treat inflammatory bowel disease (IBD) and its progression to colitis-associated colorectal cancer (CAC). However, the specific direct role of ERβ in CAC has not yet been tested. We assessed the effects of ERβ deficiency in the azoxymethane (AOM)/dextran sodium sulfate(DSS)-induced CAC model using ERβ knockout (βERKO) mice and wild-type (WT) littermates. These mice were injected with AOM followed by one week of DSS treatment, and sacrificed on weeks 9 or 16.βERKO mice developed more severe clinical colitis compared to WT mice, as evidenced by significantly higher disease activity index after DSS treatment, weight to length ratio of the colons, inflammation score, and grade of dysplasia. ERβ-deficient colons presented greater number and size of polyps at weeks 9 and 16, respectively, and were characterized by a significant increase in interleukin (IL)-6, IL-17, tumor necrosis factor alpha, and interferon-gamma mRNA levels. Furthermore, higher protein expression levels of nuclear factor-kappa B, inducible nitric oxide synthase, β-catenin, proliferating cell nuclear antigen, mucin-1, and significantly lower caveolin-1 and mucin-2 protein levels were shown in βERKO mice compared to WT mice. These data suggested a possible anti-inflammatory and anti-neoplastic mechanism of action of ERβ in CAC. These results demonstrate for the first time that ERβ provides protection in the AOM/DSS-induced CAC model in mice, suggesting a preventive and/or therapeutic potential for the use of ERβ-selective agonists in IBD.
Estrogen receptor-beta; azoxymethane; dextran sodium sulfate; inflammatory bowel disease; colon cancer
The purpose of this preliminary study was to determine if a course of chiropractic care would change blood pressure measurements in African American patients and to determine if a study was feasible in a chiropractic teaching clinic.
Twenty-four African American patients received chiropractic care in a chiropractic teaching clinic over a study period that spanned 23 visits for each patient. Inclusion criteria consisted of patients having a diagnosis of prehypertension (120-139/80-89) or hypertension stage 1 (140-159/90-99). The mean values of 3 baseline blood pressure readings were compared with the mean values of blood pressure readings taken on visits 21, 22, and 23.
For the entire sample, reductions for both systolic and diastolic blood pressures were not statistically significant (P > .07). When 4 patients having body mass index values that were considered as outliers were excluded, a statistically significant decrease in diastolic blood pressure was observed (P = .004). By group, a statistically significant reduction occurred in the hypertension stage 1 group for systolic and diastolic blood pressures.
This study showed that research of this nature may be feasible in chiropractic teaching clinics. The preliminary findings of this study showed that, for a subgroup of African American patients receiving chiropractic care, blood pressure decreased for (a) hypertension stage 1 patients and (b) the sample when those with excessive body mass index were excluded.
Blood pressure; Chiropractic; Health occupations students
The genus Capsicum is New World in origin and represents a complex of a wide variety of both wild and domesticated taxa. Peppers or fruits of Capsicum species rarely have been identified in the paleoethnobotanical record in either Meso- or South America. We report here confirmation of Capsicum sp. residues from pottery samples excavated at Chiapa de Corzo in southern Mexico dated from Middle to Late Preclassic periods (400 BCE to 300 CE). Residues from 13 different pottery types were collected and extracted using standard techniques. Presence of Capsicum was confirmed by ultra-performance liquid chromatography (UPLC)/MS-MS Analysis. Five pottery types exhibited chemical peaks for Capsicum when compared to the standard (dihydrocapsaicin). No peaks were observed in the remaining eight samples. Results of the chemical extractions provide conclusive evidence for Capsicum use at Chiapas de Corzo during a 700 year period (400 BCE–300 CE). Presence of Capsicum in different types of culinary-associated pottery raises questions how chili pepper could have been used during this early time period. As Pre-Columbian cacao products sometimes were flavored using Capsicum, the same pottery sample set was tested for evidence of cacao using a theobromine marker: these results were negative. As each vessel that tested positive for Capsicum had a culinary use we suggest here the possibility that chili residues from the Chiapas de Corzo pottery samples reflect either paste or beverage preparations for religious, festival, or every day culinary use. Alternatively, some vessels that tested positive merely could have been used to store peppers. Most interesting from an archaeological context was the presence of Capsicum residue obtained from a spouted jar, a pottery type previously thought only to be used for pouring liquids.
Epidermal growth factor receptors (EGFR) contribute to colonic tumorigenesis in experimental models of colon cancer. We previously showed that EGFR was also required for colonic tumor promotion by Western diet. The goal of this study was to identify EGFR-regulated microRNAs that contribute to diet-promoted colonic tumorigenesis.
Murine colonic tumors from Egfrwt and hypomorphic Egfrwa2 mice were screened using miRNA arrays and miR-143 and miR-145 changes confirmed by Northern, real time PCR and in situ analysis. Rodent and human sporadic and ulcerative colitis-associated colon cancers were examined for miR-143 and miR-145. Effects of EGFR on miR-143 and miR-145 expression were assessed in murine and human colonic cells and their putative targets examined in vitro and in vivo.
miR-143-and miR-145 were readily detected in normal colonocytes and comparable in Egfrwt and Egfrwa2 mice. These miRNAs were down-regulated in azoxymethane and inflammation-associated colonic tumors from Egfrwt mice, but up-regulated in Egfrwa2 tumors. They were also reduced in human sporadic and ulcerative colitis colon cancers. EGFR signals suppressed miR-143 and miR-145 in human and murine colonic cells. Transfected miR-143 and miR-145 inhibited HCT116 cell growth in vitro and in vivo and down-regulated G1 regulators, K-Ras, MYC, CCND2, cdk6 and E2F3, putative or established targets of these miRNAs. miRNA targets, Ras and MYC were increased in colonic tumors from Egfrwt, but not Egfrwa2 mice fed a Western diet.
EGFR suppresses miR-143 and miR-145 in murine models of colon cancer. Furthermore, Western diet unmasks the tumor suppressor roles of these EGFR-regulated miRNAs.
epidermal growth factor receptor; microRNA; cell cycle; azoxymethane; ulcerative colitis; Min mouse
136 glasses from the ninth-century monastery of San Vincenzo and its workshops have been analysed by electron microprobe in order to situate the assemblage within the first millennium CE glass making tradition. The majority of the glass compositions can be paralleled by Roman glass from the first to third centuries, with very few samples consistent with later compositional groups. Colours for trailed decoration on vessels, for vessel bodies and for sheet glass for windows were largely produced by melting the glass tesserae from old Roman mosaics. Some weakly-coloured transparent glass was obtained by re-melting Roman window glass, while some was produced by melting and mixing of tesserae, excluding the strongly coloured cobalt blues. Our data suggest that to feed the needs of the glass workshop, the bulk of the glass was removed as tesserae and windows from a large Roman building. This is consistent with a historical account according to which the granite columns of the monastic church were spolia from a Roman temple in the region. The purported shortage of natron from Egypt does not appear to explain the dependency of San Vincenzo on old Roman glass. Rather, the absence of contemporary primary glass may reflect the downturn in long-distance trade in the later first millennium C.E., and the role of patronage in the “ritual economy” founded upon donations and gift-giving of the time.
An exaggerated response to emotional stimuli is one of several symptoms widely reported by veterans of the 1991 Persian Gulf War. Many have attributed these symptoms to post-war stress; others have attributed the symptoms to deployment-related exposures and associated damage to cholinergic, dopaminergic, and white matter systems. We collected event-related potential (ERP) data from 20 veterans meeting Haley criteria for Gulf War Syndromes 1–3 and from 8 matched Gulf War veteran controls, who were deployed but not symptomatic, while they performed an auditory three-condition oddball task with gunshot and lion roar sounds as the distractor stimuli. Reports of hyperarousal from the ill veterans were significantly greater than those from the control veterans; different ERP profiles emerged to account for their hyperarousability. Syndromes 2 and 3, who have previously shown brainstem abnormalities, show significantly stronger auditory P1 amplitudes, purported to indicate compromised cholinergic inhibitory gating in the reticular activating system. Syndromes 1 and 2, who have previously shown basal ganglia dysfunction, show significantly weaker P3a response to distractor stimuli, purported to indicate dysfunction of the dopaminergic contribution to their ability to inhibit distraction by irrelevant stimuli. All three syndrome groups showed an attenuated P3b to target stimuli, which could be secondary to both cholinergic and dopaminergic contributions or disruption of white matter integrity.
Gulf War Illness; hyperarousal; ERPs; P1; P3a; P3b; cholinergic; dopaminergic
Colon cancer growth requires growth-promoting interactions between malignant colonocytes and stromal cells. Epidermal growth factor receptors (EGFR) are expressed on colonocytes and many stromal cells. Furthermore, EGFR is required for efficient tumorigenesis in experimental colon cancer models. To dissect the cell-specific role of EGFR, we manipulated receptor function on stromal cells and cancer cells. To assess the role of stromal EGFR, HCT116 human colon cancer cells were implanted into immunodeficient mice expressing dominant negative (DN) EgfrVelvet/+ or Egfr+/+. To assess the role of cancer cell EGFR, HCT116 transfectants expressing inducible DN-Egfr were implanted into immunodeficient mice. To dissect EGFR signals in vitro, we examined colon cancer cells in monoculture or in cocultures with fibroblasts for EGFR transactivation and prostaglandin synthase 2 (PTGS2) induction. EGFR signals were determined by blotting, immunostaining and real-time PCR. Tumor xenografts in EgfrVelvet/+ mice were significantly smaller than tumors in Egfr+/+ mice, with decreased proliferation (Ki67) and increased apoptosis (cleaved caspase-3) in cancer cells and decreased stromal blood vessels. Mouse stromal transforming growth factor alpha (TGFA), amphiregulin (AREG), PTGS2 and Il1b and interleukin-1 receptor 1 (Il1r1) transcripts and cancer cell beta catenin (CTNNB1) and cyclin D1 (CCND1) were significantly lower in tumors obtained from EgfrVelvet/+ mice. DN-EGFR HCT116 transfectants also formed significantly smaller tumors with reduced mouse Areg, Ptgs2, Il1b and Il1r1 transcripts. Coculture increased Caco-2 phospho-active ERBB (pERBB2), whereas DN-EGFR in Caco-2 cells suppressed fibroblast PTGS2 and prostaglandin E2 (PGE2). In monoculture, interleukin 1 beta (IL1B) transactivated EGFR in HCT116 cells. Stromal cell and colonocyte EGFRs are required for robust EGFR signals and efficient tumor growth, which involve EGFR–interleukin-1 crosstalk.
New megafossil and microfossil data indicate four episodes in the diversification of Silurian–Early Carboniferous land plants of South China, a relatively continuous regional record. Plant diversity increased throughout, but the rising curve was punctuated by three major falls. There were peaks of origination in the Ludlow–Pragian, Givetian, late Famennian and Visean and peaks of extinction in the Pragian–Emsian, Givetian and early Tournaisian. Speciation and extinction rates were highest in the Lochkovian–Pragian and became progressively lower in subsequent stages. High correlation coefficients indicate that these events are associated with the availability of land habitat contingent on eustatic variations and increasing numbers of cosmopolitan genera. Meanwhile, proportions of endemic genera declined gradually. Due to less endemism and more migrations, both speciation and species extinction rates reduced. The changes of diversity and the timing of the three extinctions of land plants in South China are similar to those known already from Laurussia. However, the largest events in the Lochkovian–Pragian and subsequent smaller ones have not been seen in the global pattern of plant evolution. These land plant events do not correspond well temporally with those affecting land vertebrates or marine invertebrates. In South China, the diversity curve of land plants is generally opposite to that of marine faunas, showing a strong effect of eustatic variations. The increasing diversity of both land vertebrates and plants was punctuated above the Devonian–Carboniferous boundary, known as Romer's Gap, implying common underlying constraints on macroevolution of land animals and plants.
Domestication can influence many functional traits in plants, from overall life-history and growth form to wood density and cell wall ultrastructure. Such changes can increase fitness of the domesticate in agricultural environments but may negatively affect survival in the wild. We studied effects of domestication on stem biomechanics in manioc by comparing domesticated and ancestral wild taxa from two different regions of greater Amazonia. We compared mechanical properties, tissue organisation and wood characteristics including microfibril angles in both wild and domesticated plants, each growing in two different habitats (forest or savannah) and varying in growth form (shrub or liana). Wild taxa grew as shrubs in open savannah but as lianas in overgrown and forested habitats. Growth form plasticity was retained in domesticated manioc. However, stems of the domesticate showed brittle failure. Wild plants differed in mechanical architecture between shrub and liana phenotypes, a difference that diminished between shrubs and lianas of the domesticate. Stems of wild plants were generally stiffer, failed at higher bending stresses and were less prone to brittle fracture compared with shrub and liana phenotypes of the domesticate. Biomechanical differences between stems of wild and domesticated plants were mainly due to changes in wood density and cellulose microfibril angle rather than changes in secondary growth or tissue geometry. Domestication did not significantly modify “large-scale” trait development or growth form plasticity, since both wild and domesticated manioc can develop as shrubs or lianas. However, “finer-scale” developmental traits crucial to mechanical stability and thus ecological success of the plant were significantly modified. This profoundly influenced the likelihood of brittle failure, particularly in long climbing stems, thereby also influencing the survival of the domesticate in natural situations vulnerable to mechanical perturbation. We discuss the different selective pressures that could explain evolutionary modifications of stem biomechanical properties under domestication in manioc.
Inflammatory bowel disease (IBD) is characterized by an injured epithelium. Development of agents that could enhance mucosal healing is a major goal in IBD therapeutics. The 18-kDa antrum mucosal protein (AMP-18) and a 21-mer peptide derived from AMP-18, stimulate accumulation of tight junction (TJ) proteins in cultured epithelial cells and mouse colonic mucosa to protect the mucosal barrier, suggesting it might be a useful agent to treat IBD.
We searched for molecular mechanisms by which AMP peptide or recombinant AMP-18 act on TJs in intact cell monolayers, or those disrupted by low-calcium medium. Roles of the p38 mitogen activated protein kinase (MAPK)/heat shock protein (hsp)25 pathway and PKCζ were investigated by immunoblotting and confocal microscopy.
AMP peptide activated p38 MAPK, which subsequently phosphorylated hsp25. Accumulated phospho-hsp25 was associated with perijunctional actin. AMP-18 also induced rapid phosphorylation of PKCζ and its colocalization with perijunctional actin in Caco2/bbe cells, which was accompanied by translocation and formation of complexes of “polarity proteins” in the TJ-containing detergent-insoluble fraction. Treatment with AMP-18 also stimulated accumulation of ZO-1, ZO-2, and JAM-A in nascent TJs known to associate with the multimeric p-PKCζ/Par6/ Cdc42/ECT2·GTP/Par3 polarity protein complex.
AMP-18 facilitates translocation and assembly of multiple proteins into TJs and their association with and subsequent stabilization of the actin filament network. We speculate that improved barrier function induced by AMP-18 is mediated by enhanced TJ assembly. Thus, AMP-18 may provide a promising lead to develop agents effective in healing injured colonic epithelium in IBD.
Antrum Mucosal Protein (AMP)-18; IBD; Tight Junctions; p38 mitogen activated protein kinase; PKCζ
One model for neurological assessment in chiropractic pertains to autonomic variability, tested commonly with heart rate variability (HRV). Since HRV may not be convenient to use on all patient visits, more user-friendly methods may help fill-in the gaps. Accordingly, this study tests the association between manual pulse rate and heart rate variability. The manual rates were also compared to the heart rate derived from HRV.
Forty-eight chiropractic students were examined with heart rate variability (SDNN and mean heart rate) and two manual radial pulse rate measurements. Inclusion criteria consisted of participants being chiropractic students. Exclusion criteria for 46 of the participants consisted of a body mass index being greater than 30, age greater than 35, and history of: a) dizziness upon standing, b) treatment of psychiatric disorders, and c) diabetes. No exclusion criteria were applied to the remaining two participants who were also convenience sample volunteers. Linear associations between the manual pulse rate methods and the two heart rate variability measures (SDNN and mean heart) were tested with Pearson’s correlation and simple linear regression.
Moderate strength inverse (expected) correlations were observed between both manual pulse rate methods and SDNN (r = −0.640, 95% CI −0.781, −0.435; r = −0.632, 95% CI −0.776, −0.425). Strong direct (expected) relationships were observed between the manual pulse rate methods and heart rate derived from HRV technology (r = 0.934, 95% CI 0.885, 0.962; r = 0.941, 95% CI 0.897, 0.966).
Manual pulse rates may be a useful option for assessing autonomic variability. Furthermore, this study showed a strong relationship between manual pulse rates and heart rate derived from HRV technology.
heart rate; chiropractic; pulse rate; adjustment; manipulation; fréquence cardiaque; rythme cardiaque; chiropratique; pouls; ajustement; manipulation
We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region’s past and offers a new context within which the late Holocene “Earthmovers” of the Llanos de Moxos could have emerged.
Marriage is a significant event in life-course of individuals, and creates a system that characterizes societal and economic structures. Marital patterns and dynamics over the years have changed a lot, with decreasing proportions of marriage, increased levels of divorce and co-habitation in developing countries. Although, such changes have been reported in African societies including Namibia, they have largely remained unexplained.
Objectives and Methods
In this paper, we examined trends and patterns of marital status of women of marriageable age: 15 to 49 years, in Namibia using the 1992, 2000 and 2006 Demographic and Health Survey (DHS) data. Trends were established for selected demographic variables. Two binary logistic regression models for ever-married versus never married, and cohabitation versus married were fitted to establish factors associated with such nuptial systems. Further a multinomial logistic regression models, adjusted for bio-demographic and socio-economic variables, were fitted separately for each year, to establish determinants of type of union (never married, married and cohabitation).
Results and Conclusions
Findings indicate a general change away from marriage, with a shift in singulate mean age at marriage. Cohabitation was prevalent among those less than 30 years of age, the odds were higher in urban areas and increased since 1992. Be as it may marriage remained a persistent nuptiality pattern, and common among the less educated and employed, but lower odds in urban areas. Results from multinomial model suggest that marital status was associated with age at marriage, total children born, region, place of residence, education level and religion. We conclude that marital patterns have undergone significant transformation over the past two decades in Namibia, with a coexistence of traditional marriage framework with co-habitation, and sizeable proportion remaining unmarried to the late 30s. A shift in the singulate mean age is becoming distinctive in the Namibian society.
Trachoma, caused by ocular Chlamydia trachomatis infection, is the leading infectious cause of blindess, but its prevalence is now falling in many countries. As the prevalence falls, an increasing proportion of individuals with clinical signs of follicular trachoma (TF) is not infected with C. trachomatis. A recent study in Tanzania suggested that other bacteria may play a role in the persistence of these clinical signs.
We examined associations between clinical signs of TF and ocular colonization with four pathogens commonly found in the nasopharnyx, three years after the initiation of mass azithromycin distribution. Children aged 0 to 5 years were randomly selected from 16 Gambian communitites. Both eyes of each child were examined and graded for trachoma according to the World Health Organization (WHO) simplified system. Two swabs were taken from the right eye: one swab was processed for polymerase chain reaction (PCR) using the Amplicor test for detection of C. trachomatis DNA and the second swab was processed by routine bacteriology to assay for the presence of viable Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Prevalence of TF was 6.2% (96/1538) while prevalence of ocular C. trachomatis infection was 1.0% (16/1538). After adjustment, increased odds of TF were observed in the presence of C. trachomatis (OR = 10.4, 95%CI 1.32–81.2, p = 0.03), S. pneumoniae (OR = 2.14, 95%CI 1.03–4.44, p = 0.04) and H. influenzae (OR = 4.72, 95% CI 1.53–14.5, p = 0.01).
Clinical signs of TF can persist in communities even when ocular C. trachomatis infection has been controlled through mass azithromycin distribution. In these settings, TF may be associated with ocular colonization with bacteria commonly carried in the nasopharnyx. This may affect the interpretation of impact surveys and the determinations of thresholds for discontinuing mass drug administration.
Trachoma, the world's leading infectious cause of blindness, is caused by ocular infection with the bacterium Chlamydia trachomatis. In low-prevalence settings and following mass treatment campaigns, clinically active follicular trachoma (TF) can be found in the absence of C. trachomatis infection. We carried out this study to investigate associations between ocular carriage of non-chlamydial pathogens and a clinical diagnosis of TF following a mass treatment campaign in The Gambia. We found that children who carried Streptococcus pneumoniae or Haemophilus influenza in their eyes were more likely to have been diagnosed with TF than children who did not carry these pathogens. In The Gambia, non-chlamydial pathogens may be inducing or exacerbating TF in the absence of C. trachomatis infection.
When attempting to estimate the impacts of future climate change it is important to reflect on information gathered during the past. Understanding historical trends may also aid in the assessment of likely future agricultural and horticultural changes. The timing of agricultural activities, such as grape harvest dates, is known to be influenced by climate and weather. However, fewer studies have been carried out on grapevine yield and quality. In this paper an analysis is undertaken of long-term data from the period 1805–2010 on grapevine yield (hl/ha) and must sugar content (°Oe) and their relation to temperature. Monthly mean temperatures were obtained for the same time period. Multiple regression was used to relate the viticulture variables to temperature, and long-term trends were calculated. Overall, the observed trends over time are compatible with results from other long term studies. The findings confirm a relationship between yield, must sugar content and temperature data; increased temperatures were associated with higher yields and higher must sugar content. However, the potential increase in yield is currently limited by legislation, while must sugar content is likely to further increase with rising temperatures.
Pre-Pottery Neolithic assemblages are best known from the fertile areas of the Mediterranean Levant. The archaeological site of Jebel Qattar 101 (JQ-101), at Jubbah in the southern part of the Nefud Desert of northern Saudi Arabia, contains a large collection of stone tools, adjacent to an Early Holocene palaeolake. The stone tool assemblage contains lithic types, including El-Khiam and Helwan projectile points, which are similar to those recorded in Pre-Pottery Neolithic A and Pre-Pottery Neolithic B assemblages in the Fertile Crescent. Jebel Qattar lies ∼500 kilometres outside the previously identified geographic range of Pre-Pottery Neolithic cultures. Technological analysis of the typologically diagnostic Jebel Qattar 101 projectile points indicates a unique strategy to manufacture the final forms, thereby raising the possibility of either direct migration of Levantine groups or the acculturation of mobile communities in Arabia. The discovery of the Early Holocene site of Jebel Qattar suggests that our view of the geographic distribution and character of Pre-Pottery Neolithic cultures may be in need of revision.
Several studies have shown that global crop production needs to double by 2050 to meet the projected demands from rising population, diet shifts, and increasing biofuels consumption. Boosting crop yields to meet these rising demands, rather than clearing more land for agriculture has been highlighted as a preferred solution to meet this goal. However, we first need to understand how crop yields are changing globally, and whether we are on track to double production by 2050. Using ∼2.5 million agricultural statistics, collected for ∼13,500 political units across the world, we track four key global crops—maize, rice, wheat, and soybean—that currently produce nearly two-thirds of global agricultural calories. We find that yields in these top four crops are increasing at 1.6%, 1.0%, 0.9%, and 1.3% per year, non-compounding rates, respectively, which is less than the 2.4% per year rate required to double global production by 2050. At these rates global production in these crops would increase by ∼67%, ∼42%, ∼38%, and ∼55%, respectively, which is far below what is needed to meet projected demands in 2050. We present detailed maps to identify where rates must be increased to boost crop production and meet rising demands.
The Campanian Ignimbrite (CI) volcanic eruption was the most explosive in Europe in the last 200,000 years. The event coincided with the onset of an extremely cold climatic phase known as Heinrich Event 4 (HE4) approximately 40,000 years ago. Their combined effect may have exacerbated the severity of the climate through positive feedbacks across Europe and possibly globally. The CI event is of particular interest not only to investigate the role of volcanism on climate forcing and palaeoenvironments, but also because its timing coincides with the arrival into Europe of anatomically modern humans, the demise of Neanderthals, and an associated major shift in lithic technology. At this stage, however, the degree of interaction between these factors is poorly known, based on fragmentary and widely dispersed data points. In this study we provide important new data from Eastern Europe which indicate that the magnitude of the CI eruption and impact of associated distal ash (tephra) deposits may have been substantially greater than existing models suggest. The scale of the eruption is modelled by tephra distribution and thickness, supported by local data points. CI ashfall extends as far as the Russian Plain, Eastern Mediterranean and northern Africa. However, modelling input is limited by very few data points in Eastern Europe. Here we investigate an unexpectedly thick CI tephra deposit in the southeast Romanian loess steppe, positively identified using geochemical and geochronological analyses. We establish the tephra as a widespread primary deposit, which blanketed the topography both thickly and rapidly, with potentially catastrophic impacts on local ecosystems. Our discovery not only highlights the need to reassess models for the magnitude of the eruption and its role in climatic transition, but also suggests that it may have substantially influenced hominin population and subsistence dynamics in a region strategic for human migration into Europe.
The World Health Organization has recommended three rounds of mass drug administration (MDA) with antibiotics in districts where the prevalence of follicular trachoma (TF) is ≥10% in children aged 1–9 years, with treatment coverage of at least 80%. For districts at 5–10% TF prevalence it was recommended that TF be assessed in 1–9 year olds in each community within the district, with three rounds of MDA provided to any community where TF≥10%. Worldwide, over 40 million people live in districts whose TF prevalence is estimated to be between 5 and 10%. The best way to treat these districts, and the optimum role of testing for infection in deciding whether to initiate or discontinue MDA, are unknown.
In a community randomized trial with a factorial design, we randomly assigned 48 communities in four Gambian districts, in which the prevalence of trachoma was known or suspected to be above 10%, to receive annual mass treatment with expected coverage of 80–89% (“Standard”), or to receive an additional visit in an attempt to achieve coverage of 90% or more (“Enhanced”). The same 48 communities were randomised to receive mass treatment annually for three years (“3×”), or to have treatment discontinued if Chlamydia trachomatis (Ct) infection was not detected in a sample of children in the community after mass treatment (stopping rule(“SR”)). Primary outcomes were the prevalence of TF and of Ct infection in 0–5 year olds at 36 months.
The baseline prevalence of TF and of Ct infection in the target communities was 6.5% and 0.8% respectively. At 36 months the prevalence of TF was 2.8%, and that of Ct infection was 0.5%. No differences were found between the arms in TF or Ct infection prevalence either at baseline (Standard-3×: TF 5.6%, Ct 0.7%; Standard-SR: TF 6.1%, Ct 0.2%; Enhanced-3×: TF 7.4%, Ct 0.9%; and Enhanced-SR: TF 6.2%, Ct 1.2%); or at 36 months (Standard-3×: TF 2.3%, Ct 1.0%; Standard-SR TF 2.5%, Ct 0.2%; Enhanced-3× TF 3.0%, Ct 0.2%; and Enhanced-SR TF 3.2%, Ct 0.7% ). The implementation of the stopping rule led to treatment stopping after one round of MDA in all communities in both SR arms. Mean treatment coverage of children aged 0–9 in communities randomised to standard treatment was 87.7% at baseline and 84.8% and 88.8% at one and two years, respectively. Mean coverage of children in communities randomized to enhanced treatment was 90.0% at baseline and 94.2% and 93.8% at one and two years, respectively. There was no evidence of any difference in TF or Ct prevalence at 36 months resulting from enhanced coverage or from one round of MDA compared to three.
The Gambia is close to the elimination target for active trachoma. In districts prioritised for three MDA rounds, one round of MDA reduced active trachoma to low levels and Ct infection was not detectable in any community. There was no additional benefit to giving two further rounds of MDA. Programmes could save scarce resources by determining when to initiate or to discontinue MDA based on testing for Ct infection, and one round of MDA may be all that is necessary in some settings to reduce TF below the elimination threshold.
Trachoma, which results from infection with a bacterium Chlamydia trachomatis(Ct), is a leading cause of preventable blindness in the world. One of the currently used control methods is mass drug administration (MDA) with azithromycin, which is initiated according to rates of follicular trachoma(TF) in children. This study was a clinical trial done to determine whether testing communities for Ct infection will prevent unnecessary rounds of MDA. This was done by allowing communities to stop treatment if their infection had been reduced below a threshold. The study compared the effects of one round of mass treatment to three and found that there was no difference in either follicular trachoma or infection rates after three years. One round of treatment reduced TF to a low level. Tests for infection could be used to decide when to start or discontinue MDA and to prevent unnecessary treatment rounds in settings like The Gambia.
This theoretical report gives an example for how coefficient of variation (CV) and quartile analysis (QA) to assess outliers might be able to be used to analyze numeric data in practice for an individual patient.
A patient was examined for 8 visits using infrared instrumentation for measurement of mastoid fossa temperature differential (MFTD) readings. The CV and QA were applied to the readings. The participant also completed the Short Form–12 health perception survey on each visit, and these findings were correlated with CV to determine if CV had outcomes support (clinical significance).
An outlier MFTD reading was observed on the eighth visit according to QA that coincided with the largest CV value for the MFTDs. Correlations between the Short Form–12 and CV were low to negligible, positive, and statistically nonsignificant.
This case provides an example of how basic statistical analyses could possibly be applied to numerical data in chiropractic practice for an individual patient. This might add objectivity to analyzing an individual patient's data in practice, particularly if clinical significance of a clinical numerical finding is unknown.
Biostatistics; Outcome assessment; Thermography; Chiropractic
As concentration (dose) of health care providers increases, health outcomes (responses) are expected to be favorable (e.g., decrease in mortality rates). Accordingly, this data-driven, ecological study compares hypertension mortality rates in the U.S. by state to concentrations of doctors of chiropractic (DC) and medical doctors (MD). DC and MD concentrations (per 10,000 population) were separately compared to 2008 hypertension death rates using Spearman correlation analysis and linear regression (where appropriate). DC concentrations revealed a stronger beneficial association with hypertension death rates (r = −0.430, p = 0.0020) compared to MD concentrations (r = −0.029 with an observed outlier, and r = −0.085 without the outlier; both coefficients not statistically significant). Linear regression revealed that an average national decrease of approximately one hypertension death per 100,000 population (95% CI = −1.4 to −0.4) would be expected with an increase of one DC per 10,000 population within the range in this study (1.0 to 5.2 DCs per 10,000 population). Since this is an observational study, causal inference is not claimed. The study is intended as a first step to research having other designs such as case-control.
Physician; chiropractic; hypertension; mortality
The first objective of this study is to examine temporal patterns in ancient dog burials in the Lake Baikal region of Eastern Siberia. The second objective is to determine if the practice of dog burial here can be correlated with patterns in human subsistence practices, in particular a reliance on terrestrial mammals. Direct radiocarbon dating of a suite of the region’s dog remains indicates that these animals were given burial only during periods in which human burials were common. Dog burials of any kind were most common during the Early Neolithic (∼7–8000 B.P.), and rare during all other time periods. Further, only foraging groups seem to have buried canids in this region, as pastoralist habitation sites and cemeteries generally lack dog interments, with the exception of sacrificed animals. Stable carbon and nitrogen isotope data indicate that dogs were only buried where and when human diets were relatively rich in aquatic foods, which here most likely included river and lake fish and Baikal seal (Phoca sibirica). Generally, human and dog diets appear to have been similar across the study subregions, and this is important for interpreting their radiocarbon dates, and comparing them to those obtained on the region’s human remains, both of which likely carry a freshwater old carbon bias. Slight offsets were observed in the isotope values of dogs and humans in our samples, particularly where both have diets rich in aquatic fauna. This may result from dietary differences between people and their dogs, perhaps due to consuming fish of different sizes, or even different tissues from the same aquatic fauna. This paper also provides a first glimpse of the DNA of ancient canids in Northeast Asia.
Direct evidence of the environmental impact of human colonization and subsequent human adaptational responses to new environments is extremely rare anywhere in the world. New Zealand was the last Polynesian island group to be settled by humans, who arrived around the end of the 13th century AD. Little is known about the nature of human adaptation and mobility during the initial phase of colonization. We report the results of the isotopic analysis (carbon, nitrogen and strontium) of the oldest prehistoric skeletons discovered in New Zealand to assess diet and migration patterns. The isotope data show that the culturally distinctive burials, Group 1, had similar diets and childhood origins, supporting the assertion that this group was distinct from Group 2/3 and may have been part of the initial colonizing population at the site. The Group 2/3 individuals displayed highly variable diets and likely lived in different regions of the country before their burial at Wairau Bar, supporting the archaeological evidence that people were highly mobile in New Zealand since the initial phase of human settlement.
The reefs surrounding the Gilbert Islands (Republic of Kiribati, Central Pacific), like many throughout the world, have undergone a period of rapid and intensive environmental perturbation over the past 100 years. A byproduct of this perturbation has been a reduction of the number of shark species present in their waters, even though sharks play an important in the economy and culture of the Gilbertese. Here we examine how shark communities changed over time periods that predate the written record in order to understand the magnitude of ecosystem changes in the Central Pacific. Using a novel data source, the shark tooth weapons of the Gilbertese Islanders housed in natural history museums, we show that two species of shark, the Spot-tail (Carcharhinus sorrah) and the Dusky (C. obscurus), were present in the islands during the last half of the 19th century but not reported in any historical literature or contemporary ichthyological surveys of the region. Given the importance of these species to the ecology of the Gilbert Island reefs and to the culture of the Gilbertese people, documenting these shifts in baseline fauna represents an important step toward restoring the vivid splendor of both ecological and cultural diversity.