Additions and Corrections to David S. Spear, The Personnel of the Norman Cathedrals during the Ducal Period, 911-1204 (London: Institute of Historical Research, 2006)

I am grateful to have this opportunity to share updates to my book with a wide audience. Since its publication, now eight years on, I have been able to add a good number of additional references and to correct some errors. This article also brings the reader up to date on recent bibliography in the field. Several works have been published by two authors in particular – Richard Allen and Jörg Peltzer – which have added greatly to our knowledge of..

Autophagic Flux Modulation by Wnt/β-Catenin Pathway Inhibition in Hepatocellular Carcinoma

Autophagy targets cellular components for lysosomal-dependent degradation in which the products of degradation may be recycled for protein synthesis and utilized for energy production. Autophagy also plays a critical role in cell homeostasis and the regulation of many physiological and pathological processes and prompts this investigation of new agents to effect abnormal autophagy in hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is a synthetic inhibitor of the Wnt/β-catenin pathway that exhibits anti-proliferative and anti-angiogenic effects on different types of cancer cells. The combination of FH535 with sorafenib promotes a synergistic inhibition of HCC and liver cancer stem cell proliferation, mediated in part by the simultaneous disruption of mitochondrial respiration and glycolysis. We demonstrated that FH535 decreased HCC tumor progression in a mouse xenograft model. For the first time, we showed the inhibitory effect of an FH535 derivative, FH535-N, alone and in combination with sorafenib on HCC cell proliferation. Our study revealed the contributing effect of Wnt/β-catenin pathway inhibition by FH535 and its derivative (FH535-N) through disruption of the autophagic flux in HCC cells

Preliminary genetic evidence of two different populations of Opisthorchis viverrini in Lao PDR

Opisthorchis viverrini is a major public health concern in Southeast Asia. Various reports have suggested that this parasite may represent a species complex, with genetic structure in the region perhaps being dictated by geographical factors and different species of intermediate hosts. We used four microsatellite loci to analyze O. viverrini adult worms originating from six species of cyprinid fish in Thailand and Lao PDR. Two distinct O. viverrini populations were observed. In Ban Phai, Thailand, only one subgroup occurred, hosted by two different fish species. Both subgroups occurred in fish from That Luang, Lao PDR, but were represented to very different degrees among the fish hosts there. Our data suggest that, although geographical separation is more important than fish host specificity in influencing genetic structure, it is possible that two species of Opisthorchis, with little interbreeding, are present near Vientiane in Lao PDR

A case study of Kanban implementation within the Pharmaceutical Supply Chain

The paper explores the implementation of the kanban system, which is a Lean technique, within the Pharmaceutical Supply Chain (PSC). The case study provides insight to the benefits and challenges arising from the application of this technique, within a group of cooperative pharmacists, in Greece. The research questions developed from the review of the literature were tested using evidence from field-based, action research within a pharmaceutical organisation. The reported case study contributes to the longer term debate on assessing the Lean maturity level within the healthcare sector. There are two primary findings: i) that the adoption of kanban system provides a strategic benefit and improves the quality of services. ii) it also provides a basis for a strategy of operational change; it gives the opportunity to the organisation to move away from the current push delivery and logistics systems toward improved logistics strategy models

Training in childhood obesity management in the United States: a survey of pediatric, internal medicine-pediatrics and family medicine residency program directors

<p>Abstract</p> <p>Background</p> <p>Information about the availability and effectiveness of childhood obesity training during residency is limited.</p> <p>Methods</p> <p>We surveyed residency program directors from pediatric, internal medicine-pediatrics (IM-Peds), and family medicine residency programs between September 2007 and January 2008 about childhood obesity training offered in their programs.</p> <p>Results</p> <p>The response rate was 42.2% (299/709) and ranged by specialty from 40.1% to 45.4%. Overall, 52.5% of respondents felt that childhood obesity training in residency was extremely important, and the majority of programs offered training in aspects of childhood obesity management including prevention (N = 240, 80.3%), diagnosis (N = 282, 94.3%), diagnosis of complications (N = 249, 83.3%), and treatment (N = 242, 80.9%). However, only 18.1% (N = 54) of programs had a formal childhood obesity curriculum with variability across specialties. Specifically, 35.5% of IM-Peds programs had a formal curriculum compared to only 22.6% of pediatric and 13.9% of family medicine programs (p < 0.01). Didactic instruction was the most commonly used training method but was rated as only somewhat effective by 67.9% of respondents using this method. The most frequently cited significant barrier to implementing childhood obesity training was competing curricular demands (58.5%).</p> <p>Conclusions</p> <p>While most residents receive training in aspects of childhood obesity management, deficits may exist in training quality with a minority of programs offering a formal childhood obesity curriculum. Given the high prevalence of childhood obesity, a greater emphasis should be placed on development and use of effective training strategies suitable for all specialties training physicians to care for children.</p

Deep Sequencing of the Vaginal Microbiota of Women with HIV

BACKGROUND: Women living with HIV and co-infected with bacterial vaginosis (BV) are at higher risk for transmitting HIV to a partner or newborn. It is poorly understood which bacterial communities constitute BV or the normal vaginal microbiota among this population and how the microbiota associated with BV responds to antibiotic treatment. METHODS AND FINDINGS: The vaginal microbiota of 132 HIV positive Tanzanian women, including 39 who received metronidazole treatment for BV, were profiled using Illumina to sequence the V6 region of the 16S rRNA gene. Of note, Gardnerella vaginalis and Lactobacillus iners were detected in each sample constituting core members of the vaginal microbiota. Eight major clusters were detected with relatively uniform microbiota compositions. Two clusters dominated by L. iners or L. crispatus were strongly associated with a normal microbiota. The L. crispatus dominated microbiota were associated with low pH, but when L. crispatus was not present, a large fraction of L. iners was required to predict a low pH. Four clusters were strongly associated with BV, and were dominated by Prevotella bivia, Lachnospiraceae, or a mixture of different species. Metronidazole treatment reduced the microbial diversity and perturbed the BV-associated microbiota, but rarely resulted in the establishment of a lactobacilli-dominated microbiota. CONCLUSIONS: Illumina based microbial profiling enabled high though-put analyses of microbial samples at a high phylogenetic resolution. The vaginal microbiota among women living with HIV in Sub-Saharan Africa constitutes several profiles associated with a normal microbiota or BV. Recurrence of BV frequently constitutes a different BV-associated profile than before antibiotic treatment

Managing Oil Palm Plantations More Sustainably: Large-Scale Experiments Within the Biodiversity and Ecosystem Function in Tropical Agriculture (BEFTA) Programme

Conversion of tropical forest to agriculture results in reduced habitat heterogeneity, and associated declines in biodiversity and ecosystem functions. Management strategies to increase biodiversity in agricultural landscapes have therefore often focused on increasing habitat complexity; however, the large-scale, long-term ecological experiments that are needed to test the effects of these strategies are rare in tropical systems. Oil palm (Elaeis guineensis Jacq.)—one of the most widespread and important tropical crops—offers substantial potential for developing wildlife-friendly management strategies because of its long rotation cycles and tree-like structure. Although there is awareness of the need to increase sustainability, practical options for how best to manage oil palm plantations, for benefits to both the environment and crop productivity, have received little research attention. In this paper we introduce the Biodiversity and Ecosystem Function in Tropical Agriculture (BEFTA) Programme: a long-term research collaboration between academia and industry in Sumatra, Indonesia. The BEFTA Programme aims to better understand the oil palm agroecosystem and test sustainability strategies. We hypothesise that adjustments to oil palm management could increase structural complexity, stabilise microclimate, and reduce reliance on chemical inputs, thereby helping to improve levels of biodiversity and ecosystem functions. The Programme has established four major components: (1) assessing variability within the plantation under business-as-usual conditions; (2) the BEFTA Understory Vegetation Project, which tests the effects of varying herbicide regimes; (3) the Riparian Ecosystem Restoration in Tropical Agriculture (RERTA) Project, which tests strategies for restoring riparian habitat; and (4) support for additional collaborative projects within the Programme landscape. Across all projects, we are measuring environmental conditions, biodiversity, and ecosystem functions. We also measure oil palm yield and production costs, in order to assess whether suggested sustainability strategies are feasible from an agronomic perspective. Early results show that oil palm plantation habitat is more variable than might be expected from a monoculture crop, and that everyday vegetation management decisions have significant impacts on habitat structure. The BEFTA Programme highlights the value of large-scale collaborative projects for understanding tropical agricultural systems, and offers a highly valuable experimental set-up for improving our understanding of practices to manage oil palm more sustainably

Community Analysis of Chronic Wound Bacteria Using 16S rRNA Gene-Based Pyrosequencing: Impact of Diabetes and Antibiotics on Chronic Wound Microbiota

Background: Bacterial colonization is hypothesized to play a pathogenic role in the non-healing state of chronic wounds. We characterized wound bacteria from a cohort of chronic wound patients using a 16S rRNA gene-based pyrosequencing approach and assessed the impact of diabetes and antibiotics on chronic wound microbiota. Methodology/Principal Findings: We prospectively enrolled 24 patients at a referral wound center in Baltimore, MD; sampled patients' wounds by curette; cultured samples under aerobic and anaerobic conditions; and pyrosequenced the 16S rRNA V3 hypervariable region. The 16S rRNA gene-based analyses revealed an average of 10 different bacterial families in wounds-approximately 4 times more than estimated by culture-based analyses. Fastidious anaerobic bacteria belonging to the Clostridiales family XI were among the most prevalent bacteria identified exclusively by 16S rRNA gene-based analyses. Community-scale analyses showed that wound microbiota from antibiotic treated patients were significantly different from untreated patients (p = 0.007) and were characterized by increased Pseudomonadaceae abundance. These analyses also revealed that antibiotic use was associated with decreased Streptococcaceae among diabetics and that Streptococcaceae was more abundant among diabetics as compared to non-diabetics. Conclusions/Significance: The 16S rRNA gene-based analyses revealed complex bacterial communities including anaerobic bacteria that may play causative roles in the non-healing state of some chronic wounds. Our data suggest that antimicrobial therapy alters community structure-reducing some bacteria while selecting for others

Multiplex Immunoassay of Lower Genital Tract Mucosal Fluid from Women Attending an Urban STD Clinic Shows Broadly Increased IL1ß and Lactoferrin

BACKGROUND: More than one million new cases of sexually transmitted diseases (STDs) occur each day. The immune responses and inflammation induced by STDs and other frequent non-STD microbial colonizations (i.e. Candida and bacterial vaginosis) can have serious pathologic consequences in women including adverse pregnancy outcomes, infertility and increased susceptibility to infection by other pathogens. Understanding the types of immune mediators that are elicited in the lower genital tract by these infections/colonizations can give important insights into the innate and adaptive immune pathways that are activated and lead to strategies for preventing pathologic effects. METHODOLOGY/PRINCIPAL FINDINGS: 32 immune mediators were measured by multiplexed immunoassays to assess the immune environment of the lower genital tract mucosa in 84 women attending an urban STD clinic. IL-3, IL-1ß, VEGF, angiogenin, IL-8, ß2Defensin and ß3Defensin were detected in all subjects, Interferon-α was detected in none, while the remaining mediators were detected in 40% to 93% of subjects. Angiogenin, VEGF, FGF, IL-9, IL-7, lymphotoxin-α and IL-3 had not been previously reported in genital mucosal fluid from women. Strong correlations were observed between levels of TNF-α, IL-1ß and IL-6, between chemokines IP-10 and MIG and between myeloperoxidase, IL-8 and G-CSF. Samples from women with any STD/colonization had significantly higher levels of IL-8, IL-3, IL-7, IL-1ß, lactoferrin and myeloperoxidase. IL-1ß and lactoferrin were significantly increased in gonorrhea, Chlamydia, cervicitis, bacterial vaginosis and trichomoniasis. CONCLUSIONS/SIGNIFICANCE: These studies show that mucosal fluid in general appears to be an environment that is rich in immune mediators. Importantly, IL-1ß and lactoferrin are biomarkers for STDs/colonizations providing insights into immune responses and pathogenesis at this mucosal site