The Asia Minor Greek adpositional cycle: a tale of multiple causation

This paper examines the interplay of language-internal continuity and external influence in the cyclical development of the Asia Minor Greek adpositional system. The Modern Greek dialects of Asia Minor inherited an adpositional system of the Late Medieval Greek type whereby secondary adpositions regularly combined with primary adpositions to encode spatial region. Secondary adpositions could originally precede simple adpositions ([PREPOSITION + PREPOSITION + NPACC]) or follow the adpositional complement ([PREPOSITION + NPACC + POSTPOSITION]). Asia Minor Greek replicated the structure of Ottoman Turkish postpositional phrases to resolve this variability, fixing the position of secondary adpositions after the complement and thus developing circumpositions of the type [PREPOSITION + NPACC + POSTPOSITION]. Later, some varieties dropped the primary preposition SE from circumpositional phrases, leaving (secondary) postpositions as the only overt relator ([NPACC + POSTPOSITION]) in some environments. In addition, a number of Turkish postpositions were borrowed wholesale, thus enriching the Greek adpositional inventory.

Phospha-adamantane ligands and phosphorous ionic liquids for palladium-catalyzed cross-coupling reactions /

New and robust methodologies have been designed for palladiumcatalyzed cross-coupling reactions involving a library of novel tertiary phosphine ligands incorporating a phospha-adamantane framework. The secondary phosphine, l,3,5,7-tetramethyl-2,4,8-trioxa-6-phospha-adamantane was converted into a small library of tertiary phosphine derivatives and the ability of these tertiary phosphaadamantanes to act as effective ligands in the palladium-catalyzed amination reaction and p-alkyl-Suzuki cross-coupling was examined. l,3,5,7-Tetramethyl-6- phenyl-2,4,8-trioxa-6-phosphaadamantane (PA-Ph) used in combination with Pd2(dba)3 CHCI3 facilitated the reaction of an array of aryl iodides, bromides and chlorides with a variety secondary and primary amines to give tertiary and secondary amines respectively in good to excellent yields. 8-(2,4-Dimethoxyphenyl)- l,3,5,7-tetramethyl-2,4,6-trioxa-8-phospha-tricyclo[3.3.1.1*3,7*]decane used in combination with Pd(0Ac)2 permitted the reaction of an array of alkyl iodides, and bromides with a variety aryl boronic acids and alkyl 9-BBN compounds in good to excellent yields. Subsequent to this work, the use of phosphorous based ionic liquids, specifically tetradecyltrihexylphosphonium chloride (THPC), in the Heck reaction provided good to excellent yields in the coupling of aryl iodides and bromides with a variety of olefins.

Chemical composition of mineral phases of serpentinized and steatized peridotite from the Mid Atlantic Ridge (15°20'N Fracture Zone, ODP Leg209)

Serpentinization of abyssal peridotites is known to produce extremely reducing conditions as a result of dihydrogen (H2,aq) release upon oxidation of ferrous iron in primary phases to ferric iron in secondary minerals by H2O.We have compiled and evaluated thermodynamic data for Fe-Ni-Co-O-S phases and computed phase relations in fO2,g-fS2,g and aH2,aq-aH2S,aq diagrams for temperatures between 150 and 400°C at 50MPa.We use the relations and compositions of Fe-Ni-Co-O-S phases to trace changes in oxygen and sulfur fugacities during progressive serpentinization and steatitization of peridotites from the Mid-Atlantic Ridge in the 15°20'N Fracture Zone area (Ocean Drilling Program Leg 209). Petrographic observations suggest a systematic change from awaruite- magnetite-pentlandite and heazlewoodite-magnetite-pentlandite assemblages forming in the early stages of serpentinization to millerite-pyrite-polydymite-dominated assemblages in steatized rocks. Awaruite is observed in all brucite-bearing partly serpentinized rocks. Apparently, buffering of silica activities to low values by the presence of brucite facilitates the formation of large amounts of hydrogen, which leads to the formation of awaruite. Associated with the prominent desulfurization of pentlandite, sulfide is removed from the rock during the initial stage of serpentinization. In contrast, steatitization indicates increased silica activities and that highsulfur-fugacity sulfides, such as polydymite and pyrite-vaesite solid solution, form as the reducing capacity of the peridotite is exhausted and H2 activities drop. Under these conditions, sulfides will not desulfurize but precipitate and the sulfur content of the rock increases. The co-evolution of fO2,g-fS2,g in the system follows an isopotential of H2S,aq, indicating that H2S in vent fluids is buffered. In contrast, H2 in vent fluids is not buffered by Fe-Ni-Co-O-S phases, which merely monitor the evolution of H2 activities in the fluids in the course of progressive rock alteration.The co-occurrence of pentlandite- awaruite-magnetite indicates H2,aq activities in the interacting fluids near the stability limit of water. The presence of a hydrogen gas phase would add to the catalyzing capacity of awaruite and would facilitate the abiotic formation of organic compounds.

Analysis of Transmitted Resistance to Raltegravir and Selective Pressure among HIV-1-Infected Patients on a Failing HAART in Sao Paulo, Brazil

We studied the presence of primary resistance to raltegravir (RAL), natural polymorphisms, and selection pressure on HIV-1 integrase. We found a high frequency of integrase polymorphisms related to the resistance to RAL and sequence stability. Further studies are needed to determine the importance of these polymorphisms to RAL resistance.

Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance

BACKGROUND: All site-specific interactions between HIV type-1 (HIV-1) subtype, human leukocyte antigen (HLA)-associated immune selection and integrase inhibitor resistance are not completely understood. We examined naturally occurring polymorphisms in HIV-1 integrase sequences from 342 antiretroviral-naive individuals from the Western Australian HIV Cohort Study and the Swiss HIV Cohort Study. METHODS: Standard bulk sequencing and sequence-based typing were used to generate integrase sequences and high-resolution HLA genotypes, respectively. Viral residues were examined with respect to drug resistance mutations and CD8(+) T-cell escape mutations. RESULTS: In both predominantly subtype B cohorts, 12 of 38 sites that mediate integrase inhibitor resistance mutations were absolutely conserved, and these included the primary resistance mutations. There were 18 codons with non-primary drug resistance-associated substitutions at rates of up to 58.8% and eight sites with alternative polymorphisms. Five viral residues were potentially subject to dual-drug and HLA-associated immune selection in which both selective pressures either drove the same amino acid substitution (codons 72, 157 and 163) or HLA alleles were associated with an alternative polymorphism that would alter the genetic barrier to resistance (codons 125 and 193). The common polymorphism T125A, which was characteristic of non-subtype B and was also associated with carriage of HLA-B*57/*5801, increased the mutational barrier to the resistance mutation T125K. CONCLUSIONS: Primary integrase inhibitor resistance mutations were not detected in the absence of drug exposure in keeping with sites of high constraint. Viral polymorphisms caused by immune selection and/or associated with non-subtype B might alter the genetic barrier to some non-primary resistance-associated mutations.

Transition from primary to secondary school: Middle schooling concepts

After reading this chapter, you should be able to: • Identify the needs of early adolescents • Consider four key areas for supporting transitioning students (i.e., self, social, academic, and differentiation) • Identify resources that can help create successful transitioning programs • Understand ways to devise and facilitate transitioning programs

Identifying strategies to maximise recruitment and retention of practices and patients in a multicentre randomised controlled trial of an intervention to optimise secondary prevention for coronary heart disease in primary care.

Background Recruitment and retention of patients and healthcare providers in randomised controlled trials (RCTs) is important in order to determine the effectiveness of interventions. However, failure to achieve recruitment targets is common and reasons why a particular recruitment strategy works for one study and not another remain unclear. We sought to describe a strategy used in a multicentre RCT in primary care, to report researchers’ and participants’ experiences of its implementation and to inform future strategies to maximise recruitment and retention. Methods In total 48 general practices and 903 patients were recruited from three different areas of Ireland to a RCT of an intervention designed to optimise secondary prevention of coronary heart disease. The recruitment process involved telephoning practices, posting information, visiting practices, identifying potential participants, posting invitations and obtaining consent. Retention involved patients attending reviews and responding to questionnaires and practices facilitating data collection. Results We achieved high retention rates for practices (100%) and for patients (85%) over an 18-month intervention period. Pilot work, knowledge of the setting, awareness of change in staff and organisation amongst participant sites, rapid responses to queries and acknowledgement of practitioners’ contributions were identified as being important. Minor variations in protocol and research support helped to meet varied, complex and changing individual needs of practitioners and patients and encouraged retention in the trial. A collaborative relationship between researcher and practice staff which required time to develop was perceived as vital for both recruitment and retention. Conclusions Recruiting and retaining the numbers of practices and patients estimated as required to provide findings with adequate power contributes to increased confidence in the validity and generalisability of RCT results. A continuous dynamic process of monitoring progress within trials and tailoring strategies to particular circumstances, whilst not compromising trial protocols, should allow maximal recruitment and retention.

HIV-1 drug resistance transmission networks in southwest Switzerland.

To determine viral subtypes and resistance mutations to antiretroviral treatment (ART) in untreated HIV-1 acutely infected subjects from Southwest Switzerland. Clinical samples were obtained from the HIV primary infection cohort from Lausanne. Briefly, pol gene was amplified by nested PCR and sequenced to generate a 1?kb sequence spanning protease and reverse transcriptase key protein regions. Nucleotide sequences were used to assess viral genotype and ART resistance mutations. Blood specimens and medical information were obtained from 30 patients. Main viral subtypes corresponded to clade B, CRF02_AG, and F1. Resistant mutations to PIs consisted of L10V and accessory mutations 16E and 60E present in all F1 clades. The NNRTI major resistant mutation 103N was detected in all F1 viruses and in other 2 clades. Additionally, we identified F1 sequences from other 6 HIV infected and untreated individuals from Southwest Switzerland, harboring nucleotide motifs and resistance mutations to ART as observed in the F1 strains from the cohort. These data reveal a high transmission rate (16.6%) for NNRTI resistant mutation 103N in a cohort of HIV acute infection. Three of the 5 resistant strains were F1 clades closely related to other F1 isolates from HIV-1 infection untreated patients also coming from Southwest Switzerland. Overall, we provide strong evidence towards an HIV-1 resistant transmission network in Southwest Switzerland. These findings have relevant implications for the local molecular mapping of HIV-1 and future ART surveillance studies in the region.

Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection

BACKGROUND The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants. METHODS Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth. RESULTS A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two-and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P < 0.001 for both comparisons with the other groups). CONCLUSIONS In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two-or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population.

Case-control study of factors associated with virologic failure in HIV-infected children on HAART in Botswana, a developing African country

According to the United Nations Program on HIV/AIDS (UNAIDS, 2008), in 2007 about 67 per cent of all HIV-infected patients in the world were in Sub-Saharan Africa, with 35% of new infections and 38% of the AIDS deaths occurring in Southern Africa. Globally, the number of children younger than 15 years of age infected with HIV increased from 1.6 million in 2001 to 2.0 million in 2007 and almost 90% of these were in Sub-Saharan Africa. (UNAIDS, 2008).^ Both clinical and laboratory monitoring of children on Highly Active Anti-Retroviral Therapy (HAART) are important and necessary to optimize outcomes. Laboratory monitoring of HIV viral load and genotype resistance testing, which are important in patient follow-up to optimize treatment success, are both generally expensive and beyond the healthcare budgets of most developing countries. This is especially true for the impoverished Sub-Saharan African nations. It is therefore important to identify those factors that are associated with virologic failure in HIV-infected Sub-Saharan African children. This will inform practitioners in these countries so that they can predict which patients are more likely to develop virologic failure and therefore target the limited laboratory monitoring budgets towards these at-risk patients. The objective of this study was to examine those factors that are associated with virologic failure in HIV-infected children taking Highly Active Anti-retroviral Therapy in Botswana, a developing Sub-Saharan African country. We examined these factors in a Case-Control study using medical records of HIV-infected children and adolescents on HAART at the Botswana-Baylor Children's Clinical Center of Excellence (BBCCCOE) in Gaborone, Botswana. Univariate and Multivariate Regression Analyses were performed to identify predictors of virologic failure in these children.^ The study population comprised of 197 cases (those with virologic failure) and 544 controls (those with virologic success) with ages ranging from 3 months to 16 years at baseline. Poor adherence (pill count <95% on at least 3 consecutive occasions) was the strongest independent predictor of virologic failure (adjusted OR = 269.97, 95% CI = 104.13 to 699.92; P < 0.001). Other independent predictors of virologic failure identified were: First Line NNRTI with Nevirapine (OR = 2.99, 95% CI = 1.19 to7.54; P = 0.020), Baseline HIV-1 Viral Load >750,000/ml (OR = 257, 95% CI = 1.47 to 8.63; P = 0.005), Positive History of PMTCT (OR = 11.65, 95% CI = 3.04-44.57; P < 0.001), Multiple Care-givers (>=3) (OR = 2.56, 95% CI = 1.06 to 6.19; P = 0.036) and Residence in a Village (OR = 2.85, 95% CI = 1.36 to 5.97; P = 0.005).^ The results of this study may help to improve virologic outcomes and reduce the costs of caring for HIV-infected children in resource-limited settings. ^ Keywords: Virologic Failure, Highly Active Anti-Retroviral Therapy, Sub-Saharan Africa, Children, Adherence.^

Understanding causes of hospitalization and access to care among newly diagnosed HIV patients in Houston, TX

More than a quarter of patients with HIV in the United States are diagnosed in hospital settings most often with advanced HIV related conditions.(1) There has been little research done on the causes of hospitalization when the patients are first diagnosed with HIV. The aim of this study was to determine if the patients are hospitalized due to an HIV related cause or due to some other co-morbidity. Reduced access to care could be one possible reason why patients are diagnosed late in the course of the disease. This study compared the access to care of patients diagnosed with HIV in hospital and outpatient setting. The data used for the study was a part of the ongoing study “Attitudes and Beliefs and Steps of HIV Care”. The participants in the study were newly diagnosed with HIV and recruited from both inpatient and outpatient settings. The primary and the secondary diagnoses from hospital discharge reports were extracted and a primary reason for hospitalization was ascertained. These were classified as HIV-related, other infectious causes, non–infectious causes, other systemic causes, and miscellaneous causes. Access to care was determined by a score based on responses to a set of questions derived from the HIV Cost and Services Utilization Study (HCSUS) on a 6 point scale. The mean score of the hospitalized patients and mean score of the patients diagnosed in an outpatient setting was compared. We used multiple linear regressions to compare mean differences in the two groups after adjusting for age, sex, race, household income educational level and health insurance at the time of diagnosis. There were 185 participants in the study, including 78 who were diagnosed in hospital settings and 107 who were diagnosed in outpatient settings. We found that HIV-related conditions were the leading cause of hospitalization, accounting for 60% of admissions, followed by non-infectious causes (20%) and then other infectious causes (17%). The inpatient diagnosed group did not have greater perceived access-to-care as compared to the outpatient group. Regression analysis demonstrated a statistically significant improvement in access-to-care with advancing education level (p=0.04) and with better health insurance (p=0.004). HIV-related causes account for many hospitalizations when patients are first diagnosed with HIV. Many of these HIV-related hospitalizations could have been prevented if patients were diagnosed early and linked to medical care. Programs to increase HIV awareness need to be an integral part of activities aimed at control of spread of HIV in the community. Routine testing for HIV infection to promote early HIV diagnosis can prevent significant morbidity and mortality.^

Sub-epidemics explain localized high prevalence of reduced susceptibility to Rilpivirine in treatment-naive HIV-1-infected patients: subtype and geographic compartmentalization of baseline resistance mutations

This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Competencies Required in Education Research and Teaching Systematization according to Students from the Preschool, Primary and Secondary Education Programs of the University of Costa Rica

The purpose of this paper is to present the results of two online forums carried out with the participation of 42 students of the Licenciaturas  in Preschool Education, Primary Education and Secondary Education of the University of Costa Rica. The main purpose of the forums was to determine the insights of the participant students about the competencies they have achieved in the field of education research, and which have been the essential tools for them to systematize their own teaching practices. The discussion forums were part of the course FD5091 Métodos de Investigación Educativa [Education Research Methods] of the School of Teacher Education, delivered from March-April 2010.  Of the sample, 60 percent were students of the Preschool teaching program, 35 percent were from the Primary Education teaching program and 5 percent were from the Secondary Education teaching program in the fields of Science, Mathematics and Social Studies. According to the insights and beliefs showed by the participants –both, the future teachers and the profession practitioners–, there are no opportunities for research or systematization of their own teaching mediation, in the current work situation.(1) Translator’s Note: In Costa Rica, the “Licenciatura” is a one-year post-Bachelor study program, usually including thesis. “Primary Education” refers to students from the 1st to 6th grades, and “Secondary Education” refers to students from the 7th to 11th grades.

HealthMap: A cluster randomised trial of interactive health plans and self-management support to prevent coronary heart disease in people with HIV

Background The leading causes of morbidity and mortality for people in high-income countries living with HIV are now non-AIDS malignancies, cardiovascular disease and other non-communicable diseases associated with ageing. This protocol describes the trial of HealthMap, a model of care for people with HIV (PWHIV) that includes use of an interactive shared health record and self-management support. The aims of the HealthMap trial are to evaluate engagement of PWHIV and healthcare providers with the model, and its effectiveness for reducing coronary heart disease risk, enhancing self-management, and improving mental health and quality of life of PWHIV. Methods/Design The study is a two-arm cluster randomised trial involving HIV clinical sites in several states in Australia. Doctors will be randomised to the HealthMap model (immediate arm) or to proceed with usual care (deferred arm). People with HIV whose doctors are randomised to the immediate arm receive 1) new opportunities to discuss their health status and goals with their HIV doctor using a HealthMap shared health record; 2) access to their own health record from home; 3) access to health coaching delivered by telephone and online; and 4) access to a peer moderated online group chat programme. Data will be collected from participating PWHIV (n = 710) at baseline, 6 months, and 12 months and from participating doctors (n = 60) at baseline and 12 months. The control arm will be offered the HealthMap intervention at the end of the trial. The primary study outcomes, measured at 12 months, are 1) 10-year risk of non-fatal acute myocardial infarction or coronary heart disease death as estimated by a Framingham Heart Study risk equation; and 2) Positive and Active Engagement in Life Scale from the Health Education Impact Questionnaire (heiQ). Discussion The study will determine the viability and utility of a novel technology-supported model of care for maintaining the health and wellbeing of people with HIV. If shown to be effective, the HealthMap model may provide a generalisable, scalable and sustainable system for supporting the care needs of people with HIV, addressing issues of equity of access. Trial registration Universal Trial Number (UTN) U111111506489; ClinicalTrial.gov Id NCT02178930 submitted 29 June 2014