bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of transmitted drug resistance and HIV‐1 subtypes using dried serum spots of recently HIV‐infected individuals in 2013 in Germany
Authors: Andrea Hauser , Alexandra Hofmann , Claudia Santos‐Hoevener , Ruth Zimmermann , Osamah Hamouda , Norbert Bannert , Claudia Kuecherer
Published: November 2014

Introduction

The Robert Koch Institute (RKI) aimed to assess a molecular surveillance strategy based on filter‐dried serum spots (DSS) of all newly diagnosed HIV infections in Germany. In 2013, diagnostic laboratories sent DSS to the RKI representing 55% of the newly diagnosed HIV infections reported to the RKI (protection against infection act). DSS were first tested serologically to identify recently acquired infections (<140 days duration of infection); those classified as “recent infection” were processed for HIV‐1 genotyping. The aim of this study was to assess the level of TDR and the current HIV‐1 subtypes in the main HIV transmission group categories (TrGrpC) in 2013: men who have sex with men (MSM), women/men with heterosexual contacts (HET) and injecting drug users (IDUs).

Materials and Methods

DSS were tested for recency of infection using the BED capture EIA. Viral RNA from “recent infections” was amplified by HIV‐1 group M generic pol‐RT‐PCR covering all resistance‐associated positions in the HIV‐1 protease (AS1‐99) and reverse transcriptase (AS1‐252) if viral loads were ≥6,500 copies/mL. PCR amplicons were sequenced (Sanger) to analyze genotypic resistance and the HIV‐1 subtype. Results were merged to data from the HIV report, i.e. the TrGrpC.

Results

In 2013, 1027 DSS were classified as recent HIV infections (506 MSM, 118 HET, 31 IDUs, 6 others, 366 unknown). RNA was extracted from 703 recent cases and 389/503 samples with sufficient viral load were PCR‐positive. By June 2014, 276/389 samples were sequenced: TDR was identified in 13% (35/276) of the recent infections including single (PI, NRTI, NNRTI) and dual drug class resistant strains (NRTI/NNRTI; NNRTI/PI). 18% (51/276) of recent HIV‐1 infections were caused by non‐B subtypes (A1, C, CRF01_AE, CRF02_AG, D, F, G, URFs). TDR was observed at comparable levels in all TrGrpC. Proportions of non‐B infections were significantly higher in HET (78%; 14/18) and IDUs (60%; 3/5) compared to MSM (8%; 14/169) (p<0.01).

Conclusions

The proportion of TDR was similar but the proportion of HIV‐1 subtype non‐B infections was higher as previously described for Germany based on results from the German HIV‐1 Seroconverter Cohort [1,2]. This difference could be the result of a broadened inclusion of HET and IDUs due to the sampling method used making this study representative for molecular surveillance of HIV‐1 in Germany.
Everything fine so far? Physical and mental health in HIV‐infected patients with virological success and long‐term exposure to antiretroviral therapy
Authors: Erdbeer Gesa , Sabranski Michael , Sonntag Ina , Stoehr Albrecht , Horst Heinz‐A. , Plettenberg Andreas , Schewe Knud , Unger Stefan , Stellbrink Hans‐J. , Fenske Stefan , Hoffmann Christian
Published: November 2014

Introduction

Little is known about the well‐being on long‐term exposure to antiretroviral therapy. The ACTG Augmented Symptoms Distress Module (ASDM) is a validated tool which measures the presence of a total of 22 symptoms seen with HIV and quantifies the extent to which they cause distress to the patient.

Methods

ELBE was a cross‐sectional study that consecutively included adult HIV‐infected patients presenting with viral suppression (<50 HIV RNA copies/mL) and ART exposure for at least five years. Patients were evaluated by four different questionnaires, including ASDM.

Results

Of a total of 894 patients included in the three participating ELBE centres, complete data on ASDM were available for 698 patients (626 male, 69 female, 3 transsexual). Median age was 49.7 years (range, 23.3–82.5 years) and median exposure to ART was 11.5 years (range, 5–28 years). Median CD4 T‐cell counts had increased from a CD4 nadir of 180 to currently 640 cells/µL. Despite immunological and virological success, a high degree of symptom‐related distress was noted in this patient population. In total, 63.8% and 36.3% of the patients had at least one “bothersome” or one “very bothersome” symptom, respectively. The symptoms most frequently reported to be “bothersome” or “very bothersome” were fatigue and energy loss (18.5% and 11.0% respectively), insomnia (12.8% and 11.6%), sadness and depression (13.0% and 10.0%), sexual dysfunction (12.0% and 10.0%), and changes in body appearance (11.0% and 10.9%). There was no association between the degree of symptom‐related distress and gender, age or CD4 T‐cell nadir. However, the history of AIDS‐defining illnesses, comorbidities such as depression but also the duration of ART were significantly associated with a higher overall symptom summary score and with a higher frequency of symptoms. For example, in patients with at least 15 years of ART exposure, only 27.3% of the patients did not report at least one “bothersome” or “very bothersome” symptom.

Conclusions

In this large group of positively selected HIV+ patients with virological success and long‐term exposure to ART, a high degree of symptom‐related distress was found. Medical care of HIV‐infected patients should not only focus on optimal virological outcome. More data on quality of life in patients with long‐term exposure to ART is needed.
Detection of resistance mutations and CD4 slopes in individuals experiencing sustained virological failure
Authors: Schultze Anna , Paredes Roger , Sabin Caroline , Phillips Andrew N , Pillay Deenan , Kirk Ole , Lundgren Jens D , Pozniak Anton , Nelson Mark , Cozzi‐Lepri Alessandro ,   on behalf of Eurosida in Eurocoord
Published: November 2014

Introduction

Several resistance mutations have been shown to affect viral fitness, and the presence of certain mutations might result in clinical benefit for patients kept on a virologically failing regimen due to an exhaustion of drug options. We sought to quantify the effect of resistance mutations on CD4 slopes in patients undergoing episodes of viral failure.

Materials and Methods

Patients from the EuroSIDA and UK CHIC cohorts undergoing at least one episode of virological failure (>3 consecutive RNA measurements >500 on ART) with at least three CD4 measurements and a resistance test during the episode were included. Mutations were identified using the IAS‐US (2013) list, and were presumed to be present from detection until the end of an episode. Multivariable linear mixed models with a random intercept and slope adjusted for age, baseline CD4 count, hepatitis C, drug type, RNA (log‐scale), risk group and subtype were used to estimate CD4 slopes. Individual mutations with a population prevalence of >10% were tested for their effect on the CD4 slope.

Results

A total of 2731 patients experiencing a median of 1 (range 1–4) episodes were included in this analysis. The prevalence of any resistance per episode was 88.4%; NNRTI resistance was most common (78.5%). Overall, CD4 counts declined by 17.1 (−19.7; −14.5) cells per year; this decline was less marked with partial viral suppression (current HIV RNA more than 1.5 log below the setpoint; p=0.01). In multivariable models adjusting for viral load, CD4 decline was slower during episodes with detected resistance compared to episodes without detected resistance (21.0 cells/year less, 95% CI 11.75–30.31, p<0.001). Among those with more than one resistance mutation, there was only weak evidence that class‐specific mutations had any effect on the CD4 slope (Table 1). The effects of individual mutations (incl. M184V) were explored, but none were significantly associated with the CD4 slope; for these comparisons, a Bonferroni‐corrected p‐value level was 0.003.

Conclusions

In our study population, detected resistance was associated with slightly less steep CD4 declines. This may be due to a biological effect of resistance on CD4 slopes, or other unmeasured factors such as poor adherence among individuals without resistance. Among individuals with detected drug resistance, we found no evidence suggesting that the presence of individual mutations was associated with beneficial CD4 slope changes.
Appearance of NS3 Q80K mutation in HCV genotype 1a mono‐ or HIV/HCV co‐infected patients in a Berlin laboratory
Authors: Ehret Robert , Neifer Stefan , Walter Hauke , Baumgarten Axel , Obermeier Martin
Published: November 2014

Introduction

Simeprevir, a new oral NS3/4A protease inhibitor, was recently approved by the FDA and the EMA for the treatment of patients with chronic HCV genotype 1, 4, 5 and 6 infection l. It has been recommended in the 2014 UK Consensus Guidelines as a possible treatment of previously untreated genotype 1a‐infected patients. The antiviral efficacy of simeprevir is adversely affected by the mutation at the Q80K loci. There is controversial discussion that the incidence of Q80K in the European HCV 1a‐infected community is very low and therefore testing of Q80K before starting a therapy including simeprevir is not necessary. We analyzed the appearance of Q80K in all sequenced HCV NS3A samples in 2014 in our laboratory.

Materials and Methods

All in 2014 received orders for HCV resistance tests were analyzed with an in‐house bulk sequencing method analyzing NS3A amino acids 1–181. Analysis was performed using geno2pheno HCV. The genotype 1a samples were selected, Q80K status and data of HIV co‐infection were collected.

Results

Forty‐two HCV 1a samples were sent to us for resistance analyses from nine different medical centres in Berlin and Hannover, Germany. Nineteen (or 45%) of the sequences showed a Q80K mutation. Six extra clade I viruses had no Q80K mutation. Comparison between mono‐ and HIV‐1 co‐infected patients showed no difference in frequency of Q80K (mono‐infected: 8 out of 19 patients; co‐infected: 9 out of 23). For two 80K‐positive patients, the HIV‐status was not available.

Conclusions

The incidence for Q80K mutation in HCV genotype 1a with overall 45% is substantially high in our cohort and does not differ between mono‐ and HIV‐1 co‐infected patients. Response to simeprevir is affected by the presence of viral Q80K. When treating HCV‐infected patients with a simeprevir containing regimen, it is therefore important that HCV does not contain the Q80K mutation.
New dolutegravir resistance pattern identified in a patient failing antiretroviral therapy
Authors: Carganico Andreas , Dupke Stefan , Ehret Robert , Berg Thomas , Baumgarten Axel , Obermeier Martin , Walter Hauke
Published: November 2014

Introduction

The most recently approved antiretroviral, the integrase inhibitor dolutegravir (DTG), is described to be a very potent drug with a unique resistance profile, but a certain degree of cross‐resistance to RAL or EVG induced drug resistance, which is mediated mainly by integrase mutations at positions 140 and 148. The impact of a single N155H mutation to DTG resistance is described to be minor. However, there is only rare data available about the impact of N155H in the context of secondary site integrase mutations. Here, we present a case of virological failure in a DTG treated patient based on N155H mutation background.

Methods

Therapy monitoring of an HIV‐HCV co‐infected patient harbouring already an omni‐drug‐class resistant HIV‐1 in consequence of more than 20 years ART history. Drug susceptibility testing was performed by RT‐PCR from plasma and subsequent Sanger sequencing. Tropism testing was done from proviral DNA with FPR cut‐offs according to the German recommendations.

Results

In 2013, the patient harbouring a virus with high level resistance to all RTI and PI received a regimen containing FTC, TDF, DRV/r, RPV, T20, and RAL to handle a viral load of 5000 RNA copies/mL, but never achieved fully suppressed viral load. In June 2013, after S119R, N155H and E157Q mutations in viral integrase were detected, the patient received DTG, and RAL was stopped. One month later, when viral load was undetectable for the first time since 2007, ART was de‐escalated by removing T20. Since February 2014, low‐level viral load was re‐detectable. Two new mutations T97A and S147G in the integrase and no other new resistance associated mutations in protease and reverse transcriptase in comparison to the sample analyzed in June 2013 were detected.

Conclusions

Highly resistant HIV‐1 strains have been a common problem in the past. Their frequencies were pushed back by highly potent ART, but the virus is still able to become resistant against all available antiretrovirals at once. The here documented strain became resistant to DTG without carrying mutations at the described positions 140 and 148, but in the context of integrase N155H. Since N155H alone is described not to contribute sufficient resistance to DTG, there seems to be a need to re‐check viruses with N155H plus minor mutations (like T97A, S119R, S147G and E157Q) potentially contributing to DTG resistance.
Determinants of use of the fixed dose combination emtricitabine/rilpivirine/tenofovir (Eviplera) in HIV‐infected persons receiving care in Italy
Authors: Cozzi‐Lepri Alessandro , Lo Caputo Sergio , Maggiolo Franco , Antinori Andrea , Ammassari Adriana , Marchetti Giulia , Mastroianni Claudio , Gori Andrea , Di Perri Giovanni , Angarano Gioacchino , Carbone Alessia , d'Arminio Monforte Antonella ,   Study, on behalf of the ICONA Foundation
Published: November 2014

Introduction

Emtricitabine/rilpivirine/tenofovir (EVP) is a fixed‐dose combination of antiretrovirals (ARV) approved by the European Medicines Agency in November 2011 and introduced in Italy in February 2013. It is a once‐a‐day single tablet and is licensed in Europe for use only in ARV‐naïve patients with a viral load (VL) ≤100,000 copies/mL.

Objective

To identify factors that may be associated with the use of EVP as first‐line regimen in HIV‐infected individuals starting cART from ARV‐naïve in Italy.

Methods

Clinical sites in ICONA Foundation Study in which ≥1 person had started EVP were selected for this analysis. From these we included all patients who started an EVP‐based cART regimen as well as those starting other cART regimens after the date of introduction of EVP at the site (after February 2013 in any case) and with a VL ≤100,000 copies/mL from ARV‐naïve. Characteristics at the time of starting cART were compared using chi‐square test and unadjusted and adjusted logistic regression analysis. Factors investigated included: gender, mode of HIV transmission, time from HIV diagnosis, CD4 count, nation of birth, AIDS, HCV‐status, age, CD8 count, VL, diabetes, smoking, total and HDL cholesterol, eGFR, blood glucose, level of education and employment and site location. Factors showing unadjusted associations with a p‐value of 10% or smaller, were retained in the multivariable model.

Results

We identified 183 patients starting EVP and 173 starting the control regimen from 23 sites. The number of patients starting EVP included at each site ranged from 1 to 12 and the number of those starting the control regimen was similar. The most frequently used drugs in the concurrent group were: TDF (75%), FTC (74%), DRV (39%), ATV/r (26%), LPV/r (9%), EFV (13%) and RAL (14%). In univariable analysis, there were differences in median CD4 count (390 cells/mm3 in EVP versus 348 in controls, p=0.002), time from HIV diagnosis to starting cART (11 versus 3 months, p=0.001) and prevalence of students (6% versus 3%, p=0.07). No differences were observed for all other factors examined. The table shows estimates of the odds ratios (OR) for factors included in the multivariable model.

Conclusions

CD4 count was higher in EVP‐treated patients compared to controls. Guidelines suggest avoiding initiation of EVP in presence of high VL, possibly explaining this residual difference in CD4. There was also a tendency to prescribe EVP to people with perceived lower adherence or hesitant to start or perhaps with a slow progressing disease.
Efficacy of PI monotherapy versus triple therapy for 1964 patients in 10 randomised trials
Authors: Arribas Jose , Girard Pierre‐Marie , Paton Nicholas , Winston Alan , Marcelin Anne‐Genevieve , Elbirt Daniel , Hill Andrew , Blanca Hadacek Maria
Published: November 2014

Introduction

The efficacy of protease inhibitor monotherapy has been analyzed with different endpoints: initial HIV‐1 RNA rebound, long‐term HIV‐1 RNA suppression after re‐intensification, treatment‐emergent drug resistance, neurocognitive testing and HIV‐1 RNA in the cerebrospinal fluid (CSF).

Methods

A PUBMED search identified nine randomised trials of PI monotherapy versus triple therapy in patients with HIV RNA<50 copies/mL at baseline. Results from the recently completed PROTEA trial were also included. The percentage of patients with HIV RNA suppression <50 copies/mL was analyzed using switch equals failure and intensification included endpoints (ITT). The number of patients with new drug resistance mutations, HIV RNA in the CSF or change in neurocognitive function was analyzed by treatment arm.

Results

Four trials evaluated darunavir/r monotherapy (n=785: MONET, MONOI, MONARCH, PROTEA), five evaluated lopinavir/r monotherapy (n=592: OK‐04, KalMo, KALESOLO, KRETA, MOST) and one evaluated both (MRC PIVOT, n=587). HIV‐1 RNA suppression rates tended to be lower on PI monotherapy than triple therapy in “switch equals failure” analysis (76% vs 82%), but not when the outcome of intensification was included (87% vs 85%). There were small numbers of patients taking PI monotherapy with detectable HIV‐1 RNA in the CSF, in three trials: PROTEA (n=2), MONOI (n=2) and MOST (n=5), but only two cases of CSF viral escape (MONOI). In two trials, there was no difference in neurocognitive test results between PI monotherapy and triple therapy, based on z‐scores from five domains (in PROTEA, mean change in NPZ‐5 score=0.0 for DRV/r monotherapy vs −0.10 for triple therapy); similar results were observed in the MRC PIVOT trial. The risk of treatment emergent NRTI or PI resistance (Table 1) was 11/973 (1.1%) for patients on PI monotherapy, versus 7/991 (0.7%) for patients on triple therapy.

Conclusions

In 10 randomised trials of 1964 patients with HIV‐1 RNA suppression at baseline, PI monotherapy showed a higher risk of HIV RNA elevations, and small numbers with HIV RNA detectable in CSF and concomitantly in the plasma. However there was no increased risk of treatment‐emergent drug resistance, neurocognitive endpoints were not different between the arms and HIV‐1 RNA suppression rates after intensification were similar between PI monotherapy and triple therapy.
Durability of lopinavir/ritonavir dual‐therapies in individuals with viral load <50 copies/mL in the observational setting
Authors: Gianotti Nicola , Cozzi‐Lepri Alessandro , Antinori Andrea , Di Biagio Antonio , Cristina Moioli Maria , Nozza Silvia , Cingolani Antonella , De Luca Andrea , Madeddu Giordano , Bonora Stefano , Ceccherini‐Silberstein Francesca , d'Arminio Monforte Antonella ,   Study on behalf of ICONA Foundation
Published: November 2014

Introduction

We aimed at evaluating the efficacy and durability of a lopinavir/ritonavir‐based dual regimen (LPV/r‐DR) in virologically controlled HIV‐infected individuals in current clinical practice.

Methods

Patients who have initiated for the first time a LPV/r‐DR with HIV‐RNA<50 copies/mL were included in this observational study. The main endpoints were: time to virological rebound [VR=time of first of two consecutive viral loads (VL)>50 copies/mL] and time to experience either a single VL>200 copies/mL or discontinuation/intensification (= treatment failure, TF). Individuals’ follow‐up accrued from the date of starting the LPV/r‐DR to event or last available VL. Kaplan‐Meier curves and Cox regression analysis were used. Covariates included in the multivariable analysis were gender, age, route of transmission, hepatitis co‐infection, calendar year of starting the DR, nadir CD4+ count, VL at initiation of first cART, previous failures to protease inhibitors (PIs), time with undetectable VL before starting the DR and the type of DR [nucleoside reverse transcriptase (NRTI), non‐NRTI (NNRTI), raltegravir or maraviroc, with NRTI as reference group]. Results are presented as median (Q1, Q3) or frequency (%) as appropriate.

Results

108 individuals followed for 18 (7, 30) months were included; baseline (BL) characteristics are detailed in Table 1.

LPV/r was associated with a NRTI in 51, with a NNRTI in 10, with raltegravir in 29, and with maraviroc in 18 individuals. By 36 months from switching to the LPV/r‐DR, the proportion of individuals with VR and TF was 10% (95% CI 3–17%) and 36% (95% CI 22–50%), respectively. We did not find any factor independently associated with the risk of VR. Older age (ARH=0.49 (95% CI 0.30–0.78) per 10 years older; p=0.003) was found to be protective from TF. Mean (SE) CD4+ cells/µL increase from BL to month 36 resulted significant: 195 (40.1) cells/µL (p=0.0028). We did not observe significant changes in AST, ALT, eGFR (MDRD formula), triglycerides and both total and HDL‐cholesterol.

Conclusions

A LPV/r‐DR can be considered a valuable option in patients with HIV‐RNA<50 copies/mL and ongoing toxicity from the third drug of the regimen, although up to 17% of patients showed viral rebound by 3 years. Older patients are at lower risk of failure with this strategy, but larger sample size is needed to identify who might benefit from this strategy instead of others.
Lamivudine plus darunavir boosted with ritonavir as simplification dual regimen in HIV‐infected patients
Authors: Luis Casado Jose , Bañón Sara , Moreno Ana , Diaz de Santiago Alberto , Gomez Cristina , Perez‐Elías María J , Moreno Santiago
Published: November 2014

Introduction

The combination of lamivudine plus a protease inhibitor boosted with ritonavir (PI/r) has become an alternative as simplification strategy in HIV‐infected patients with toxicity/intolerance to other nucleoside analogues (NA). Lamivudine plus darunavir/r (DRV/r) could be an adequate once daily option.

Materials and Methods

Prospective cohort study of 48 HIV‐infected patients on suppressive triple therapy‐based HAART, HBV negative, who switched to lamivudine 300 mg plus DRV/r 800/100 mg once daily.

Results

Mean age was 50 yrs (35–74), and 65% were male. Thirty patients (63%) had HCV co‐infection (fibrosis 4 in 7 cases, 23%). Median time of HIV infection was 19.1 years, and CD4+ count nadir was 220 cells/µL (2–604). They had received a mean of three regimens before (2–20), and 20 (42%) had a previous AIDS diagnosis. In eight cases, a previous resistance test showed two to seven secondary mutations in the protease gene, without resistance to DRV/r (one patient with the I84V mutation). At baseline, patients had viral suppression (<50 copies/mL) for a median time of 1263 days (341–1884), and they were receiving predominantly a PI based regimen (ATV in four, FPV in four, LPV in three, DRV in six) or an efavirenz‐based regimen (seven). The main reason to switching to this dual therapy was toxicity (35 patients, 75%), mainly renal toxicity attributed to tenofovir (24 cases). During 104.3 patients‐year of follow‐up (median 912 days), only two patients (4%) failed at 27 and 505 days, due to non‐adherence and lost to follow up, respectively. Total cholesterol and triglycerides increased significantly during the first six months after initiation (TC, from 185 to 269 mg/dL; p=0.01, TG from 118 to 185 mg/dL; p=0.03, TC/HDL ratio, from 4.09 to 4.66) and decreased after. Median estimated glomerular filtration rate (eGFR) improved during follow up (from 86 to 96.1 mL/min; p=0.13). In patients with renal toxicity as cause of switch there was a mild, no significant improvement during the first year (from 63.3 to 68.7 mL/min), although an improvement in protein‐uria levels (protein/creatinine ratio, from 171 to 126 mg/g; p=0.04) was observed soon after initiation.

Conclusions

Dual therapy with lamivudine plus darunavir boosted with ritonavir once daily is safe and effective as simplification strategy in HIV‐infected patients.
Prévenir la maltraitance envers les enfants au moyen du marketing social
Authors: Gagné Marie-Hélène , Lachance Véronique , Thomas Flora , Brunson Liesette , Clément Marie-Ève
Published: November 2014

Le marketing social (MS) constitue une stratégie intéressante en matière de prévention universelle. Il s'est avéré efficace pour réduire l'incidence de divers problèmes de santé publique comme le tabagisme ou la consommation d'aliments sucrés, contribuant à la prévention de plusieurs maladies. Le présent article s'adresse aux chercheurs, décideurs et praticiens et praticiennes qui oeuvrent dans le domaine de la prévention de la maltraitance envers les enfants, afin de les outiller pour élaborer des campagnes de MS efficaces dans ce domaine. Il examine le potentiel de cette approche pour réduire l'incidence des comportements parentaux coercitifs, violents, incohérents ou négligents, et rehausser le recours aux pratiques parentales positives. Les composantes d'une approche de marketing social sont présentées, ainsi que leur application à la prévention de la maltraitance. Les campagnes ayant été évaluées sont recensées et leur efficacité est présentée. L'article met en lumière le caractère prometteur du MS pour prévenir la maltraitance, surtout lorsqu'il intègre une approche communautaire et qu'il est lié à une offre de services directs aux parents.
Preventing Punitive Violence: Preliminary Data on the Positive Discipline in Everyday Parenting (PDEP) Program
Authors: Durrant Joan E. , Plateau Dominique Pierre , Ateah Christine , Stewart-Tufescu Ashley , Jones Alysha , Ly Gia , Barker Leslie , Holden George W. , Kearley Colleen , MacAulay Janice , Peters Ray DeV. , Tapanya Sombat
Published: November 2014

Most physical violence against children is punitive in intent. The United Nations has called for the elimination of physical punishment of children and for the development of programs teaching nonviolent resolution of parent-child conflict. A focused effort is required to shift entrenched, intergenerationally transmitted, and culturally normalized belief systems about physical punishment. Positive Discipline in Everyday Parenting (PDEP) was developed to meet this need. Its short-term objectives are to: 1) reduce approval of physical punishment; 2) normalize parent-child conflict; and 3) strengthen parenting self-efficacy. PDEP was delivered by trained program facilitators to 321 parents living in 14 cities in Canada. Responses to pre and posttest questionnaires suggest that parents who completed postprogram measures were less likely to both approve of physical punishment and view typical parent-child conflict as misbehaviour on the part of the child, and also to have greater parenting self-efficacy. More than 90% believed more strongly that parents should not use physical punishment, and that PDEP would help them control their anger and build stronger relationships with their children. PDEP is a promising approach to the prevention of punitive violence against children.
Folding and Purification of Insoluble (Inclusion Body) Proteins from Escherichia coli
Authors: Wingfield Paul T. , Palmer Ira , Liang Shu‐Mei
Published: November 2014

Heterologous expression of recombinant proteins in E. coli often results in the formation of insoluble and inactive protein aggregates, commonly referred to as inclusion bodies. To obtain the native (i.e., correctly folded) and hence active form of the protein from such aggregates, four steps are usually followed: (1) the cells are lysed, (2) the cell wall and outer membrane components are removed, (3) the aggregates are solubilized (or extracted) with strong protein denaturants, and (4) the solubilized, denatured proteins are folded with concomitant oxidation of reduced cysteine residues into the correct disulfide bonds to obtain the native protein. This unit features three different approaches to the final step of protein folding and purification. In the first, guanidine·HCl is used as the denaturant, after which the solubilized protein is folded (before purification) in an “oxido‐shuffling” buffer system to increase the rate of protein oxidation. In the second, acetic acid is used to solubilize the protein, which is then partially purified by gel filtration before folding; the protein is then folded and oxidized by simple dialysis against water. Thirdly, folding and purification of a fusion protein using metal‐chelate affinity chromatography are described. © 2014 by John Wiley & Sons, Inc.
Low‐latitude ionospheric effects of energetic electrons during a recurrent magnetic storm
Authors: Suvorova A. V. , Huang C.‐M. , Matsumoto H. , Dmitriev A. V. , Kunitsyn V. E. , Andreeva E. S. , Nesterov I. A. , Tsai L.‐C.
Published: November 2014

We study a magnetosphere‐ionosphere coupling at low latitudes during a moderate (corotating interaction regions/high‐speed solar wind streams‐driven) geomagnetic storm on 22 July 2009. Recently, it has been shown that during major (coronal mass ejection‐driven) storms, quasi‐trapped >30 keV electrons largely enhance below the radiation belt in the forbidden zone and produce an additional ionization in the topside ionosphere. In this work, we examine a case of the recurrent storm when the magnetosphere‐ionosphere coupling through the quasi‐trapped electrons also may take place. Data from NOAA/Polar‐orbiting Operational Environmental Satellite and Japanese Greenhouse gases Observing Satellite were used to identify the forbidden electron enhancement (FEE). We find a positive vertical gradient of the electron fluxes that indicates to the radiation belt as a source of FEE. Using global ionospheric maps, radiotomography reconstructions from beacon data and COSMIC/FORMOSAT‐3 radio occultation measurements, we have observed an unusually large area in the nighttime ionosphere with increased total electron content (TEC) and prominent elevation of the F layer at low latitudes that coincides with FEEs spatially and temporarily. Ionizing particles are considered as an addition source of ionization along with generally accepted mechanisms for storm time TEC increase (a positive ionospheric storm). We discuss relative contributions of the FEE and disturbance dynamo electric field in the TEC increases during the storm recovery phase.
Airglow observations of nighttime medium‐scale traveling ionospheric disturbances from Yonaguni: Statistical characteristics and low‐latitude limit
Authors: Lakshmi Narayanan V. , Shiokawa K. , Otsuka Y. , Saito S.
Published: November 2014

The characteristics of nighttime medium‐scale traveling ionospheric disturbance (MSTID) features observed over Yonaguni (24.5°N, 123.0°E; 19.3°N dip latitude), Japan are studied using all‐sky imaging of OI 630.0 nm airglow emission. The uniqueness of these observations is that the area observed by the imager covers the transition region between low to middle latitudes in the ionosphere. Typical low‐latitude limit of midlatitude‐type nighttime MSTIDs possessing phase front alignments along the northwest to the southeast occurs in this region. These MSTID features are rarely sighted at dip latitudes below 15°. We selected 2 year period for analysis in which 1 year corresponded to the solar minimum conditions and another year to the solar maximum conditions. The MSTIDs were observed to extend to farther lower latitudes during the solar minimum conditions than during the solar maximum periods. Their observed range of wavelengths, phase velocities, phase front alignment, and propagation directions are similar to those observed at typical midlatitude sites. However, on many occasions the phase fronts of the observed MSTIDs did not extend over the whole field of view of the imager indicating that some process inhibits their extension to further lower latitudes. Detailed investigation suggests that the poleward propagating enhancement of airglow intensity, probably associated with the midnight pressure bulge, causes the MSTID features to disappear when they reach lower latitudes later in the night. When the MSTIDs reach lower latitudes well before midnight, they are found to be inhibited by the equatorial ionization anomaly crest region.
Association of Low Birth Weight and Preterm Birth With the Incidence of Knee and Hip Arthroplasty for Osteoarthritis
Authors: Hussain Sultana Monira , Wang Yuanyuan , Wluka Anita E. , Shaw Jonathan E. , Magliano Dianna J. , Graves Stephen , Cicuttini Flavia M.
Published: November 2014

Objective

Low birth weight (LBW) and preterm birth have been associated with adverse adult outcomes, including hypertension, insulin resistance, cardiovascular disease, and reduced bone mass. It is unknown whether LBW and preterm birth affect the risk of osteoarthritis (OA). This study aims to examine whether LBW and preterm birth were associated with the incidence of knee and hip arthroplasty for OA.

Methods

A total of 3,604 participants of the Australian Diabetes, Obesity and Lifestyle Study who reported their birth weight and history of preterm birth and were age >40 years at the commencement of arthroplasty data collection comprised the study sample. The incidence of knee and hip replacement for OA during 2002–2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry.

Results

One hundred and sixteen participants underwent knee arthroplasty and 75 underwent hip arthroplasty for OA. LBW (yes versus no; hazard ratio [HR] 2.04, 95% confidence interval [95% CI] 1.11–3.75, P = 0.02) and preterm birth (yes versus no; HR 2.50, 95% CI 1.29–4.87, P = 0.007) were associated with increased incidence of hip arthroplasty independent of age, sex, body mass index, education level, hypertension, diabetes mellitus, smoking, and physical activity. No significant association was observed for knee arthroplasty.

Conclusion

Although these findings will need to be confirmed, they suggest that individuals born with LBW or at preterm are at increased risk of hip arthroplasty for OA in adult life. The underlying mechanisms warrant further investigation.
Grips and hand movements of chimpanzees during feeding inMahaleMountainsNationalPark,Tanzania
Authors: Marzke Mary W. , Marchant Linda F. , McGrew William C. , Reece Sandra P.
Published: November 2014

It has long been assumed that stone tool making was a major factor in the evolution of derived hominin hand morphology. However, stresses on the hand associated with food retrieval and processing also have been recognized as relevant early hominin behaviors that should be investigated. To this end, chimpanzee food manipulation was videotaped in the Mahale Mountains National Park, Tanzania. Grips and hand movements by 39 chimpanzees were analyzed for arboreal and terrestrial feeding involving 10 food‐types and associated vegetation. It was predicted that (1) new grips would be found that had not been observed in captivity, (2) forceful precision grips would be absent from the repertoire, as in captivity, and (3) precision handling would be observed. New grips involving the full thumb and buttressed index finger, and a new integrated pattern of grips and forceful hand movements were discovered, associated with feeding on large fruits and meat. Participation of the full thumb in these grips, rather than the distal thumb and fingers, throws light on feeding behaviors that may have become increasingly significant factors in the evolution of derived hominin thumb morphology. The proximal thumb stabilizes food with the flexed index finger against the pull of the teeth and provides leverage in breaking food into portions. Isolated qualitative observations of possibly forceful pinch by the thumb and side of the index finger highlight the need for comparative quantitative data to test whether humans are unique in forceful precision gripping capability. Precision handling was not seen. Am J Phys Anthropol 156:317–326, 2015. © 2014 Wiley Periodicals, Inc.
Coagulase‐negative Staphylococcus culture in chronic rhinosinusitis
Authors: Zhang Zi , Adappa Nithin D. , Lautenbach Ebbing , Chiu Alexander G. , Doghramji Laurel J. , Cohen Noam A. , Palmer James N.
Published: November 2014

Background

Coagulase‐negative Staphylococcus (CoNS) is commonly isolated from patients with chronic rhinosinusitis (CRS). However, the role of CoNS in CRS remains controversial. We aimed to determine the association between positive CoNS culture at functional endoscopic sinus surgery (FESS) and CRS severity.

Methods

Adult CRS patients who underwent FESS between October 1, 2007 to December 31, 2011 were recruited. Patient demographics, disease characteristics, medication use, Lund‐Mackay computed tomography (CT) scores, and 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores were collected at baseline before FESS. Intraoperative cultures were obtained in a standard manner. Patients were placed into 2 groups based on culture findings: patients with CoNS as the sole positive culture result and patients with all other positive culture results, including CoNS, as part of a polymicrobial culture.

Results

A total of 376 CRS patients met the criteria; 106 patients (28%) had CoNS as their only isolate, 260 (69%) had other positive cultures, and 10 (3%) had no bacterial growth. Compared to patients with other positive cultures, patients with the sole result of CoNS were significantly less likely to have a history of FESS (52% vs 65%, p = 0.019), nasal polyps (50% vs 65%, p = 0.006), and had a better Lund‐Mackay CT score (11.95 vs 14.18, p = 0.020). After adjusting for all factors in the multiple logistic regression model, CoNS as the sole positive culture result was independently associated with having no history of FESS (odds ratio [OR] = 0.45; 95% confidence interval [CI], 0.22 to 0.94; p = 0.034).

Conclusion

Positive intraoperative CoNS cultures alone do not result in increased CRS disease burden by objective or subjective measures as compared to patients with other bacterial or polymicrobial culture isolates.
Fabrication of Polyhedral Particles from Spherical Colloids and Their Self‐Assembly into Rotator Phases
Authors: Vutukuri Hanumantha Rao , Imhof Arnout , van Blaaderen Alfons
Published: November 2014

Particle shape is a critical parameter that plays an important role in self‐assembly, for example, in designing targeted complex structures with desired properties. Over the last decades, an unprecedented range of monodisperse nanoparticle systems with control over the shape of the particles have become available. In contrast, the choice of micrometer‐sized colloidal building blocks of particles with flat facets, that is, particles with polygonal shapes, is significantly more limited. This can be attributed to the fact that in contrast to nanoparticles, the larger colloids are significantly harder to synthesize as single crystals. It is now shown that a very simple building block, such as a micrometer‐sized polymeric spherical colloidal particle, is already enough to fabricate particles with regularly placed flat facets, including completely polygonal shapes with sharp edges. As an illustration that the yields are high enough for further self‐assembly studies, the formation of three‐dimensional rotator phases of fluorescently labelled, micrometer‐sized, and charged rhombic dodecahedron particles was demonstrated. This method for fabricating polyhedral particles opens a new avenue for designing new materials.
Enzymatic Methylation and Structure–Activity‐Relationship Studies on Polycarcin V, a Gilvocarcin‐Type Antitumor Agent
Authors: Chen Jhong‐Min , Shepherd Micah D. , Horn Jamie , Leggas Markos , Rohr Jürgen
Published: November 2014

Polycarcin V, a polyketide natural product of Streptomyces polyformus, was chosen to study structure–activity relationships of the gilvocarcin group of antitumor antibiotics due to a similar chemical structure and comparable bioactivity with gilvocarcin V, the principle compound of this group, and the feasibility of enzymatic modifications of its sugar moiety by auxiliary O‐methyltransferases. Such enzymes were used to modify the interaction of the drug with histone H3, the biological target that interacts with the sugar moiety. Cytotoxicity assays revealed that a free 2′‐OH group of the sugar moiety is essential to maintain the bioactivity of polycarcin V, apparently an important hydrogen bond donor for the interaction with histone H3, and converting 3′‐OH into an OCH3 group improved the bioactivity. Bis‐methylated polycarcin derivatives revealed weaker activity than the parent compound, indicating that at least two hydrogen bond donors in the sugar are necessary for optimal binding.
A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C
Authors: Lehr Konrad , Schulthoff Saskia , Ueda Yoshihiro , Mariz Ronaldo , Leseurre Lucie , Gabor Barbara , Fürstner Alois
Published: November 2014

Lactones are known to react with the reagent generated in situ from CCl4 and PPh3 in a Wittig‐type fashion to give gem‐dichloro‐olefin derivatives. Such compounds are now shown to undergo reductive alkylation on treatment with organolithium reagents RLi to furnish acetylene derivatives bearing the substituent R at their termini (R=Me, n‐, sec‐, tert‐alkyl, silyl); the reaction can be catalyzed with either Cu(acac)2 or Fe(acac)3/1,2‐diaminobenzene. Two alkynol derivatives prepared in this way from readily accessible lactone precursors served as the key building blocks for the total syntheses of the cytotoxic marine macrolides tulearin A (1) and C (2). The assembly of these fragile targets hinged upon ring closing alkyne metathesis (RCAM) followed by a formal trans‐reduction of the resulting cycloalkynes via trans‐hydrosilylation/protodesilylation.
Asymmetric Synthesis of Allylic Sulfonic Acids: Enantio‐ and Regioselective Iridium‐Catalyzed Allylations of Na2SO3
Authors: Liu Wei , Zhao Xiao‐ming , Zhang Hong‐bo , Zhang Liang , Zhao Ming‐zhu
Published: November 2014

An enantioselective allylation reaction of allylic carbonates with sodium sulfite (Na2SO3) catalyzed by Ir complex was accomplished, providing allylic sulfonic acids in good to excellent yields with a high level of enantio‐ and regioselectivities. (R)‐2‐Phenyl‐2‐sulfoacetic acid, a key intermediate for the synthesis of Cefsulodin and Sulbenicillin, was synthesized as well.
Chemistry of Lipid A: At the Heart of Innate Immunity
Authors: Molinaro Antonio , Holst Otto , Di Lorenzo Flaviana , Callaghan Maire , Nurisso Alessandra , D'Errico Gerardino , Zamyatina Alla , Peri Francesco , Berisio Rita , Jerala Roman , Jiménez‐Barbero Jesús , Silipo Alba , Martín‐Santamaría Sonsoles
Published: November 2014

Invited for the cover of this issue is an international collaboration of groups from Italy, Germany, Ireland, Switzerland, Austria, Spain, and Slovenia. The image depicts the chemical aspects behind (and responsible for) the bioactivity of lipid A. Read the full text of the article at 10.1002/chem.201403923.
Synthesis of Microporous Nitrogen‐Rich Covalent‐Organic Framework and Its Application in CO2 Capture
Authors: Gao Qiang , Bai Linyi , Zhang Xiaojing , Wang Peng , Li Peizhou , Zeng Yongfei , Zou Ruqiang , Zhao Yanli
Published: November 2014

An imine‐based nitrogen‐rich covalent‐organic framework (COF) was successfully synthesized using two triangular building units under solvothermal reaction condition. The gas adsorption properties of the obtained microporous nitrogen‐rich COF were investigated. The results indicated that the activated COF material presented good up take capabilities of CO2 and CH4 at 61.2 and 43.4 cm3·g−1 at 1 atm and 273 K, respectively, showing its application potential in selective gas capture and separation.
Numerical investigation of basin‐scale storage of CO2 in saline aquifers of Songliao Basin, China
Authors: Zhao Ruirui , Cheng Jianmei , Zhang Keni , Liu Ning , Xu Fuqiao
Published: November 2014

This paper presents a basin‐scale model study of the behaviors of CO2 plume and the potential environmental impacts for large‐scale CO2 storage in the saline aquifers of Songliao Basin, China. The model covers the whole basin, and vertically consists of most of the Cretaceous strata. In a hypothetical scenario, a total of 1.43 GT CO2 is injected into the Yaojia Formation (K2y) through 20 wells distributing at the center of the basin in 50 years (0.5–2 million tons per injection well per year). The preliminary results show the permeable Yaojia Formation (K2y) with a thickness of 100–400 m at the center of the basin can store large amounts of CO2. The overlying Nenjiang Formation (K2n) with low permeability and large thickness has the potential to ensure long‐term storage security. The high solubility of CO2 of the formation water in this continental basin is a favorable condition for the storage security. The maximum extent of the CO2 plume from different injection wells ranges from about 4 km to 20 km at 1000 years. The maximum pressure build‐up in the Nenjiang Formation (K2n) and the Yaojia Formation (K2y) reaches 8.6 MPa and 9.3 MPa, respectively. An entry capillary pressure of 1 MPa may be enough for the caprock to seal CO2 in the large‐scale CO2 storage. The mudstone layers in the Nenjiang Formation (K2n) can play a crucial role in restraining upward brine migration.© 2014 Society of Chemical Industry and John Wiley & Sons, Ltd
Sustained groundwater level changes and permeability variation in a fault zone following the 12 May 2008, Mw 7.9 Wenchuan earthquake
Authors: Shi Zheming , Wang Guangcai
Published: November 2014

We analyse the groundwater level changes following the Wenchuan earthquake in three wells – NX, DZ and BBLY – located in the same fault zone, in the near field (distance of ~300 km from the epicentre). Co‐seismic falls in the water level and gradual recovery were recorded in these wells but with different recovery periods (from 200 days to more than 1600 days). The response of the groundwater level to Earth tides is used as a proxy to explore the permeability evolution. We found that the permeability increased in response to the Wenchuan earthquake in the three wells but with different post‐earthquake recovery processes. Only BBLY recovered to its pre‐earthquake value 260 days after the Wenchuan earthquake and remained stable. The permeability in NX returned to its pre‐earthquake value over a similar period but then continued to drop. The permeability in DZ returned to its pre‐earthquake value much quicker than that in the other two wells and remained stable below the pre‐earthquake value 200 days after the earthquake. This suggests that the groundwater level changes in the three wells were mainly caused by permeability changes. In the BBLY well, the unclogging/clogging of the fracture flow path mechanism may explain the permeability evolution, whereas mechanisms such as unclogging/clogging or the opening/closing of the fracture associated with blocking of the narrow fracture apertures appears to be responsible for the permeability evolution in the NX and DZ wells. Copyright © 2014 John Wiley & Sons, Ltd.