bluuebunny/crossref_metadata_2025 huggingface dataset:
Margot Ruben: Freundin und Vertraute (1908-1980)
Authors: Koch Renate
Published: February 2017

Marrgot Ruben, Wolfskehl
Job in Auckland: Karl Wolfskehl's Poetry in the Light of the Jewish Job, the Topos of the Galut. and the Lurianic Theme of God's Exile from Himself
Authors: Simms Norman
Published: February 2017

Wolfskehl
Das permanente Exil. Zu Karl Wolfskehls antimoderner Lyrik
Authors: Berendse Gerrit-Jan
Published: February 2017

Wolfskehl. Lyrik
'Was war, ist Rauch'. Expressions of Exodus in the Poetry of Paul Celan and Karl Wolfskehl
Authors: Wareham Evelyn
Published: February 2017

Wolfskehl, Celan
"Ein Lichtpunkt von demanthaftem Feuer": Karl Wolfskehl's Visit to Dunedin
Authors: Ryan Simon
Published: February 2017

Wolfskehl, Dunedin
"A Stranger Arrives": The Art and Writing of Frederick Ost in New Zealand
Authors: Bell Leonard
Published: February 2017

Fredrick Ost
Erinnerungen
Authors: Blumenfeld Konrad
Published: February 2017

Wolfskehl
Ultima Thule. A Reminiscence
Authors: Graham John
Published: February 2017

Wolfskehl
"Die Prinzessin im Mährchen erlösen": Wanderungen durch die Mark Brandenburg
Authors: -- --
Published: February 2017

Fontane
"Mit 78 ist man ein unsicherer Passagier": Fontanes letztes Jahr an der Schwelle zum 20. Jahrhundert
Authors: -- --
Published: February 2017

Fontane
II. Teil: Die Romane
 Vor dem Sturm: "Der schönste deutsche historische Roman"
Authors: -- --
Published: February 2017

Fontane  Vor dem Sturm
Schach von Wuthenow: Wuthenow oder Venedig. Schachs Reisefantasie im Fontaneschen Kontext
Authors: -- --
Published: February 2017

Fontane Schach von Wuthenow
Cécile: Fürstenmätresse in bürgerlicher Zeit
Authors: -- --
Published: February 2017

Fontane Cécile
Effi Briest: Crampas und sein Lieblingsdichter Heine
Authors: -- --
Published: February 2017

Fontane Effi Briest
Zur Zitierweise
Authors: -- --
Published: February 2017

Grawe
Walther von der Vogelweide als Vortragender. Das Mimische und die Strophenfolge seiner Liebeslieder
Authors: Fisher Rodney W.
Published: February 2017

Walther von der Vogelweide
Karoline Pichlers Denkwürdigkeiten: Ein Selbstbekenntnis?
Authors: Alm-Lequeux Antonie
Published: February 2017

Karoline Pichler, Denkwürdigkeiten
Variations of the Lost Hero: Blood on the Ice in Christoph Ransmayer's Schrecken des Eises und der Finsternis
Authors: Cook Lynne
Published: February 2017

Ransmayer, Schrecken des Eises und der Finsternis
Beiträger
Authors: Obermayer August
Published: February 2017

Beiträger
"Kränkung" und "Verdrängung". The Metaphor of Hysteria in Marlen Haushofer's Die Mansarde, und Ingeborg Bachmann's Der Fall Franza.
Authors: Grant Alyth F.
Published: February 2017

Haushofer, Bachmann
Hochwälders Donnerstag oder: Was ein Roman aus dem Jahre 1933 und ein Theaterstück aus dem Jahre1959 außer dem Titel gemeinsam haben
Authors: Obermayer August
Published: February 2017

Hochwälder
Study of phosphorus doped Si:C films formed by in situ doped Si epitaxy and implantation process for n-type metal-oxide-semiconductor devices
Authors: Mochizuki Shogo , Loesing Rainer , Wang Yun-Yu , Jagannathan Hemanth
Published: February 2017

The effect of cluster carbon implantation and recrystallization on properties of phosphorus doped Si (Si:P) epitaxial films was investigated. Recrystallization techniques based on solid phase epitaxy with rapid thermal annealing (RTA), spike RTA (sRTA), and millisecond laser annealing were employed. It was found that strained carbon doped Si:P (Si:CP) layers with high [C]sub can be achieved by using low temperature sRTA/RTA due to the suppression of carbon–phosphorus coclustering in Si. Additional laser annealing can activate the remaining “nonactive” P atoms in the Si:CP layer recrystallized at low temperatures such as 900 °C sRTA and 800 °C 5 s RTA. This approach of combining a low temperature recrystallization anneal with an additional high temperature laser anneal was found to be useful for creating Si:CP layers with good crystallinity, low resistivity, and less phosphorus diffusion. Finally, a tensile strain was confirmed to be induced into the transistor channel by implementing the recrystallization technique on three dimensional fin-shaped field effect transistor device structures. A high recrystallization temperature of 1025 °C sRTA was found to be required for achieving complete recrystallization and suppressing introduction of defects/stacking faults in a Si:CP source/drain region.
Field Day at the Rec: Working Out with Physics
Authors: Young Chadwick , Young Kaisa , Buxton Gavin , Buzzelli Armand
Published: February 2017

Every year, thousands of college students in the life sciences take introductory physics. Some educators have advocated physics be presented in a way that is relevant to these students. Most are biology majors, but many students are in the allied health field studying to become athletic trainers, occupational therapists, or professionals in some other allied health field. These students take a physics course that often has no math prerequisites, covers all of classical physics in a year, and focuses on the physics of the human body.
Engaging Students in a Large-Enrollment Physics Class Using an Academically Focused Social Media Platform
Authors: Gavrin Andy , Lindell Rebecca
Published: February 2017

There are many reasons for an instructor to consider using social media, particularly in a large introductory course. Improved communications can lessen the sense of isolation some students feel in large classes, and students may be more likely to respond to faculty announce-ments in a form that is familiar and comfortable. Furthermore, many students currently establish social media sites for their classes, without the knowledge or participation of their instructors. Such “shadow” sites can be useful, but they can also become distributors of misinformation, or venues for inappropriate or disruptive discussions. CourseNetworking (CN) is a social media platform designed for the academic environment. It combines many features common among learning management systems (LMS’s) with an interface that looks and feels more like Facebook than a typical academic system. We have recently begun using CN as a means to engage students in an introductory calculus-based mechanics class, with enrollments of 150-200 students per semester. This article presents basic features of CN, and details our initial experiences and observations.
Head movements while recognizing speech arriving from behind
Authors: Shen Yi , Folkerts Monica L. , Richards Virgina M.
Published: February 2017

Listeners' head movements were measured during speech recognition with simultaneous maskers. Both the target and masker were behind the listener, separated by 30°. Frequent head turns during speech recognition were observed for four of the ten listeners. For those four, head turns were more frequent at lower target-to-masker ratios (TMRs) and were oriented toward the target speech source. When the masker was competing speech the ultimate head orientation angle was larger at lower TMRs. These observed head movements are not consistent with a strategy that maximizes either the target level at a single ear or binaural unmasking of speech.
Application of acoustic imaging techniques on snowmobile pass-by noise
Authors: Padois Thomas , Berry Alain
Published: February 2017

Snowmobile manufacturers invest important efforts to reduce the noise emission of their products. The noise sources of snowmobiles are multiple and closely spaced, leading to difficult source separation in practice. In this study, source imaging results for snowmobile pass-by noise are discussed. The experiments involve a 193-microphone Underbrink array, with synchronization of acoustic with video data provided by a high-speed camera. Both conventional beamforming and Clean-SC deconvolution are implemented to provide noise source maps of the snowmobile. The results clearly reveal noise emission from the engine, exhaust, and track depending on the frequency range considered.
Lower Body Strength of Children and Adolescents with and Without Mild Mental Retardation: A Comparison
Authors: Pitetti Kenneth H. , Yarmer Daniel A.
Published: February 2017

The purpose of this study was to compare children and adolescents (ages 8-18 yr) with and without mental retardation (MR) on isometric strength of knee flexion, knee extension, and combined leg and back strength. Sample size of participants with mild MR, but without Down syndrome, was 158 males and 111 females. Sample size of peers without MR was 223 males and 226 females. Analysis was made by gender and age: children (8-10 yr), early adolescents (11-14 yr), and late adolescents (15-18 yr). For all age groups, males and females without MR were significantly stronger than their same-gender peers with MR for all isometric strength measurements. For individuals with MR, the trend toward leveling off or decreasing in leg and back strength is a serious health and social concern.
An Inclusion Instrument Based on Planned Behavior Theory for Prospective Physical Educators
Authors: Kudláèek Martin , Válková Hana , Sherrill Claudine , Myers Bettye , French Ron
Published: February 2017

The purpose was to provide validity evidence for an attitude survey that will predict the intention of Czech prospective teachers to include students with physical disabilities in general physical education (GPE). Based on the theory of planned behavior (Ajzen, 1991, 2000), the Czech Attitude Toward Teaching Individuals with Physical Disabilities in Physical Education (ATIPDPE) contained statements of intention and of behavioral, normative, and control beliefs. Attitude was inferred from behavioral beliefs. Content validity evidence was established by experts in two countries and by pilot studies utilizing 96 university students to elicit accessible beliefs and intentions. Construct validity evidence was derived from data collected from 145 GPE and 47 adapted PE prospective teachers enrolled in three universities in the Czech Republic. Bivariate correlations, hierarchical regression analysis, and ANOVA examination of known group difference provided good validity evidence for the ATIPDPE. Alpha coefficients ranged from .71 to .94.
An Abilities-Based Approach to Service Delivery and Professional Preparation in Adapted Physical Activity
Authors: Emes Claudia , Longmuir Patti , Downs Peter
Published: February 2017

Adapted physical activity professionals have embraced for some time the concept of a nonmedical model; however, traditional approaches in service delivery continue to exist. Abilities-based is not a model for service delivery; it is an approach that offers a new perspective that is based on person-centerdness, openness, and compatibility. The focus is on the person in a learning situation, not the disability, not the activity, and not the environment. Although these factors cannot be ignored, emphasis in an ability-based approach shifts to the person. Attitude within and toward service delivery is the critical point of departure in the abilities-based approach. This article discusses demystifying disability and building positive attitudes as features of this approach. It then discusses the influence of this approach on how we prepare future professionals of adapted physical activity, and it concludes with an example of an abilities-based program.
When silencing mRNA, position matters
Authors: Mushegian Alexandra A.
Published: February 2017

The mechanism of posttranscriptional silencing by an RNA-binding protein depends on the position of the protein-binding sequence in the mRNA.
Tamoxifen as an immunotherapy
Authors: Ferrarelli Leslie K.
Published: February 2017

Antiestrogen drugs may treat some estrogen receptor–negative tumors by limiting the proliferation and activity of suppressive immune cells.
Within-Host Selection of Drug Resistance in a Mouse Model Reveals Dose-Dependent Selection of Atovaquone Resistance Mutations
Authors: Nuralitha Suci , Murdiyarso Lydia S. , Siregar Josephine E. , Syafruddin Din , Roelands Jessica , Verhoef Jan , Hoepelman Andy I. M. , Marzuki Sangkot
Published: February 2017

The evolutionary selection of malaria parasites within an individual host plays a critical role in the emergence of drug resistance. We have compared the selection of atovaquone resistance mutants in mouse models reflecting two different causes of failure of malaria treatment, an inadequate subtherapeutic dose and an incomplete therapeutic dose. The two models are based on cycles of insufficient treatment of
Plasmodium berghei
-infected mice: repeated inadequate treatment associated with a subtherapeutic dose (RIaT) (0.1 mg kg
−1
of body weight) and repeated incomplete treatment with a therapeutic dose (RIcT) (14.4 mg kg
−1
of body weight). The number of treatment cycles for the development of a stable resistance phenotype during RIaT was 2.00 ± 0.00 cycles (
n
= 9), which is not statistically different from that during RIcT (2.57 ± 0.85 cycles; combined
n
= 14;
P
= 0.0591). All mutations underlying atovaquone resistance selected by RIaT (M133I, T142N, and L144S) were found to be in the Qo1 (quinone binding 1) domain of the mitochondrial cytochrome
b
gene, in contrast to those selected by RIcT (Y268N/C, L271V, K272R, and V284F) in the Qo2 domain or its neighboring sixth transmembrane region. Exposure of mixed populations of resistant parasites from RIaT to the higher therapeutic dose of RIcT revealed further insights into the dynamics of within-host selection of resistance to antimalarial drugs. These results suggest that both inadequate subtherapeutic doses and incomplete therapeutic doses in malaria treatment pose similar threats to the emergence of drug resistance. RIcT and RIaT could be developed as useful tools to predict the potential emergence of resistance to newly introduced and less-understood antimalarials.
Preclinical Pharmacokinetics and First-in-Human Pharmacokinetics, Safety, and Tolerability of Velpatasvir, a Pangenotypic Hepatitis C Virus NS5A Inhibitor, in Healthy Subjects
Authors: Mogalian Erik , German Polina , Kearney Brian P. , Yang Cheng Yong , Brainard Diana , Link John , McNally John , Han LingLing , Ling John , Mathias Anita
Published: February 2017

Preclinical characterization of velpatasvir (VEL; GS-5816), an inhibitor of the hepatitis C virus (HCV) NS5A protein, demonstrated that it has favorable
in vitro
and
in vivo
properties, including potent antiviral activity against hepatitis C virus genotype 1 to 6 replicons, good metabolic stability, low systemic clearance, and adequate bioavailability and physicochemical properties, to warrant clinical evaluation. The phase 1 (first-in-human) study evaluated the safety, tolerability, and pharmacokinetics of VEL in healthy human subjects following administration of single and multiple (
n
= 7) once-daily ascending doses and of VEL in the presence and absence of food. Following administration of single and multiple doses, VEL was safe and well tolerated when administered at up to 450 mg and when administered with food. The pharmacokinetic behavior of VEL observed in humans was generally in agreement with that seen during preclinical characterization. Following administration of multiple doses, VEL trough concentrations were significantly greater than the protein-adjusted half-maximal (50%) effective concentration of VEL against HCV genotype 1 to 6 replicons at all evaluated doses greater than 5 mg. The pharmacokinetics of VEL were not significantly affected by administration with food. Collectively, the results of this study support the further clinical investigation of VEL administered once daily as part of a regimen with other pangenotypic direct-acting antivirals for the treatment of HCV infection.
Antimicrobial Resistance of Escherichia coli Urinary Isolates in the Veterans Affairs Health Care System
Authors: Morrill Haley J. , Morton Jacob B. , Caffrey Aisling R. , Jiang Lan , Dosa David , Mermel Leonard A. , LaPlante Kerry L.
Published: February 2017

We reviewed data for almost 300,000 clinical
Escherichia coli
urinary isolates (collected in 2009 through 2013) from 127 inpatient and outpatient facilities, to assess antibiotic resistance among Veterans Affairs health care system patients using Clinical and Laboratory Standards Institute and Centers for Disease Control and Prevention National Healthcare Safety Network definitions or guidance. Rates of resistance to amoxicillin or ampicillin/β-lactamase inhibitors were approximately 40% and rates of resistance to fluoroquinolones and trimethoprim-sulfamethoxazole approached 30%. Rates of resistance to nitrofurantoin, antipseudomonal penicillin/β-lactamase inhibitors, and carbapenems remained less than 10%. The percentage of isolates that were considered multidrug resistant varied (4% to 37%), depending on the definitions used.
Pharmacodynamics of Finafloxacin, Ciprofloxacin, and Levofloxacin in Serum and Urine against TEM- and SHV-Type Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae Isolates from Patients with Urinary Tract Infections
Authors: Dalhoff A. , Schubert S. , Vente A.
Published: February 2017

The pharmacodynamics of finafloxacin, ciprofloxacin, and levofloxacin against extended-spectrum-β-lactamase (ESBL)-producing
Enterobacteriaceae
isolates were compared. Since quinolones lose activity in acidic media, and particularly in urine, their activities were tested in parallel under conventional conditions and in acidic artificial urine. For this purpose, TEM- and SHV-type ESBL-producing
Escherichia coli
and
Klebsiella pneumoniae
strains and their wild-type counterparts were exposed in a modified Grasso model to simulated concentrations of drugs in serum and urine following oral doses of either finafloxacin at 800 mg once a day (q.d.), immediate-release ciprofloxacin at 500 mg twice a day (b.i.d.), extended-release ciprofloxacin at 1,000 mg q.d., or levofloxacin at 500 or 750 mg q.d. The concentrations of the drugs in urine were fitted by compartmental modeling. Bacteria were cultivated in Mueller-Hinton broth (MHB) at pH 7.2 or 5.8 or in artificial urine at pH 5.8. Bacteria were counted every 2 h until 10 h and at 24 h; the areas under the bacterial-count–versus–time curves were calculated. It was found that finafloxacin eliminated all strains within 2 h under all the conditions studied. At all doses studied, ciprofloxacin and levofloxacin were highly active against wild-type strains in MHB at pH 7.2 but lost activity in MHB, and particularly in urine, at pH 5.8. Viable counts of ESBL producers were reduced for 6 to 8 h by 3 log
10
titers, but the bacteria regrew thereafter. Ciprofloxacin and levofloxacin were almost inactive against the SHV producer grown in artificial urine. We conclude that pharmacodynamic models using artificial urine may mirror the physiology of urinary tract infections more closely than those using conventional media. In contrast to ciprofloxacin and levofloxacin, finafloxacin gained activity in this model at an acidic pH, maintained activity in artificial urine, and was active against TEM and SHV producers.
Characterization of the pJB12 Plasmid from Pseudomonas aeruginosa Reveals Tn
6352
, a Novel Putative Transposon Associated with Mobilization of the
bla
VIM-2
-Harboring In58 Integron
Authors: Botelho João , Grosso Filipa , Peixe Luísa
Published: February 2017

The
bla
VIM-2
-carrying In58 integron has been linked to a chromosomal location in different bacterial species, including
Pseudomonas aeruginosa
. This work reports the first fully sequenced In58-harboring plasmid, which is significantly different from the two previously identified
bla
VIM-2
-carrying plasmids in
P. aeruginosa
.
bla
VIM-2
might have been acquired by transposition of Tn
6352
, a novel transposon composed of the In58 and IS
Pa17
elements. The recognition of similar inverted repeat (IR) sites by IS
Pa17
reveals a common mobilization process associated with acquisition of the
bla
VIM-2
and
bla
VIM-1
genes.
In Vitro
Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir
Authors: Ng Teresa I. , Krishnan Preethi , Pilot-Matias Tami , Kati Warren , Schnell Gretja , Beyer Jill , Reisch Thomas , Lu Liangjun , Dekhtyar Tatyana , Irvin Michelle , Tripathi Rakesh , Maring Clarence , Randolph John T. , Wagner Rolf , Collins Christine
Published: February 2017

Pibrentasvir (ABT-530) is a novel and pan-genotypic hepatitis C virus (HCV) NS5A inhibitor with 50% effective concentration (EC
50
) values ranging from 1.4 to 5.0 pM against HCV replicons containing NS5A from genotypes 1 to 6. Pibrentasvir demonstrated similar activity against a panel of chimeric replicons containing HCV NS5A of genotypes 1 to 6 from clinical samples. Resistance selection studies were conducted using HCV replicon cells with NS5A from genotype 1a, 1b, 2a, 2b, 3a, 4a, 5a, or 6a at a concentration of pibrentasvir that was 10- or 100-fold over its EC
50
for the respective replicon. With pibrentasvir at 10-fold over the respective EC
50
, only a small number of colonies (0.00015 to 0.0065% of input cells) with resistance-associated amino acid substitutions were selected in replicons containing genotype 1a, 2a, or 3a NS5A, and no viable colonies were selected in replicons containing NS5A from other genotypes. With pibrentasvir at 100-fold over the respective EC
50
, very few colonies (0.0002% of input cells) were selected by pibrentasvir in genotype 1a replicon cells while no colonies were selected in other replicons. Pibrentasvir is active against common resistance-conferring substitutions in HCV genotypes 1 to 6 that were identified for other NS5A inhibitors, including those at key amino acid positions 28, 30, 31, or 93. The combination of pibrentasvir with HCV inhibitors of other classes produced synergistic inhibition of HCV replication. In summary, pibrentasvir is a next-generation HCV NS5A inhibitor with potent and pan-genotypic activity, and it maintains activity against common amino acid substitutions of HCV genotypes 1 to 6 that are known to confer resistance to currently approved NS5A inhibitors.
Insight into the Diversity of Penicillin-Binding Protein 2x Alleles and Mutations in Viridans Streptococci
Authors: van der Linden Mark , Otten Julia , Bergmann Carina , Latorre Cristina , Liñares Josefina , Hakenbeck Regine
Published: February 2017

The identification of commensal streptococci species is an everlasting problem due to their ability to genetically transform. A new challenge in this respect is the recent description of
Streptococcus pseudopneumoniae
as a new species, which was distinguished from closely related pathogenic
S. pneumoniae
and commensal
S. mitis
by a variety of physiological and molecular biological tests. Forty-one atypical
S. pneumoniae
isolates have been collected at the German National Reference Center for Streptococci (GNRCS). Multilocus sequence typing (MLST) confirmed 35 isolates as the species
S. pseudopneumoniae
. A comparison with the
pbp2x
sequences from 120 commensal streptococci isolated from different continents revealed that
pbp2x
is distinct among penicillin-susceptible
S. pseudopneumoniae
isolates. Four penicillin-binding protein x (PBPx) alleles of penicillin-sensitive
S. mitis
account for most of the diverse sequence blocks in resistant
S. pseudopneumoniae
,
S. pneumoniae
, and
S. mitis
, and
S. infantis
and
S. oralis
sequences were found in
S. pneumoniae
from Japan. PBP2x genes of the family of mosaic genes related to
pbp2x
in the
S. pneumoniae
clone Spain
23F
-1 were observed in
S. oralis
and
S. infantis
as well, confirming its global distribution. Thirty-eight sites were altered within the PBP2x transpeptidase domains of penicillin-resistant strains, excluding another 37 sites present in the reference genes of sensitive strains. Specific mutational patterns were detected depending on the parental sequence blocks, in agreement with distinct mutational pathways during the development of beta-lactam resistance. The majority of the mutations clustered around the active site, whereas others are likely to affect stability or interactions with the C-terminal domain or partner proteins.
Structural Analysis of Mycobacterium tuberculosis Homologues of the Eukaryotic Proteasome Assembly Chaperone 2 (PAC2)
Authors: Bai Lin , Jastrab Jordan B. , Isasa Marta , Hu Kuan , Yu Hongjun , Gygi Steven P. , Darwin K. Heran , Li Huilin
Published: February 2017

A previous bioinformatics analysis identified the
Mycobacterium tuberculosis
proteins Rv2125 and Rv2714 as orthologs of the eukaryotic proteasome assembly chaperone 2 (PAC2). We set out to investigate whether Rv2125 or Rv2714 can function in proteasome assembly. We solved the crystal structure of Rv2125 at a resolution of 3.0 Å, which showed an overall fold similar to that of the PAC2 family proteins that include the archaeal PbaB and the yeast Pba1. However, Rv2125 and Rv2714 formed trimers, whereas PbaB forms tetramers and Pba1 dimerizes with Pba2. We also found that purified Rv2125 and Rv2714 could not bind to
M. tuberculosis
20S core particles. Finally, proteomic analysis showed that the levels of known proteasome components and substrate proteins were not affected by disruption of Rv2125 in
M. tuberculosis
. Our work suggests that Rv2125 does not participate in bacterial proteasome assembly or function.

IMPORTANCE
Although many bacteria do not encode proteasomes,
M. tuberculosis
not only uses proteasomes but also has evolved a posttranslational modification system called pupylation to deliver proteins to the proteasome. Proteasomes are essential for
M. tuberculosis
to cause lethal infections in animals; thus, determining how proteasomes are assembled may help identify new ways to combat tuberculosis. We solved the structure of a predicted proteasome assembly factor, Rv2125, and isolated a genetic Rv2125 mutant of
M. tuberculosis
. Our structural, biochemical, and genetic studies indicate that Rv2125 and Rv2714 do not function as proteasome assembly chaperones and are unlikely to have roles in proteasome biology in mycobacteria.
Small lymphocytic lymphoma with Reed Sternberg cells: a diagnostic dilemma
Authors: Pervez S , Abro B , Shahbaz H
Published: February 2017

Reed Sternberg (RS) cells in the setting of small lymphocytic lymphoma (SLL) can complicate the histopathological diagnosis. We report a case of a man aged 54 years who presented with cervical lymphadenopathy. Resection of the lymph node was performed and sent for histopathological evaluation to a local laboratory. A diagnosis of SLL with Classic Hodgkin's lymphoma (CHL) was made. The medical oncologist who encountered this diagnosis for the first time sent the biopsy blocks to our laboratory for a second opinion. On review of the biopsy and immunohistochemical stains, it showed typical SLL morphology and immunophenotype. Focally, it showed large mononuclear RS type cells; however, no typical background of CHL was seen. The diagnosis was revised to ‘SLL with RS like cells with no convincing evidence of CHL’. The patient was subsequently treated as a case of SLL and no progression was observed on a follow-up of 5 years.
Cor triatriatum sinistrum: presentation of syncope and atrial tachycardia
Authors: Avari Malcolm , Nair Sunil , Kozlowska Zofia , Nashef Samer
Published: February 2017

We present a rather unusual cause for syncope associated with atrial tachycardia. A man aged 39 years presented with an episode of syncope and narrow complex tachycardia. Further investigations, including transoesophageal echocardiography, identified cor triatriatum sinistrum (CTS), a rare congenital abnormality characterised by the atrium being divided by a fibrous membrane. Although it is rare, there has been an increase in diagnosis due to developments in diagnostic imaging techniques. Symptoms are related to the size of fenestrations within the fibrous membrane. Presenting symptoms can mimic those seen in mitral stenosis. It is a condition that can occur in isolation, but it can also be associated with other cardiac abnormalities such as an atrial septal defect (ASD) (as in this case). Surgery is the definitive treatment (this man had surgical repair of CTS and closure of ASD) and should be considered at any age if there are any associated symptoms or complications.
Paget's disease of the anus masking a mixed adenoneuroendocrine tumour of the rectum
Authors: Ebrom Pierson , Parizh David , Hajdu Cristina H , Gadangi Pratap
Published: February 2017

A man aged 83 years with vague perirectal symptoms had a delayed diagnosis of Paget's disease of the anus. A lack of thorough digital rectal examination failed to diagnose a mixed adenonueroendocrine tumour of the rectum in a timely matter.
PHARMACOKINETICS OF RIFABUTIN IN COMBINATION WITH LOPINAVIR-RITONAVIR IN ADULT PATIENTS WITH HIV AND TUBERCULOSIS CO-INFECTION IN BURKINA FASO
Authors: Ouedraogo Henri Gautier , Matteelli Alberto , Regazzi Mario , Tarnagda Grissoum , Villani Paola , Sulis Giorgia , Diagbouga Serge , Roggi Alberto , Giorgetti Francesco , Kouanda Seni
Published: February 2017

Background

This study aimed to assess the pharmacokinetic profile of rifabutin (RBT) given at 150 mg or 300 mg every other day (EOD) in tuberculosis (TB)-HIV co-infected adult patients.

Methods

This is a pharmacokinetic prospective, pilot, open, randomised study of two doses of RBT in combination with lopinavir/ritonavir among HIV−TB patients in Burkina. Sixteen patients were randomised in two arms: TB treatment consisting HZE standard doses in association with RBT150 mg EOD (arm A, 8 patients) or RBT300 mg EOD (arm B, 8 patients) in combination with lopinavir/ritonavir. RBT plasma concentrations were evaluated after two weeks of combined HIV and TB treatment. Samples were collected at pre-dosing and at 1, 2, 3, 4, 6, 8 and12 hours after drug ingestion to measure plasma drug concentration using HPLC–MS/MS assay.

Results

The mean Cmax and AUC in the RBT 150 mg arm (Cmax=0.35±0,18 µg/mL, AUC(0–24)=3.94±2,1 µg.h/mL) were significantly lower (p=0.01) than those of the RBT 300 mg arm (Cmax=0.75±0.54 µg/mL AUC(0–24)=7.1±2.7 µg.h/mL). There was no significant difference in Tmax (Tmax=3.44±2.01 hoursvsTmax=3.86±2.04 hours) p=0.687. RBT follows linear kinetics and no significant differences were apparent in the mean oral clearance (CL/F) estimates (p=0.683), which were dose independent and similar for the 2 assessment doses. Five of 8 patients in RBT150 mg arm had a Cmax below plasma therapeutic limit (<0.3 µg/ml). All patients in RBT 300 mg arm had a higher Cmax than this limit. Also, at 48 hours of drug ingestion, all patients in the RBT 300 mg arm (8/8) had a mycobacterial minimum inhibitory concentration (MIC) above the limit (>0.06 µg/mL) compared with 4 of 8 patients in the RBT150 mg arm. The means Cmax, AUC (0–24) and Tmax of 25-O-desacetyl rifabutin of the RBT 300 mg arm were increased by 100% and 50% respectively compared to the RBT150 mg arm.

Conclusions

This study confirmed that the dose of rifabutin 150 mg three times a week in combination with lopinavir/ ritonavir is inadequate and could lead to the selection of rifamycin-resistant mycobacteria.
HEPATITIS B VIRUS CO-INFECTION IS ASSOCIATED WITH INCREASED ALL-CAUSE MORTALITY AMONG HIV-INFECTED ADULTS ON TENOFOVIR-DISOPROXIL-FUMARATE CONTAINING ANTIRETROVIRAL THERAPY IN LUSAKA, ZAMBIA
Authors: Vinikoor Michael , Chilengi Roma , Mulenga Lloyd , Kaayunga Callistus , Zyambo Zude , Davies Mary-Ann , Egger Matthias , Wandeler Gilles
Published: February 2017

Methods

We prospectively enrolled HIV-infected treatment naïve adults in Lusaka, Zambia. At enrolment, we recorded patient's demographics, body mass index (BMI), WHO clinical stage, CD4+ count, and hepatitis B surface antigen (HBsAg) status. In HBsAg-positive patients we measured HBV viral loads (VL; Roche, COBAS® AmpliPrep/COBAS® Taqman® Assay, Pleasanton, California). We defined active HBV co-infection as having an HBV VL320 IU/ml. TDF-based ART was the preferred first-line regimen. Follow-up visits occurred per national guidelines and we used phone and community tracing to optimise retention. Deaths were ascertained by clinic, family member, or community health worker report and losses to follow-up (LFTU) were defined as absences from clinic for 6+ months. Using multivariable Cox regression, we assessed the mortality risk among patients with HBV co-infection, adjusting for age, sex, WHO stage, BMI, and CD4+ count.

Results

During 2013–2014, 822 patients were enrolled and analysed at 1 year after ART initiation. Among this group, 438 (53.1%) were women, median age was 34 years (interquartile range, 29–40), 367 (44.8%) had WHO stage 3 or 4, 229 (28.2%) had BMI <18.5, and median baseline CD4+ 224 cells/ mm3. Of 126 HBsAg-positive individuals, 81 had active HBV infection. During the first year on ART, 48 patients died, 19 transferred out or withdrew, and 52 were LTFU. Those with HBV co-infection had twice the risk of death (adjusted hazard ratio, 2.23, 95% CI: 1.07–4.65) after adjustment for covariates.

Conclusions

In Southern Africa, HBV co-infection is a mortality risk factor and these patients should be diagnosed and those with replicating virus may need closer monitoring. Further investigation of the causes of death in HIV-HBV patients is needed.
CAN HIV TREATMENTS INFORM OTHER CONTEXTS? A TRIAL OF AN ADDITIONAL INDICATION FOR CO-TRIMOXAZOLE PROPHYLAXIS
Authors: Ngari Moses , Thitiri Johnstone , Mwalekwa Laura , Fegan Greg , Berkley James
Published: February 2017

Background

Co-trimoxazole prophylaxis is part of HIV management of opportunistic infections. However, it is not known if co-trimoxazole prophylaxis can prevent opportunistic infections among other vulnerable population such as people with complicated severe acute malnutrition (SAM). It is unclear if and how nutritional recovery may reduce susceptibility to infectious diseases like pneumonia with co-trimoxazole prophylaxis. We share secondary analysis results of multicentre, double-blinded, randomised clinical trial (ClinicalTrials. gov, numberNCT00934492) of daily co-trimoxazole prophylaxis among HIV non-infected children with SAM in Kenya.

Methods

We recruited 1781 hospitalised SAM children and randomised to either daily co-trimoxazole prophylaxis or matching placebo for six months and followed up for 12 months. Our outcome of interest was risk of subsequent pneumonia after index admission discharge, defined using the WHO guidelines. To determine changing susceptibility after discharge, cox regression model with monthly weight-for-height and height-for-age z-scores as time-varying covariates were used to identify risk factors of developing pneumonia.

Results

Overall, 257 children died, 122 (14%) among the co-trimoxazole group and 135 (15%) of placebo group; Hazard ratio (HR) 0.90 (95% CI: 0.71−1.16, p=0.43). There were 1257 episodes of pneumonia, 603 (21%) among co-trimoxazole group and 654 (22%) among placebo; HR 0.93 (95% CI:0.79−1.08, p=0.34) during 1556.6 child-years of observation (cyo). The monthly incidence rate for pneumonia and severe pneumonia declined over time (p=0.002 & p=0.001). Young age, urban residence, index admission with clinical signs of rickets and severe pneumonia, were associated with subsequent pneumonia. Index admission with diarrhoea and monthly weight-for-length z-score had protective effect. Protective effect of improving monthly anthropometric measures were evident from month two onwards. Proportion of pneumonia progressing to severe form declined with time (p=0.01) but there was no evidence case fatality ratios changed over time (p=0.41).

Conclusions

Improving nutritional status during recovery correlates directly with reduced susceptibility, but not with case fatality of pneumonia.
PREVALENCE AND PREDISPOSING FACTORS TO INTESTINAL PARASITIC INFECTIONS IN HIV/AIDS PATIENTS IN FAKO DIVISION OF CAMEROON
Authors: Nsagha Dickson
Published: February 2017

Background

Understanding the epidemiology of intestinal parasitic infections is essential for the effective management of HIV infection in areas where intestinal parasites are also endemic. Data on the prevalence of intestinal parasitic infections in people living with HIV/AIDS in Cameroon are scarce. This study was designed to determine the prevalence of intestinal parasitic infections, as well as assess the predisposing factors for the infections in HIV/AIDS patients in Fako division of Cameroon.

Methods

Stool specimen was collected from consented participants and examined for ova, cysts, larvae or oocytes using the Kato-Katz, Formalin-Ether Concentration, Modified Ziehl-Neelsen and Modified field staining techniques. Statistical analyses performed included the Chi-square test and logistic regression.

Results

At the end of the study, 300 participants were enrolled, the majority being females 236 (78.6%). The participants were between 21–70 years (mean±SD=40±10) of age. The overall prevalence of intestinal parasites was 82.6% (95% CI: 78.4–87.0). The prevalence of infection was associated with age, being more prevalent in the age group 51–60 years (p=0.032). Intestinal protozoa were more prevalent than intestinal helminthes (74.3%vs11.3%). The parasites isolated included:Cryptosporidium parvum(44.0%),Blastocystis hominis(25.0%),Microsporidium spp.(21.0%),Entamoeba histolytica(7.3%),Ascaris lumbricoïdes(4.3%),Isospora belli(4.3%),Trichuris trichiura(2.3%), hookworm (2.7%),Hymenolepis nana(1.3%),Strongyloïdes stercoralis(0.7%),Cyclospora cayetatensis(3.7%) andGiardia lamblia(3.3%). The predisposing factors for infection with intestinal parasites included poor educational background (OR=0.33, p=0.02), unskilled worker (OR=0.27, p=0.04), a well as source of drinking water (OR=2.6, p=0.03), and living with cats as pets (OR=3.06, p=0.01).

Conclusions

A very high prevalence of intestinal parasitic infections was observed in people living with HIV/AIDS. Routine screening for intestinal parasites should be instituted as part of HIV care in Fako division of Cameroon to improve the management of HIV/AIDS.
FACTORS AFFECTING ANTIRETROVIRAL DRUG ADHERENCE AMONG HIV ADULT PATIENTS ATTENDING HIV CLINIC AT THE UNIVERSITY TEACHING HOSPITAL IN LUSAKA
Authors: Chirwa Uchizi , Michelo Charles , Dambe Rosalia , Hamoonga Raymond
Published: February 2017

Background

Effectiveness of anti-retroviral therapy (ART) requires strict adherence. Adherence ≥95% achieves optimum therapeutic levels and reduces drug resistance. We sought to determine factors associated with ART adherence within the context of patient demographics and factors, and explore care treatment and support strategies used by patients and health workers.

Methods

A Mixed Method Sequential Explanatory Design (MMSED) was employed to study adult patients receiving ART from the University Teaching Hospital, Lusaka. Adherence was measured by missed clinic appointments and pharmacy collections over the last six months. The quantitative method assessed 715 complete pharmacy records extracted from the dispensing tool to ascertain demographic and patient factors. Bivariate and multivariate logistic regression analysis was employed. Qualitative research involved in-depth interviews with patients and key informants.

Results

Results showed 79.4% of the patients were adherent to clinical appointments while 46.3% were adherent to pharmacy refills. Multivariate analysis showed lower adherence amongst the widowed on clinical appointments (OR=0.3; 95% CI: 0.1–0.9). The stepwise regression analysis revealed significant factors for adherence on clinical appointment and pharmacy refills for widowed, co-habiting and no education, (p=0.008, p=0.044, and p=0.018), respectively. About 80% of patients interviewed were adherent to ART.

Conclusions

The results show moderate ART adherence (80%). However, in view of the identified factors affecting adherence, concerted and collaborative efforts through effective and efficient interventions are needed to improve the adherence levels to at least ≥95%.
IMPROVING TUBERCULOSIS SCREENING AND DIAGNOSIS AMONG PEOPLE WITH HIV: UPDATES FROM THE INTENSIFIED CASE FINDING STUDY IN KISUMU COUNTY, KENYA
Authors: Wandiga Steve , Oduor Patience , Agaya Janet , Okumu Albert , Sharma Aditya , Cavanaugh Sean , Cain Kevin
Published: February 2017

Background

Tuberculosis (TB) is the leading opportunistic infection and cause of death among people living with HIV (PLHIV). HIV predisposes latently TB-infected people to developing TB disease. Current TB screening algorithms lack sensitivity and specificity. We sought to determine the sensitivity and specificity of conducting a two-step clinical screening and testing for latent TB infection (LTBI).

Methods

We enrolled 650 newly diagnosed HIV patients aged >7 years from HIV clinics in Kisumu County, Kenya. Study participants were screened for TB symptoms and sputum tested for smear microscopy, liquid culture and GeneXpert MTB/RIF (Xpert). Quantiferon (QFT) and tuberculin skin testing (TST) for LTBI. Positive results from liquid culture or Xpert defined a TB case. ‘Negative for TB’ was any participant with at least two negative Xpert or culture results from different specimens. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated and compared for one – and two – stage screening and stratified by QFT results.

Results

Females were 62% of participants. TST-positive were 88 of 592 (15%); 274 of 648 (42%) were QFT-positive. TB prevalence was 15%. Screening results for one stage and second stage: 75% and 97% sensitivity, 31% and 12%, specificity, 89% and 96% NPV and 14% and 15% PPV, respectively. Screening performance stratified by QFT for sensitivity, specificity, NPV and PPV was 96%, 11%, 91% and 24% among QFT-positive.

Conclusions

Two-step versus one-step screening increases sensitivity but reduces specificity. Positive QFT result increases the PPV of two-step screening.
A REVIEW OF REGULATORY CAPACITY STRENGTHENING IN AFRICA IN HIV RESEARCH: THE NEED FOR A NEW PARADIGM
Authors: Fisher Kevin , Bahati Prince , Thyagarajan Bargavi
Published: February 2017

Background

Recent African initiatives suggest the need for new direction in capacity building and support for regulatory review of HIV prevention research. The African Vaccine Regulatory Forum recently harmonised practices to strengthen regulatory oversight and helped create the African Medicines Agency scheduled to be launched in 2018. The African Union, working through the New Partnership for Africa's Development, took a major step in 2016 adopting the African Union Model Law on Medical Product Regulation. These steps, as well as the work of the African Medicines Regulatory Harmonisation Programme, raise the question of how best to effect regulatory capacity building in this new environment.

Methods

This paper assesses the evolving role of support for African regulatory systems using a desk review of various regulatory strengthening activities currently underway or planned, with focus on Africa. This review was supplemented by interviews with key informants related to activities intended to support regulatory capacity building in low- and middle-income countries focused upon efforts that were of potential assistance to HIV vaccine development. This analysis supplements findings from a Regulatory Capacity Building Workshop held in Rwanda in 2015.

Results

External capacity building efforts need to be responsive to new and/or recent priorities and mechanisms by African entities regarding the strengthening and coordination of regulatory systems. Current capacity building efforts will benefit from coordination and information sharing geared toward new initiatives, as well as focus around ethics review.

Conclusions

Remarkable progress is being made towards the development of a safe and effective HIV prevention options, and several HIV vaccine efficacy trials are planned over the next few years. Recent ambitious African regulatory initiatives hold the potential to expedite review. It is time for capacity building efforts to consider how best to support the new coordinated and regional regulatory systems being developed and launched over the next few years.
PREVALENCE OF HBV, HIV, AND HIV-HBV CO-INFECTIONS AMONG HEALTHCARE WORKERS IN IBADAN, NIGERIA
Authors: Opaleye Oluyinka , Akanbi Olusola , Binuyo Michael
Published: February 2017

Background

HIV and HBV are endemic in Nigeria. HBV is globally the leading cause of death due to liver disease amongst HIV-infected persons. The study was done to ascertain the prevalence rate of HIV, HBV and HIV-HBV co-infections amongst health care workers in Ibadan, Nigeria.

Methods

A total of 217 healthcare workers working in large hospitals in Ibadan, Nigeria were signed up for the study. The socio-demographical data of the health care workers were collected using a questionnaire. HIV antibodies were evaluated using Stat Pak HIV test strips and HBV was evaluated using the ABON HBsAg test strips.

Results

There were 85 (39.2%) male and 132 (60.8%) female health care workers. Most were 21–35 years of age (109/217, 50.2%). Of the 217 health care workers 103(47.5%) and 21(9.7%) were positive for HBsAg and HIV, respectively, while 3(1.4%) had HIV-HBV co-infections. The prevalence of HBV infection was statistically significant (p<0.005) over HIV infection. Health care workers with ‘other’ level of education had the most predominant HBV prevalence (58/83, 69.9%, p=0.0267) while those with primary level of education had the highest HIV prevalence (2/12, 16.7%, p=0.0267. Females had the most predominant HBV (72/132, 54.5%) and HIV (17/132, 12.9%) (p=0.03). HIV was highest in age groups<20 years (2/16, 12.5%). Only widows/widowers (33.3%) had the highest HIV-HBV co-infection rates. Presence of tattoo in any part of the body, hepatitis B vaccination was significantly associated (p< 0.05) with HBV seropositivity among health care workers.

Conclusions

This study reveals a high prevalence of HIV, HBV and HIV-HBV co-infections among female health care workers. From our finding, the high infection rates of HBV and HIV noted amongst health care workers indicate the need to regularly screen this group for these viruses to reduce the further transmission of these viral infections.
DO XPERT MTB/RIF CYCLE THRESHOLD VALUES PROVIDE INFORMATION ABOUT PATIENT DELAYS FOR TUBERCULOSIS DIAGNOSIS?
Authors: Ssengooba Willy , Respeito Durval , Mambuque Edson , Blanco Silvia , Mandomando Inacio , Jong Bouke De , Cobelens Frank , Garcia-Basteiro Alberto
Published: February 2017

Background

Early diagnosis and initiation to appropriate treatment is vital for tuberculosis (TB) control. The Xpert MTB/RIF (Xpert) assay offers rapid TB diagnosis and quantitative estimation of bacterial burden through Cycle threshold (Ct) values. We assessed whether the Xpert Ct value is associated with delayed TB diagnosis as a potential monitoring tool for TB control programme performance.

Methods

This analysis was nested in a prospective study under the routine TB surveillance procedures of the National TB Control Program in Manhiça district, Maputo province, Mozambique. Presumptive TB patients were tested using smear microscopy and Xpert. We explored the association between Xpert Ct values and self-reported delay of Xpert-positive TB patients as recorded at the time of diagnosis enrolment. Patients with >60 days of TB symptoms were considered to have long delays.

Results

Of 1483 TB presumptive cases, 580 were diagnosed as TB of whom 505 (87.0%) were due to pulmonary TB and 302 (94.1%) were Xpert positive. Ct values (range, 9.7–46.4) showed a multimodal distribution. The median (IQR) delay was 30 (30–45) days. Ct values showed no correlation with delay (R2=0.001, p=0.621), nor any association with long delays: adjusted odds ratios (AOR) (95% CI) comparing to >28 cycles 0.99 (0.50–1.96; p=0.987) for 23–28 cycles, 0.93 (0.50–1.74; p=0.828) for 16–22 cycles; and 1.05 (0.47–2.36; p=0.897) for <16 cycles. Being HIV-negative (AOR [95% CI]), 2.05 (1.19–3.51, p=0.009) and rural residence 1.74 (1.08–2.81, p=0.023), were independent predictors of long delays.

Conclusions

Xpert Ct values were not associated with patient delay for TB diagnosis and cannot be used as an indicator of TB control program performance.