bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Clinical Experience with Famciclovir — A ‘Third Generation’ Nucleoside Prodrug
Authors: Chakrabarty Arun , Tyring Stephen K , Beutner Karl , Rauser Michael
Published: March 2015

The herpesviruses continue to produce considerable morbidity in man. Once infected with herpes simplex (HSV), the virus remains dormant within the nervous system and may reactivate if provoked by stress, trauma and/or other factors. To date, there is no cure, but antiviral medication can reduce duration and severity of symptoms and prophylaxis can suppress recurrent episodes of disease. The second-generation guanosine nucleosides, acyclovir and penciclovir, are effective inhibitors with low toxicity; both, however, have relatively low oral bioavailability. Subsequently, the orally bioavailable prodrugs valaciclovir and famciclovir have been introduced. These compounds offer high oral bioavailabilty and deliver acyclovir and penciclovir, respectively, to the target cells by means of more convenient dosing schedules. This short review points to recent experience with famciclovir in the management of HSV and varicella-zoster virus.
CCR5 Antagonists: Host-Targeted Antivirals for the Treatment of HIV Infection
Authors: Westby Mike , van der Ryst Elna
Published: March 2015

The human chemokine receptors, CCR5 and CXCR4, are potential host targets for exogenous, small-molecule antagonists for the inhibition of HIV-1 infection. HIV-1 strains can be categorised by co-receptor tropism — their ability to utilise CCR5 (CCR5-tropic), CXCR4 (CXCR4-tropic) or both (dual-tropic) as a co-receptor for entry into susceptible cells. CCR5 may be the more suitable co-receptor target for small-molecule antagonists because a natural deletion in the CCR5 gene preventing its expression on the cell surface is not associated with any obvious phenotype, but can confer resistance to infection by CCR5-tropic strains — the most frequently sexually-transmitted strains. The current leading CCR5 antagonists in clinical development include maraviroc (UK-427,857, Pfizer), aplaviroc (873140, GlaxoSmithKline) and vicriviroc (SCH-D, Schering-Plough), which have demonstrated efficacy and tolerability in HIV-infected patients. Pharmacodynamic data also suggest that these compounds have a long plasma half-life and/or prolonged CCR5 occupancy, which may explain the delay in viral rebound observed following compound withdrawal in short-term monotherapy studies. A switch from CCR5 to CXCR4 tropism occurs spontaneously in approximately 50% of HIV-infected patients and has been associated with, but is not required for, disease progression. The possibility of a co-receptor tropism switch occurring under selection pressure by CCR5 antagonists is discussed. The completion of ongoing Phase IIb/III studies of maraviroc, aplaviroc and vicriviroc will provide further insight into co-receptor tropism, HIV pathogenesis and the suitability of CCR5 antagonists as a potent new class of antivirals for the treatment of HIV infection.
Inhibition of Ganciclovir-Resistant Human Cytomegalovirus Replication by Kampo (Japanese Herbal Medicine)
Authors: Murayama Tsugiya , Yamaguchi Nobuo , Iwamoto Kozo , Eizuru Yoshito
Published: March 2015

We examined the effect of Kampo on the replication of ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) in the human embryonic fibroblast cell line MRC-5. Treatment of HCMV-infected cells with Sho-seiryu-to (SST; Xiao-Qing-Long-Tang in Chinese) resulted in the inhibition of viral replication without affecting the cell growth. SST treatment decreased the synthesis of viral DNA, but had no virucidal effect on cell-free HCMV. However, the inhibitory effect of SST on HCMV replication was ablated by anti-interferon-β (IFN-β) antibody suggesting that SST inhibits the replication of GCV-resistant HCMV through the induction of IFN-β. These results suggest that SST is a novel compund with potential as an anti-HCMV.
Elevated PrPC Expression Predisposes to Increased HSV-1 Pathogenicity
Authors: Thackray Alana M , Bujdoso Raymond
Published: March 2015

PrPC is a ubiquitously expressed glycophos-phatidylinositol-linked cell-surface glycoprotein found primarily in neural tissue. Although its normal function has not been established, there is evidence suggesting that PrPC is involved in cell signalling and cellular homeostasis. This suggests that variation in neuronal expression levels of this protein contributes towards pathogenicity induced by neurotropic agents. We have investigated the pathological response to infection with herpes simplex virus type-1 (HSV-1) in strains of mice that express different levels of PrPC. Prnp−/− mice fail to express PrPC due to an interruption in the open reading frame of the Prnp gene, whilst tg19 and tga20 mice express approximately 5 and 10 times more PrPC protein, respectively, than wild-type animals. Mice that express normal or increased levels of PrPC protein were more susceptible to acute HSV-1 infection than Prnp−/− mice. Following ear pinna inoculation with HSV-1 SC16, the order of susceptibility was tga20>tg19>wild-type> Prnp−/−. This trend was reversed when latent virus was assessed. Prnp−/− mice expressed significantly higher levels of latency-associated transcript-positive neurons in various tissues when compared with wild-type, tg19 and tga20 mice. Collectively, our data show that acute HSV-1 replication proceeds more efficiently in neuronal tissue that expresses PrPC protein and lends support to the view that this protein is involved in regulation of neurotropic viral pathogenesis. This suggests that interference of PrPC expression, or possible biochemical pathways associated with its function, may serve as an effective means of limiting the pathogenesis of acute HSV-1 infection.
Inhibition of Hepatitis C Replicon RNA Synthesis by β-D-2′-deoxy-2′-fluoro-2′-C-Methylcytidine: A Specific Inhibitor of Hepatitis C Virus Replication
Authors: Stuyver Lieven J , McBrayer Tamara R , Tharnish Phillip M , Clark Jeremy , Hollecker Laurent , Lostia Stefania , Nachman Tammy , Grier Jason , Bennett Matthew A , Xie Meng-Yu , Schinazi Raymond F , Morrey John D , Julander Justin L , Furman Phillip A , Otto Michael J
Published: March 2015

β-D-2′-Deoxy-2′-fluoro-2′- C-methylcytidine (PSI-6130) is a cytidine analogue with potent and selective anti-hepatitis C virus (HCV) activity in the subgenomic HCV replicon assay, 90% effective concentration (EC90)=4.6 +2.0 µM. The spectrum of activity and cytotoxicity profile of PSI-6130 was evaluated against a diverse panel of viruses and cell types, and against two additional HCV-1b replicons. The S282T mutation, which confers resistance to 2′- C-methyl adenosine and other 2′-methylated nucleosides, showed only a 6.5-fold increase in EC90. When assayed for activity against bovine diarrhoea virus (BVDV), which is typically used as a surrogate assay to identify compounds active against HCV, PSI-6130 showed no anti-BVDV activity. Weak antiviral activity was noted against other flaviviruses, including West Nile virus, Dengue type 2, and yellow fever virus. These results indicate that PSI-6130 is a specific inhibitor of HCV. PSI-6130 showed little or no cytotoxicity against various cell types, including human peripheral blood mononuclear and human bone marrow progenitor cells. No mitochondrial toxicity was observed with PSI-6130. The reduced activity against the RdRp S282T mutant suggests that PSI-6130 is an inhibitor of replicon RNA synthesis. Finally, the no-effect dose for mice treated intraperitoneally with PSI-6130 for six consecutive days was ≥100 mg/kg per day.
HIV Type-1 Latency: Targeted Induction of Proviral Reservoirs
Authors: Graci Jason D , Colacino Joseph M , Peltz Stuart W , Dougherty Joseph P , Gu Zhengxian
Published: March 2015

HIV type-1 (HIV-1) can establish a state of latency in infected patients, most notably in resting CD4+ T-cells. This long-lived reservoir allows for rapid re-emergence of viraemia upon cessation of highly active antiretroviral therapy, even after extensive and seemingly effective treatment. Successful depletion of such latent reservoirs is probably essential to ‘cure’ HIV-1 infection and will require therapeutic agents that can specifically and efficiently act on cells harbouring latent HIV-1 provirus. The mechanisms underlying HIV-1 latency are not well characterized, and it is becoming clear that numerous factors, both cell- and virus-derived, are involved in the maintenance of proviral latency. The interplay of these various factors in the context of viral reactivation is still poorly understood. In this article, we review the current knowledge regarding the mechanisms underlying maintenance of HIV-1 latency, both transcriptional and post-transcriptional, with a focus on potential targets that might be exploited to therapeutically purge latent proviral reservoirs from infected patients.
Synthesis and Anti-Human Immunodeficiency Virus Type 1 Integrase Activity of Hydroxybenzoic and Hydroxycinnamic Acid Flavon-3-yl Esters
Authors: Desideri N , Sestili I , Stein ML , Tramontano E , Corrias S , La Colla P
Published: March 2015

A series of new hydroxybenzoic and hydroxycinnamic acid flavon-3-yl esters were synthesized in order to obtain compounds targeting the human immunodeficiency virus (HIV) type 1 integrase (IN). The esters were tested for anti-IN and anti-reverse transcriptase (RT) activity in enzyme assays and for anti-HIV-1, anti-proliferative and anti-topoisomerase activity in cell-based assays. In enzyme assays, the two gallic acid flavon-3-yl esters showed a notable IN inhibition (IC50 values were 8.3 and 9.1 µM, respectively), while the two caffeic acid flavon-3-yl esters exhibited a modest activity (IC50 75 and 60 µM, respectively). Replacement of hydroxyl groups resulted in loss of potency. Caffeic acid 3′,4′-dichloroflavon-3-yl ester also inhibited the RT activity whereas it was not active on human topoisomerases. It therefore represents an interesting example of a compound specifically targeting more than one step of the virus replication cycle.
Human Immunodeficiency Virus Gene Regulation as a Target for Antiviral Chemotherapy
Authors: Daelemans Dirk , Vandamme Anne-Mieke , De Clercq Erik
Published: March 2015

Inhibitors interfering with human immunodeficiency virus (HIV) gene regulation may have great potential in anti-HIV drug (combination) therapy. They act against different targets to currently used anti-HIV drugs, reduce virus production from acute and chronically infected cells and are anticipated to elicit less virus drug resistance. Several agents have already proven to inhibit HIV gene regulation in vitro. A first class of compounds interacts with cellular factors that bind to the long terminal repeat (LTR) promoter and that are needed for basal level transcription, such as NF-κB and Sp1 inhibitors. A second class of compounds specifically inhibits the transactivation of the HIV LTR promoter by the viral Tat protein, such as the peptoid CGP64222. A third class of compounds prevents the accumulation of single and unspliced mRNAs through inhibition of the viral regulator protein Rev, such as the aminoglycosidic antibiotics. Most of these compounds have been tested in specific transactivation assays. Whether they are active at the postulated target in virus replication assays has, for many of them, not been ascertained. Toxicity data are often lacking or insufficient. Yet these data are crucial in view of the toxicity that may be expected for compounds that primarily interact with cellular factors. Although a promising lead, considerable research is still required before gene regulation inhibitors may come of age as clinically useful agents.
Fractions of Chemically Oversulphated Galactosaminoglycan Sulphates Inhibit Three Enveloped Viruses: Human Immunodeficiency Virus Type 1, Herpes Simplex Virus Type 1 and Human Cytomegalovirus
Authors: Di Caro A , Perola E , Bartolini B , Marzano M , Liverani L , Mascellani G , Benedetto A , Cellai L
Published: March 2015

A series of chemically oversulphated galactosaminoglycans (SO3H:COOH ratio ≥2) were tested in vitro as antiviral agents against human immunodeficiency virus type 1 (HIV-1), the aetio-logical agent of AIDS, and against herpes simplex virus type 1 and human cytomegalovirus, two agents responsible for opportunistic infections in HIV-infected people. The oversulphated derivatives displayed an increase in activity ranging from one to four orders of magnitude against the three viruses, as compared to the natural parent compounds (SO3H:COOH, ratio approx. 1). The antiviral activity of these polyanions appears to be favoured by a high degree of sulphation and a high molecular mass. An oversulphated dermatan, with a SO3H:COOH ratio of 2.86 and molecular mass of 23.2 kDa, was the most potent anti-HIV-1 compound (EC50 0.04 µg/ml). A second oversulphated dermatan, with a SO3H:COOH ratio of 2.40 and molecular mass of 25 kDa, displayed the highest activity against HSV-1 (EC50 0.01 µg/ml). An oversulphated chondroitin, with a SO3H:COOH ratio of 2.80 and molecular mass of 17.3 kDa, was the strongest anti-HCMV agent (EC50 0.4 µg/ml). In view of the absence of the side-effects typical of heparin-like compounds, a combination of these derivatives could have therapeutic potential.
Neuraminidase Inhibitors as Anti-Influenza Virus Agents
Authors: Kim Choung U , Chen Xiaowu , Mendel Dirk B
Published: March 2015

Influenza virus neuraminidase (NA) catalyses the cleavage of sialic acid residues terminally linked to glycoproteins and glycolipids and plays an important role in the replication of the virus. Recently, several potent NA inhibitors have been synthesized based on the rational design of mimicking the transition state of the sialic acid cleavage. Zanamivir and oseltamivir (GS 4104, the prodrug of GS 4071) have emerged as promising influenza NA inhibitors for the treatment and prophylaxis of human influenza virus infection. This review describes the recent work toward the discovery and development of influenza NA inhibitors.
Structure-Based Design of Non-Nucleoside Reverse Transcriptase Inhibitors of Drug-Resistant Human Immunodeficiency Virus
Authors: Mao Chen , Sudbeck Elise A , Venkatachalam TK , Uckun Fatih M
Published: March 2015

A computer model of reverse transcriptase (RT) from human immunodeficiency virus type 1 (HIV-1) was used to design thiourea compounds that were predicted to inhibit RT. The RT model was used to approximate how changes in binding pocket shape, volume and chemical properties resulting from residue mutations would affect inhibitor binding. Our lead compound, N-[2-(2,5-dime-thoxyphenylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea (HI-236) was tested against clinically observed non-nucleoside inhibitor (NNI)-resistant mutated strains of HIV. HI-236 was more potent than trovirdine, MKC-442 and zidovudine against the drug-sensitive HIV-1 strain IIIB, 50–100 times more effective than delavirdine or nevirapine and twice as effective as our recently reported lead compound N-[2-(2-fluorophenethyl)]-N′-[2-(5-bromopyridyl)]-thiourea (HI-240) against the NNI-resistant Y181C mutant HIV-1 strain A17. HI-236 was highly effective against the multidrug-resistant HIV-1 strain RT-MDR containing multiple mutations involving the RT residues 74V, 41L, 106A and 215Y. In general, thiourea compounds such as HI-236 and HI-240 showed better inhibition of drug-resistant strains of HIV-1 than thioalkylbenzyl-pyrimidine compounds such as HI-280 and HI-281. The improved activity of thioureas against RT mutants is consistent with a structural analysis of the NNI binding pocket model of RT. The activity of HI-236 against RT-MDR was superior to that of other anti-HIV agents tested, in the following order, from high to low activity; HI-236 (IC50 5 nM), HI-240 (IC50 6 nM), trovirdine (IC50 20 nM), zidovudine (IC50 150 nM), MKC-442 (IC50 300 nM), delavirdine (IC50 400 nM) and nevirapine (IC50 5 µM).
The privatisation of Australian electricity: Claims, myths and facts
Authors: Chester Lynne
Published: March 2015

Australia has one of the most ‘liberalised’ electricity sectors in the world. The sale of government-owned electricity companies has contributed to that liberalisation and a quarter of the proceeds of one of the world’s largest privatisation programmes. In 2014, the state governments of New South Wales and Queensland announced further electricity privatisations if re-elected. Advocates claim private ownership will mean more productive investment, lower costs leading to more efficient operations, lower prices for all consumers and better market functioning without government interference. Opponents contend that the true value of government businesses is not being realised at sale, retention can achieve returns greater than those from a sale, and that follow sale, prices will rise and jobs will be lost. This article demonstrates that the claims of either lower or higher prices, of job losses and of more efficient operations are tantamount to being myths of privatisation not borne out by reality.
Evaluation of three 5′ exonuclease–based real-time polymerase chain reaction assays for detection of pathogenic Leptospira species in canine urine
Authors: Fink Jamie M. , Moore George E. , Landau Ruth , Vemulapalli Ramesh
Published: March 2015

Leptospirosis is caused by several pathogenic Leptospira species, and is an important infectious disease of dogs. Early detection of infection is crucial for an effective antibiotic treatment of the disease. Though different polymerase chain reaction (PCR) assays have been developed for detection of pathogenic Leptospira spp., thorough evaluation of the performance of these assays using dog urine samples has not been carried out. In the current study, the performance of 3 real-time PCR (qPCR) assays was assessed, 1 targeting the 16S ribosomal RNA (rRNA) gene and the other 2 targeting the lipL32 gene, a gene for the LipL32 outer membrane protein. With DNA extracted from laboratory-cultured pathogenic Leptospira spp., all 3 qPCR assays showed 100% specificity and had identical lower limits of detection. Compared to a conventional, gel-based PCR assay, all 3 qPCR assays were 100-fold more sensitive. There was a 100% agreement in the results of the 3 assays when tested on urine samples collected aseptically from 30 dogs suspected for leptospirosis. However, when tested on 30 urine samples that were collected by the free-catch method, the 16S rRNA–based assay falsely detected 13.3% of the samples as positive for pathogenic Leptospira spp. Nucleotide sequence analysis of the amplified DNA fragments showed that the assay resulted in false positives because of unrelated bacteria. All urine samples collected from 100 apparently healthy dogs at a local animal shelter tested negative for pathogenic Leptospira spp. These results highlight the importance of sample-specific validation of PCR-based diagnostic assays and the application of appropriately validated assays for more reliable pathogen detection.
Development and use of a real-time polymerase chain reaction assay for the detection of Ophidiomyces ophiodiicola in snakes
Authors: Allender Matthew C. , Bunick David , Dzhaman Elena , Burrus Lucienne , Maddox Carol
Published: March 2015

Fungal pathogens threatening the conservation of wildlife are becoming increasingly common. Since 2008, free-ranging snakes across North America have been experiencing a marked increase in the prevalence of snake fungal disease associated with Ophidiomyces ophiodiicola. Diagnosis has historically relied on histology, microbiology, and conventional polymerase chain reaction (PCR). More sensitive methods are needed to adequately characterize the epidemiology. The current study describes the development of a real-time PCR (qPCR) assay for detecting a segment of the internal transcribed spacer 1 region between the 18S and 5.8S ribosomal RNA gene. The assay was able to detect as few as 1.05 × 101 gene copies per reaction. An additional 4 positive cases were detected when comparing a conventional PCR ( n = 3) and the qPCR ( n = 7) when used on swab samples from 47 eastern massasauga rattlesnakes. The newly developed assay is a sensitive and specific tool for surveillance and monitoring in the conservation of free-ranging snakes.
Cytologic findings and diagnostic yield in 92 dogs undergoing fine-needle aspiration of the pancreas
Authors: Cordner Amy P. , Sharkey Leslie C. , Armstrong P. Jane , McAteer Kaitlyn D.
Published: March 2015

The diagnosis of pancreatic disease in small animal veterinary patients is complicated by nonspecific clinical signs and the limitations of diagnostic testing. Pancreatic cytology is a potential diagnostic tool, but safety and diagnostic yield are not well characterized in large patient cohorts. We hypothesized that pancreatic fine-needle aspiration (FNA) in dogs would frequently generate diagnostic-quality samples and subsequent adverse medical events would be uncommon. Ninety-two client-owned dogs undergoing pancreatic FNA for clinical diagnostic evaluation were identified retrospectively by a computer search for pancreatic cytology submissions. Archived slides were reviewed by a single board-certified clinical pathologist using a predetermined descriptive scheme. Medical records were reviewed for adverse events 48 hr following FNA, for concurrent procedures and diagnosis in patients with adverse events and for histology results. Diagnostic yield was calculated as the % cases in which a cytologic diagnosis could be achieved; correlation with histology or other confirmatory testing was determined when possible. Diagnostic yield was 73.5%, and the major pathologic process identified cytologically correlated with confirmatory testing in 10 out of 11 cases. There were 7 adverse events, all in dogs with significant comorbidities or undergoing other invasive procedures. Pancreatic FNA in dogs has a good diagnostic yield and a low rate of clinical complications in a large case series of dogs. Correlation of cytology and histology results was high in a limited number of cases.
Acute phase proteins in healthy goats
Authors: Heller Meera C. , Johns Jennifer L.
Published: March 2015

Acute inflammatory processes can trigger increased production of acute phase proteins (APPs) that can be useful biomarkers of inflammation. APPs are diverse and include proteins involved in coagulation, opsonization, iron regulation, and limitation of tissue injury. Haptoglobin, serum amyloid A, and alpha-1 acid glycoprotein have been proposed as useful APPs in goats. APPs can differ markedly by species, therefore species-specific reference intervals and studies are necessary. The objective of this study was to determine species-specific reference intervals for 4 APPs in goats. Haptoglobin, serum amyloid A, lipopolysaccharide binding protein, and alpha-1 acid glycoprotein were measured in in 54 clinically normal adult goats. APPs were measured using goat-specific commercial enzyme-linked immunosorbent assay kits. Results were analyzed by 1-way analysis of variance to compare sexes and breeding status. Reference Value Advisor was used to calculate reference limits according to the IFCC-CLSI guidelines. Only 1 APP was found to vary in healthy animals; serum haptoglobin was increased in lactating animals and decreased in pregnant does in their second trimester when compared with open, nonlactating does. No sex-based differences were seen for any of the APPs measured. We report normal reference intervals for 4 serum APPs that may be useful as disease markers. Haptoglobin should be interpreted with caution in animals with unknown pregnancy status. Further studies are needed to determine whether these APPs are useful biomarkers in goat disease states.
Obesity Is Associated With Increased Complications After Operative Management of End-Stage Ankle Arthritis
Authors: Werner Brian C. , Burrus M. Tyrrell , Looney Austin M. , Park Joseph S. , Perumal Venkat , Cooper M. Truitt
Published: March 2015

Background:

Total ankle arthroplasty (TAA) and ankle arthrodesis (AA) are two operative options for the management of end-stage ankle arthritis that has failed conservative interventions. Obesity is associated with a greater incidence of musculoskeletal disease, particularly osteoarthritis of the weight-bearing joints, including the ankle. The objective of the present study was to use a national database to examine the association between obesity and postoperative complications after TAA and AA.

Methods:

The PearlDiver database was queried for patients undergoing AA and TAA using International Classification of Diseases, 9th Revision (ICD-9) procedure codes. Patients were divided into obese (body mass index ≥30 kg/m2) and nonobese (body mass index <30 kg/m2) cohorts using ICD-9 codes for body mass index and obesity. Complications within 90 days postoperatively were assessed using ICD-9 and Current Procedural Terminology (CPT) codes.

Results:

23,029 patients were identified from 2005 to 2011, including 5361 with TAA and 17,668 with AA. Obese TAA patients had a significantly increased risk of 90-day major, minor, local, systemic, venous thromboembolic, infectious, and medical complications compared with nonobese patients. The incidence of revision TAA was also significantly higher in obese patients compared with nonobese patients. Findings were similar for AA, as all types of complications were significantly higher in obese patients compared with nonobese patients.

Conclusion:

Obesity was associated with significantly increased rates of all complications after both TAA and AA. The cause of this association was likely multifactorial, including increased rates of medical comorbidities, intraoperative factors, and larger soft tissue envelopes.

Level of Evidence:

Level III, comparative series.
‘Look who’s talking now’: A taxonomy of speakers in single-turn political discourse
Authors: Wieczorek Anna E
Published: March 2015

The aim of this article is to propose a taxonomy of speakers from a socio-pragmatic perspective by taking an original approach to the study of single-turn political discourse, that is, political speeches, rather than debates, interviews or press conferences. This limitation on the scope of the study stems from the fact that the categorisation advanced is not concerned with turn-taking, but concentrates on the speaker’s use of other voices in his/her representation of reality. Thus, a clear distinction is made between the speaker and the sayer, namely the original speaker whose words are reported, or rather creatively reconstructed, by the current speaker ‘here and now’. The taxomony comprises a number of categories employed strategically by the current speaker in the service of different objectives. The speaker categories are inherently limited due to a single principle of categorisation: the form of the report. The singular speaker is the default type which enables the speaker to present himself/herself as an individual as well as his/her attitudes, values and beliefs, while the collective speaker enhances the speaker’s belonging to a group and allows him/her to speak on behalf of its members. The sayer categories, by contrast, are more varied due to three independent principles of categorisation: the form of the report, the genuineness of the sayer’s utterance and the number of accounts embedded in the narrating event. The approach taken to the analysis of the narrative passages that involve the proposed speaker types owes much to Chilton’s Discourse Space Theory and is concerned with conceptualisation of the speaker’s representation of events from chosen perspective(s). The corpus of speeches selected to investigate and illustrate individual categories consists of over 80 political speeches delivered by three Democratic American Presidents: John Kennedy, William Clinton and Barack Obama.
The negation of hierarchy and its consequences
Authors: Peacock Vita
Published: March 2015

This paper traces the large-scale abandonment of hierarchical models of society by human scientists in the aftermath of 1968. The late 20th century saw these scholars emphasizing the contractual and ‘egalitarian’ relations between actors, at the expense of relations predicated on status differences and the differentiation of function relative to a totality. It simultaneously argues that these scholarly developments hinged on a set of socio-economic conditions in Europe and the USA which defined ever-growing numbers of social forms in terms of the commodity. The great paradox, of course, is that the same historical moment in which the social was ‘flattened’ by human scientists also witnessed the emergence of new structural inequalities on an unprecedented scale. The paper concludes that this realization is leading to a resurgence of hierarchical models in the human sciences.
A study of scientific reasoning in a peripheral context: the discovery of the Raman Effect
Authors: Dasgupta Deepanwita
Published: March 2015

This paper is an attempt to reconstruct how C.V. Raman, a peripheral scientist in the early 20th century colonial India, managed to develop a research programme in physical optics from his remote colonial location. His attempts at self-training and self-education eventually led him to the discovery of the Raman Effect and to the Nobel Prize in Physics in 1930. In trying to re-construct an account of the ways in which Raman developed his research programme in optics by grasping various elements of a scientific practice from the Western scientific community, we see how a newcomer in science could be surprisingly creative in achieving new breakthroughs, and how through such efforts he or she can establish new trading zones with another established community that has the potential to develop into independent practices.
Oklahoma Retailers’ Perspectives on Mutual Benefit Exchange to Limit Point-of-Sale Tobacco Advertisements
Authors: Chan Andie , Douglas Malinda Reddish , Ling Pamela M.
Published: March 2015

Businesses changing their practices in ways that support tobacco control efforts recently have gained interest, as demonstrated by CVS Health’s voluntary policy to end tobacco sales. Point-of-sale (POS) advertisements are associated with youth smoking initiation, increased tobacco consumption, and reduced quit attempts among smokers. There is interest in encouraging retailers to limit tobacco POS advertisements voluntarily. This qualitative exploratory study describes Oklahoma tobacco retailers’ perspectives on a mutual benefit exchange approach, and preferred message and messenger qualities that would entice them to take voluntary action to limit tobacco POS advertisements. This study found that mutual benefit exchange could be a viable option along with education and law as strategies to create behavior change among tobacco retailers. Many retailers stated that they would be willing to remove noncontractual POS advertisements for a 6-month commitment period when presented with mutual exchange benefit, tailored message, and appropriate messenger. Mutual benefit exchange, as a behavior change strategy to encourage voluntary removal of POS tobacco advertisements, was acceptable to retailers, could enhance local tobacco control in states with preemption, and may contribute to setting the foundation for broader legislative efforts.
Identification of a dibenzocyclooctadiene lignan as a HIV-1 non-nucleoside reverse transcriptase inhibitor
Authors: Han Ying-Shan , Xiao Wei-Lie , Xu Hongtao , Kramer Victor G , Quan Yudong , Mesplède Thibault , Oliveira Maureen , Colby-Germinario Susan P , Sun Han-Dong , Wainberg Mark A
Published: March 2015

Background

Due to resistance to all classes of anti-HIV drugs and drug toxicity, there is a need for the discovery and development of new anti-HIV drugs.

Methods

HIV-1 inhibitors were identified and biologically characterized for mechanism of action.

Results

We identified a dibenzocyclooctadiene lignan, termed HDS2 that possessed anti-HIV activity against a wide variety of viral strains with EC50 values in the 1–3 µM range. HDS2 was shown to act as an NNRTI by qPCR and in vitro enzyme assays.

Conclusions

This compound provides a new scaffold for further optimization of activity through structure-guided design.
For a politics of atmospheric governance
Authors: Feigenbaum Anna , Kanngieser Anja
Published: March 2015

A rise in social science scholarship on atmospheres has raised questions on how to articulate complex material and imperceptible events and encounters. Responding to Peter Adey’s Air Affinities, this review proposes the need to traverse geopolitics and geopoetics to more fully engage these. Going further, it argues that such traversals are key to approaching specific situations and devices of what we call ‘atmospheric policing’. Exploring recent examples of tear gas and sound warfare deployment in occupied Palestine, the review shows how discourses on atmospheres may be used to bring accountability into ecologies of violence.
The condition of premodernity
Authors: Steinberg Philip E
Published: March 2015

In ‘Air’s Affinities’, Peter Adey (2015) adopts a premodern approach wherein an object’s elemental essence can be read directly from subjective encounter. This perspective effectively engages the material without endorsing determinism, the essential without endorsing the analytics of science and the power of the encounter without endorsing the radical subjectivity of phenomenology. However, it strips observation and analysis of its potential for critique, instead endorsing an outlook that is, at root, theological in its dependence on faith for understanding unobservable and unexplainable processes, elements, essences and affinities.
Effect of oral melatonin and wearing earplugs and eye masks on nocturnal sleep in healthy subjects in a simulated intensive care unit environment: which might be a more promising strategy for ICU sleep deprivation?
Authors: Huang Hua-Wei , Zheng Bo-Lu , Jiang Li , Lin Zong-Tong , Zhang Guo-Bin , Shen Ling , Xi Xiu-Ming
Published: March 2015

Introduction

Sleep deprivation is common in critically ill patients in the intensive care unit (ICU). Noise and light in the ICU and the reduction in plasma melatonin play the essential roles. The aim of this study was to determine the effect of simulated ICU noise and light on nocturnal sleep quality, and compare the effectiveness of melatonin and earplugs and eye masks on sleep quality in these conditions in healthy subjects.

Methods

This study was conducted in two parts. In part one, 40 healthy subjects slept under baseline night and simulated ICU noise and light (NL) by a cross-over design. In part two, 40 subjects were randomly assigned to four groups: NL, NL plus placebo (NLP), NL plus use of earplugs and eye masks (NLEE) and NL plus melatonin (NLM). 1 mg of oral melatonin or placebo was administered at 21:00 on four consecutive days in NLM and NLP. Earplugs and eye masks were made available in NLEE. The objective sleep quality was measured by polysomnography. Serum was analyzed for melatonin levels. Subjects rated their perceived sleep quality and anxiety levels.

Results

Subjects had shorter total sleep time (TST) and rapid eye movement (REM) sleep, longer sleep onset latency, more light sleep and awakening, poorer subjective sleep quality, higher anxiety level and lower serum melatonin level in NL night (P <0.05). NLEE had less awakenings and shorter sleep onset latency (P <0.05). NLM had longer TST and REM and shorter sleep onset latency (P <0.05). Compared with NLEE, NLM had fewer awakenings (P = 0.004). Both NLM and NLEE improved perceived sleep quality and anxiety level (P = 0.000), and NLM showed better than NLEE in perceived sleep quality (P = 0.01). Compared to baseline night, the serum melatonin levels were lower in NL night at every time point, and the average maximal serum melatonin concentration in NLM group was significantly greater than other groups (P <0.001).

Conclusions

Compared with earplugs and eye masks, melatonin improves sleep quality and serum melatonin levels better in healthy subjects exposed to simulated ICU noise and light.

Trial registration

Chinese Clinical Trial Registry ChiCTR-IPR-14005458. Registered 10 November 2014.
Socioeconomic and environmental effects of China’s Conversion of Cropland to Forest Program after 15 years: a systematic review protocol
Authors: Gutiérrez Rodríguez Lucas , Hogarth Nick , Zhou Wen , Putzel Louis , Xie Chen , Zhang Kun
Published: March 2015

Background

Agricultural activities on sloping lands have historically led to forest loss and degradation in China which, coupled with industrial pressures on the environment, were deemed responsible for catastrophic flooding events in the late 1990s. After these events, China’s forest policy underwent a significant reorientation towards ecological conservation and rural development, a process epitomized by the Conversion of Cropland to Forest Program (CCFP). Launched in 1999, the CCFP integrates both socioeconomic and environmental objectives with the aim of reforesting smallholder cropland on sloping lands, while compensating farmers with payments for their lost income. Following 15 years of implementation, it is timely to conduct a comprehensive assessment of the state of knowledge about the CCFP’s impacts on human populations and the environment.

Methods/design

The primary research question asks “What socioeconomic and environmental effects has the Conversion of Cropland to Forest Program had on human populations and land resources during its first 15 years in China?” We use a theory of change and a Population-Intervention-Comparator-Outcome (PICO) framework to structure our systematic review, where populations of interest consist of both human populations and land resources targeted by the program, while the intervention of interest is the CCFP as defined by its component activities, including compensatory subsidies, skill-training, and enforcement with field checks. Outcomes are defined as both the socioeconomic and environmental impacts of the program. We will conduct a search for relevant English and Chinese language literature on Scopus, Web of Science, CAB Abstracts, AGRIS (FAO), and the China National Knowledge Infrastructure. Search results will be screened for relevance in a two stage process (titles and abstracts, followed by full texts) based on predefined eligibility criteria, and then further assessed for potential sources of bias. Extraction of data from those studies that have passed full-text screening will follow a coding protocol based on the PICO framework, and quantitative and qualitative analyses of the extracted data will be conducted and synthesized. Finally, a narrative report will present the findings of the review, alongside a geographic map illustrating the coverage of included studies compared with the actual implementation area of the CCFP.
Increased susceptibility to otitis media in a Splunc1-deficient mouse model
Authors: Bartlett Jennifer A. , Meyerholz David K. , Wohlford-Lenane Christine L. , Naumann Paul W. , Salzman Nita H. , McCray Paul B.
Published: March 2015

Otitis media (inflammation of the middle ear) is one of the most common diseases of early childhood. Susceptibility to otitis is influenced by a number of factors, including the actions of innate immune molecules secreted by the epithelia lining the nasopharynx, middle ear and Eustachian tube. The SPLUNC1 (short palate, lung, nasal epithelial clone 1) protein is a highly abundant secretory product of the mammalian nasal, oral and respiratory mucosa that is thought to play a multifunctional role in host defense. In this study we investigated Splunc1 expression in the ear of the mouse, and examined whether this protein contributes to overall host defense in the middle ear and/or Eustachian tube. We found that Splunc1 is highly expressed in both the surface epithelium and in submucosal glands in these regions in wild-type mice. In mice lacking Splunc1, we noted histologically an increased frequency of otitis media, characterized by the accumulation of leukocytes (neutrophils with scattered macrophages), proteinaceous fluid and mucus in the middle ear lumens. Furthermore, many of these mice had extensive remodeling of the middle ear wall, suggesting a chronic course of disease. From these observations, we conclude that loss of Splunc1 predisposes mice to the development of otitis media. The Splunc1−/− mouse model should help investigators to better understand both the biological role of Splunc1 as well as host defense mechanisms in the middle ear.
Technological Approaches to Teaching Terminology
Authors: Брукс  , Bruks Elena
Published: March 2015

The article analyzes the technological approaches which are taking place in teaching foreign languages to students specialized in physics. The opinion of a number of researchers is reconsidered in the article. Special attention is paid to terminology and curriculum context to form a potential students’ vocabulary, where particular concepts are under critical rethinking. The author singles out methodological aims and objectives, as well as strategies in the students training, where an individual approach is the essence to the educational process. The author defines specifics in training and learning and, it’s from this point of view, the effectiveness and quality of education is studied. The article identifies directions for further research in the field of the language for professional needs.
Washing a patient's hair in bed: a care fundamental
Authors: Peate Ian
Published: March 2015

Assisting the patient to care for their hair and washing the hair are two skilled activities that the healthcare assistant and assistant practitioner (HCA and AP) will need to perform. Understanding the function of hair physiologically, as well as the significance of hair from a cultural and religious perspective, will mean the HCA and AP are considering the patient's needs from a holistic perspective.

This article provides the reader with an overview of personal hygiene, emphasising the fact that this activity of living is based on individual preference. There is a brief discussion of the anatomy of the skin and its ‘appendage’—the hair.

An overview of how to wash a patient's hair in bed is provided. When the HCA and AP perform this important activity, the overriding aim is to provide safe and effective care.
Mentors: supporting learning to improve patient care
Authors: Norman Kay , Roche Kairen
Published: March 2015

Mentorship is becoming an important aspect of professional development among all healthcare professionals. What was once understood as purely the domain of nurse registrants in teaching and assessing student nurses is now being considered to support healthcare assistants (HCAs) in their professional development. This article introduces some of the benefits of mentorship for HCAs and how this can ultimately improve care delivery.
Disability discrimination (6): a critique of equality and diversity legislation
Authors: Barber Chris
Published: March 2015

This article seeks to discuss the value and effectiveness of the Acts of Parliament and the Reports highlighted earlier in this series, specifically how effective were these Parliamentary Acts and independent Reports In tackling and preventing disability discrimination and to try and gauge whether these documents were ‘fit for purpose’.
New masculinities in Chinese and Japanese combat films
Authors: Weiss Amanda
Published: March 2015

Through an analysis of popular combat films and television shows, this article argues that there has been a transformation in the representation of the hero-soldier in both China and Japan. Using theories of masculinity and nationalism, it suggests that recent Chinese films reveal a turn towards hybrid heroism-victimhood, increased focus on the emasculation of Japanese soldiers, and tensions between the market and the state. Meanwhile, Japanese films illustrate continued differences between the ambiguous mainstream and the straightforward nationalism of the right, albeit with an overall trend towards the rehabilitation of the problematic image of the soldier. Such shifts in the imagining of the soldier-hero demonstrate the ways in which Chinese and Japanese discourses on national identity have changed over time.
Lisa Lu interview
Authors: Williams Tony
Published: March 2015

This interview covers the long career of veteran actress Lisa Lu Yan in American media and Chinese cinema. Lisa Lu began acting a decade after she relocated to America following the change of government in china. Thanks to Frank Borzage, she began her prolific career in American television and became the second Chinese actress in post-war cinema to co-star in The Mountain Road (1960) with James Stewart. Among the many well-known American television series she appeared in during the 1960s were Bonanza, Cimarron City, Checkmate, and Yancy Derringer. She also appeared alongside Richard Boone in the opening segements of Have Gun Will Travel for one season in the role of “Hey Girl”, one she made her own. She returned to Hong Kong to star in The Arch (1969), the first film directed by female director Tan Shu-shuan in 1969 and later appeared in The Shaw Brothers’ 14 Amazons (1971). Run Run Shaw then offered her the title role in Li Han-hsiang’s The Empress Dowager and its sequel. She later played the same role in the opening sequences of Bertolucci’s The Last Emperor. Since then, she has continued her prolific career working in film, screen, and stage in America, China, and Taiwan.
Book Review
Authors: Leary Charles
Published: March 2015

The Asian Cinema Experience: Styles, Spaces Theory, Stephen Teo (2013) London: Routledge, 269 pp., ISBN: 9780415571463, h/bk, £85
Problems with feminine empowerment in goddess films: A feminist analysis of South Indian goddess films
Authors: Sankaran Chitra
Published: March 2015

The goddess genre of films, popular in South India, has traditionally been conceived of as dedicated to presenting the glory and power of the Hindu goddess as divine mother, saviour and protector. The imaging of the goddess is interesting and unique in that it seems to stand outside the normal representations of women in (Indian) cinema. This has made it worthwhile to investigate this genre from the perspective of feminism. This study begins by discussing and demonstrating ways in which the goddess figure has been imaged in extra/ordinary ways to stand outside male scopic regimes. It then establishes how despite this supreme empowerment of the goddess within the filmic diegesis there is little concomitant empowerment of the mortal female. Finally, the study argues that in recent years even the empowerment of the goddess appears compromised.
Questions begin Where the Clouds End: Ethnic identity and the documentary ‘Voice’
Authors: Hasan Daisy
Published: March 2015

I interviewed Wanphrang Diengdoh about his most recent film, Where the Clouds End, in Shillong on the 15th of August 2014. This day is not only nationally significant but also politically fraught in north-east India. ‘Dissident’ outfits call for bandhs to protest against the Indian state while the regional state machinery mobilizes citizens to celebrate the day and defy the bandhs. Unlike earlier years, when people silently allied with the dissidents by remaining indoors, this time round there was public movement, even celebration, as restaurants offered reduced price menus and concerts were held in public squares. As the sun went down and dusk crept up over the hills and into the city, we gathered around my tape recorder. Clutching mugs of Sharawn tea, a delicately flavoured Khasi variety that is yet to be discovered by the rest of the world, we exchanged stories and discussed complex ideas. This article is based on that wide ranging conversation as well as my critical appraisal of the film.