bluuebunny/crossref_metadata_2025 huggingface dataset:
Valuing an Early‐Stage Biotechnology Investment as a Rainbow Option
Authors: Brous Peter A.
Published: July 2011

In an article published in this journal in 2003, Richard Shockley and three of his students presented a detailed valuation of an early‐stage biotechnology investment using a binomial lattice option pricing model. The article demonstrates how investments with multiple stages can be treated as “compound sequential options”—that is, as series of options in which investments in one option provide the opportunity to invest in the next in the series.

In this article, the author uses the same business case analyzed by Shockley et al. to demonstrate how to value this early‐stage biotechnology investment by separately modeling the two types of risks: technology and product market. An option that has two distinct kinds of risk that develop differently over time is known as a “rainbow option.” The key adjustment to the option pricing model required to value such an option is that, instead of the standard binomial option pricing model with two outcomes at each point in time, the author uses a “quadranomial” option pricing model with four outcomes at each point in time. By distinguishing technology risks from product market risks and allowing them to develop differently over time, the author's analysis leads to a very different valuation and, indeed, a different decision about the initial investment than the one produced by Shockley's model.
Terminal Value, Accounting Numbers, and Inflation
Authors: Friedl Gunther , Schwetzler Bernhard
Published: July 2011

In a 2008 article published in this journal, Michael Bradley and Gregg Jarrell argue that the well‐known Gordon‐Shapiro (henceforth “GS”) model for calculating terminal values does not properly account for the effects of inflation. Bradley and Jarrell suggest modifying the growth factor in the standard GS model by adding an additional term to the nominal growth rate that reflects the positive effect of inflation on the value of existing assets.

In this article, the authors support the original Gordon‐Shapiro method for calculating terminal values by showing what they believe to be an oversight of the Bradley‐Jarrell critique. According to the authors, the disagreement stems from the use of fundamentally different assumptions about the effect of inflation on the capital investment required to sustain a business. Although Bradley‐Jarrell agree with the authors that intrinsic value is the discounted value of future free cash flows, their assumptions about capital investment effectively lead them to conclusions similar to those practitioners who attempt to value companies on the basis of discounted future accounting earnings. Despite much common practice, the GS model was meant to be applied to free cash flows, not accounting earnings. And for companies with substantial capital investment, the differences between accounting earnings that involve accruals and free cash flows can be very large.
Coumarin‐Based Bioactive Compounds: Facile Synthesis and Biological Evaluation of Coumarin‐Fused 1,4‐Thiazepines
Authors: Khoobi Mehdi , Foroumadi Alireza , Emami Saeed , Safavi Maliheh , Dehghan Gholamreza , Alizadeh Babak H. , Ramazani Ali , Ardestani Sussan K. , Shafiee Abbas
Published: July 2011

As part of our ongoing studies on the synthesis of bioactive coumarin compounds, we synthesized a series of new coumarin‐fused 1,4‐thiazepines using a simple method. The biological activity of target compounds along with 3‐(2‐hydroxybenzylidene)chroman‐2,4‐dione intermediates was screened by evaluation of their antioxidant and cytotoxic activities. The antioxidant activity was assessed using two methods, namely, 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging method and ferric reducing antioxidant power (FRAP) assay. 4‐Methoxyphenolic compound 5d in thiazepine series showed the most potent scavenging activity, while the 4‐bromophenolic derivative 5b was the most efficient compound in FRAP assay. Also, the result of cytotoxic evaluation using MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide] assay demonstrated that compound 5b is at least twofold more potent than etoposide against MCF‐7, SK‐N‐MC, and MDA‐MB 231 cell lines.
Carotid Atherosclerotic Disease and Cognitive Function: Mechanisms Identifying New Therapeutic Targets
Authors: Balucani Clotilde , Silvestrini Mauro
Published: July 2011

The treatment of carotid atherosclerotic disease lies primarily in decreasing the risk of stroke. Many investigations have suggested carotid atherosclerotic disease as being independently associated with cognitive dysfunction, also supporting the notion that in sub-clinical stages, carotid atherosclerotic disease may not be truly silent. An improvement in cognitive function following revascularization approaches may be expected from the reduced embolism and the improved hemodynamics achieved. However, there are no strong data indicating a cognitive change after carotid angioplasty and stenting or carotid endarterectomy in patients who do not experience stroke complications and there is no evidence to support the performance of prophylactic revascularization procedures with the aim of preventing a cognitive decline in otherwise asymptomatic patients. Given the burden of dementia and its tragic implications for individuals and societies, the identification and treatment of such a preventable condition as carotid atherosclerotic disease should be considered. Therefore, it would be desirable in the design of future comparative studies of treatment strategies for carotid atherosclerotic disease to consider cognitive outcome as an endpoint.
Magnetic endoscopic imaging saves abdominal compression and patient pain in routine colonoscopies
Authors: DECHÊNE Alexander , JOCHUM Christoph , BECHMANN Lars P , WINDECK Susanne , GERKEN Guido , CANBAY Ali , ZÖPF Thomas
Published: July 2011

OBJECTIVE:  Magnetic endoscope imaging (MEI) is a technique for the direct visualisation of endoscope configuration within the colon. This method may prevent loop formation by giving visual feedback of endoscope movement. This study aimed to evaluate the efficacy of MEI in improving colonoscopy performance.

METHODS:  Overall 1000 consecutive patients who underwent a complete routine colonoscopy were randomized into two groups: in group A with MEI, while in group B without MEI. Sedation was performed according to local standards. In both groups time to reach the cecum, the number of positioning maneuvers and involvement of a second assistant nurse were recorded. Abdominal compression was graded from 1 to 4 according to the duration and intensity of compression was quantified using a scale from 1–3 according to compression form and patient reaction.

RESULTS:  Patients were randomized (group A with MEI, n = 490; group B without MEI, n = 510) and a total colonoscopy was performed. Time to cecal intubation did not differ between the groups (507 s vs 538 s; NS). The duration of abdominal compression was significantly shorter in MEI guided colonoscopy. The intensity of abdominal compression was lower in group A and fewer turn maneuvers needed per patient. A trend towards a reduced need for assistance in MEI group was seen.

CONCLUSION:  Although MEI does not generally accelerate colonoscope advancement, it significantly reduces the force and the duration of abdominal compression by assistant personnel, thus minimizing patient discomfort and decreasing the need for additional staff.
Economic burden attributable to functional bowel disorders in Iran: A cross‐sectional population‐based study
Authors: MOGHIMI‐DEHKORDI Bijan , VAHEDI Mohsen , POURHOSEINGHOLI Mohammad Amin , KHOSHKROOD MANSOORI Babak , SAFAEE Azadeh , HABIBI Manijeh , POURHOSEINGHOLI Asma , ZALI Mohammad Reza
Published: July 2011

OBJECTIVE:  While few population‐based studies on the economic burden of functional bowel disorders (FBD) have been published from developing countries like Iran, this study aimed to estimate their direct and indirect costs for five groups of patients: irritable bowel syndrome (IBS), functional constipation (FC), unspecified‐FBD (U‐FBD), functional abdominal bloating (FAB) and functional diarrhea (FD).

METHODS:  Up to 18 180 adults randomly sampled from Tehran, Iran (2006–2007) were interviewed using two questionnaires based on the Rome III criteria to detect FBD patients and to estimate their medical expenses (such as visiting the doctor, drugs, hospitalization and laboratory tests) and productivity loss in the previous 6 months. All costs were converted to dollar purchasing power parity (PPP$) to facilitate cross‐country comparisons.

RESULTS:  The mean total 6‐month costs were approximately: 160, 147, 103, 96 and 42 PPP$ for IBS, FC, U‐FBD, FAB and FD, respectively. The highest proportion of drug consumption was found in IBS patients. The highest mean duration of absence from work was seen in IBS patients (2.26 days). Overall, doctor visit costs accounted for approximately 1/3 of the total costs for FBD, followed by hospitalization. A higher indirect cost of illness was found in IBS (54 PPP$), whereas it was zero in FD.

CONCLUSION:  The economic burden of FBD seems to be moderately high in Iran and it imposes a relatively heavy financial burden on the Iranian national health system because of its high prevalence and its impact on quality of life, productivity and waste of resources.
Immunomodulation of inducible co‐stimulator (ICOS) in human cytokine‐induced killer cells against cholangiocarcinoma through ICOS/ICOS ligand interaction
Authors: HE Min , WANG Ying , SHI Wei Jin , WANG Shu Jun , SHA Hui Fang , FENG Jiu Xian , WANG Jian
Published: July 2011

OBJECTIVE:  To evaluate the immunomodulation of inducible co‐stimulator (ICOS) in cytokine‐induced killer (CIK) cells against cholangiocarcinoma.

METHODS:  CIK cells were generated from normal peripheral blood mononuclear cells. Methyl thiazolyl tetrazolium assay was performed to assess proliferation of CIK‐ICOS and controlled CIK cells; ELISA was used to analyze the expression of cytokines. Reverse transcription‐polymerase chain reaction and immunohistochemistry were performed to evaluate the expression of ICOS ligand (ICOSL) in CIK cells and human cholangiocarcinoma cell line QBC939 cells. The cytotoxicity of CIK cells was determined either by lactate dehydrogenase‐releasing assay in vivo or alteration of tumor size prior to and after the treatment of CIK cells in vivo.

RESULTS:  CIK‐ICOS cells proliferated more and expressed higher secretion a level of interferon‐γ than the controlled CIK. These cells exhibited higher cytotoxicity against cholangiocarcinoma cell lines at all efficacy: toxicity (E:T) ratios tested than the controlled CIK cells. More importantly, the anti‐ICOSL antibody was able to attenuate the elevated cytotoxicity mediated by ICOS overexpression. When injected into cholangiocarcinoma xenografts in severe combined immunodeficiency mice, CIK‐ICOS cells survived better than the controlled CIK cells around xenografts and significantly reduced the growth rate of cholangiocarcinoma, with least volume increase and more severe necrosis of the xenografts than controlled mice treated with saline, CIK or CIK‐enhanced green fluorescent protein.

CONCLUSION:  ICOS can enhance the cytotoxic effect of CIK cells against cholangiocarcinoma both in vitro and in vivo. This effect is mediated by ICOS‐augmented cytokine secretion and cell proliferation, and in part through ICOS‐ICOSL interaction.
Impacting Population Cardiovascular Health Through a Community‐Based Practice Network: Update on an ASH‐Supported Collaborative
Authors: Egan Brent M. , Laken Marilyn A. , Shaun Wagner C. , Mack Sheryl S. , Seymour‐Edwards Kim , Dodson John , Zhao Yumin , Lackland Daniel T.
Published: July 2011

J Clin Hypertens (Greenwich). 2011;13:543–550. ©2011 Wiley Periodicals, Inc.

The Hypertension Initiative began in 1999 to help transition South Carolina from a leader in cardiovascular disease (CVD) to a model of heart and vascular health. Goals were to reduce heart disease and stroke by 50% by promoting healthy lifestyles and access to effective care and medications. Continuing medical education was used to train providers, encourage physicians to become American Society of Hypertension (ASH)–certified hypertension specialists and recruit practices into the community‐based practice network (CBPN). Practice data audit with provider specific feedback is a key quality improvement tool. With ASH support, the CBPN has grown to 197 practices with approximately 1.6 million patients (approximately 700,000 hypertensives). Clinical data are obtained from electronic health records and quarterly provider feedback reports are generated. Hypertension, hypercholesterolemia, and diabetes control rose and South Carolina’s ranking improved from 51st to 35th in CVD mortality from 1995 to 2006. The Hypertension Initiative expanded to the Outpatient Quality Improvement Network (O’QUIN) to encompass comparative effectiveness research and other chronic diseases. Lessons learned include: trust enables success, addressing practice priorities powers participation, infrastructure support must be multilateral, and strategic planning identifies opportunities and pitfalls. A collaborative practice network is attainable that produces positive, sustainable, and growing impacts on cardiovascular and other chronic diseases.
Pilates in Heart Failure Patients: A Randomized Controlled Pilot Trial
Authors: Guimarães Guilherme Veiga , Carvalho Vitor Oliveira , Bocchi Edimar Alcides , d’Avila Veridiana Moraes
Published: July 2011

Background: Conventional cardiac rehabilitation program consist of 15 min of warm‐up, 30 min of aerobic exercise and followed by 15 min calisthenics exercise. The Pilates method has been increasingly applied for its therapeutic benefits, however little scientific evidence supports or rebukes its use as a treatment in patients with heart failure (HF). Purpose: Investigate the effects of Pilates on exercise capacity variables in HF. Methods: Sixteen pts with HF, left ventricular ejection fraction 27 ± 14%, NYHA class I–II were randomly assigned to conventional cardiac rehabilitation program (n = 8) or mat Pilates training (n = 8) for 16 weeks of 30 min of aerobic exercise followed by 20 min of the specific program. Results: At 16 weeks, pts in the mat Pilates group and conventional group showed significantly increase on exercise time 11.9 ± 2.5 to 17.8 ± 4 and 11.7 ± 3.9 to 14.2 ± 4 min, respectively. However, only the Pilates group increased significantly the ventilation (from 56 ± 20 to 69 ± 17 L/min, P= 0.02), peak VO2 (from 20.9 ± 6 to 24.8 ± 6 mL/kg/min, P= 0.01), and O2 pulse (from 11.9 ± 2 to 13.8 ± 3 mL/bpm, P= 0.003). The Pilates group showed significantly increase in peak VO2 when compared with conventional group (24.8 ± 6 vs. 18.3 ± 4, P= 0.02). Conclusions: The result suggests that the Pilates method may be a beneficial adjunctive treatment that enhances functional capacity in patients with HF who are already receiving standard medical therapy.
Oral cancer and oral erythroplakia: an update and implication for clinicians
Authors: Villa A , Villa C , Abati S
Published: July 2011

Despite recent advances in therapy and treatment for oral cancer, survival rates are still low. It is generally accepted that oral cancer may arise from potentially premalignant disorders. Oral erythroplakia has been identified as the one with the highest malignant transformation rates. The aim of this review was to provide detailed information on oral cancer and oral erythroplakia. Few data are available on oral erythroplakia and there is an urgent need for randomized controlled trials. Early detection and diagnosis is still the key to survival rates. Dentists and physicians may play an important role in the detection of premalignant lesions and therefore improve patients’ outcome.
A Systematic Review of Vaccinations to Reduce the Shedding of Escherichia coli O157 in the Faeces of Domestic Ruminants
Authors: Snedeker K. G. , Campbell M. , Sargeant J. M.
Published: July 2011

The objective of this study was to conduct a systematic review and meta‐analysis of the published literature to evaluate the efficacy of vaccines in reducing faecal shedding of Escherichia coli O157 in ruminants. A systematic search of eight databases and land‐grant university research reports using an algorithm adapted from a previous systematic review of pre‐harvest interventions against E. coli O157 was conducted to locate all reports of in vivo trials of E. coli O157 vaccines in ruminants published between 1990 and 2010. All located references were screened by two independent reviewers, and data were extracted from all relevant papers, with treatment effect measured in odds ratios. For trials with a faecal prevalence outcome that did not involve mixing of treated and untreated cattle in the same pen, efficacy was explored using random‐effects meta‐analysis. Funnel plots were used to evaluate publication bias, and random‐effects meta‐regression was performed to explore heterogeneity. The search located 20 relevant manuscripts which detailed 24 trials and 46 treatment comparisons; all but one trial involved cattle. There were 9 deliberate challenge trials (19 comparisons), and 15 natural exposure trials (27 comparisons). For Type III protein vaccines, there were 9 natural exposure trials detailing 17 comparisons, and meta‐analysis of 8 comparisons revealed that vaccine treatment resulted in a statistically significant reduction in E. coli O157 faecal prevalence [odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.29, 0.51]. Siderophore receptor and porin protein (SRP) vaccines (three trials/four comparisons) also reduced faecal prevalence (OR = 0.42, 95% CI = 0.20, 0.61); however, none of the bacterin vaccine trials (n = 3, six comparisons) resulted in a statistically significant reduction in prevalence. The results suggest that Type III protein and SRP vaccines significantly reduce faecal shedding in cattle; however, caution should be taken in interpreting the results because of the heterogeneity in the results.
The Effect of Geographic Location, Breed, and Pituitary Dysfunction on Seasonal Adrenocorticotropin and α‐Melanocyte‐Stimulating Hormone Plasma Concentrations in Horses
Authors: McFarlane D. , Paradis M.R. , Zimmel D. , Sykes B. , Brorsen B.W. , Sanchez A. , Vainio K.
Published: July 2011

Background: Plasma α‐melanocyte‐stimulating hormone (α‐MSH) and adrenocorticotropin (ACTH) concentrations in horses vary with season, confounding diagnostic testing for pituitary pars intermedia dysfunction (PPID).

Hypothesis: The goals of this study were to determine whether seasonal variation in plasma α‐MSH and ACTH concentrations in horses is influenced by geographic location, breed, or PPID.

Animals: Healthy light breed horses residing in Florida, Massachusetts, and Finland (n = 12 per group); healthy Morgan horses (n = 13); healthy ponies (n = 9) and horses with PPID (n = 8).

Methods: Monthly plasma α‐MSH and ACTH concentrations were measured by radioimmunoassay. Nonlinear regression analysis was used to estimate the time of peak hormone concentrations. Mean hormone concentrations in fall and nonfall months were compared.

Results: The fall peak plasma α‐MSH concentration occurred earlier in horses residing at more northern locations. Mean seasonal α‐MSH concentrations were similar in all healthy groups at all locations, but in the fall, plasma ACTH concentrations were higher in horses living in more southern locations. Plasma ACTH but not α‐MSH concentrations were higher in Morgan horses compared with light breed horses from the same location. Hormone concentrations of ponies did not differ from those of horses during either season. Concentrations of both hormones were high in the fall compared with the spring in horses with PPID.

Conclusions and Clinical Importance: These findings suggest geographic location of residence and breed may affect the onset, amplitude, or both of the seasonal peak of pars intermedia (PI) hormones and should be considered when performing diagnostic testing for PPID. Horses with PPID maintain seasonal regulation of PI hormone output.
Clinical and Immunomodulating Effects of Ketamine in Horses with Experimental Endotoxemia
Authors: Alcott C.J. , Sponseller B.A. , Wong D.M. , Davis J.L. , Soliman A.M. , Wang C. , Hsu W.
Published: July 2011

Background: Ketamine has immunomodulating effects both in vitro and in vivo during experimental endotoxemia in humans, rodents, and dogs.

Hypothesis: Subanesthetic doses of ketamine will attenuate the clinical and immunologic responses to experimental endotoxemia in horses.

Animals: Nineteen healthy mares of various breeds.

Methods: Experimental study. Horses were randomized into 2 groups: ketamine‐treated horses (KET; n = 9) and saline‐treated horses (SAL; n = 10). Both groups received 30 ng/kg of lipopolysaccharide (LPS,Escherichia coli, O55:B5) 1 hour after the start of a continuous rate infusion (CRI) of racemic ketamine (KET) or physiologic saline (SAL). Clinical and hematological responses were documented and plasma concentrations of tumor necrosis factor‐α (TNF‐α) and thromboxane B2(TXB2) were quantified.

Results: All horses safely completed the study. The KET group exhibited transient excitation during the ketamine loading infusion (P< .05) and 1 hour after discontinuation of administration (P< .05). Neutrophilic leukocytosis was greater in the KET group 8 and 24 hours after administration of LPS (P< .05). Minor perturbations of plasma biochemistry results were considered clinically insignificant. Plasma TNF‐α and TXB2production peaked 1.5 and 1 hours, respectively, after administration of LPS in both groups, but a significant difference between treatment groups was not demonstrated.

Conclusions and Clinical Importance: A subanesthetic ketamine CRI is well tolerated by horses. A significant effect on the clinical or immunologic response to LPS administration, as assessed by clinical observation, hematological parameters, and TNF‐α and TXB2production, was not identified in healthy horses with the subanesthetic dose of racemic ketamine utilized in this study.
Mycoplasma bovisInfections in Cattle
Authors: Maunsell F.P. , Woolums A.R. , Francoz D. , Rosenbusch R.F. , Step D.L. , Wilson D.J. , Janzen E.D.
Published: July 2011

Mycoplasma bovisis a pathogen causing respiratory disease, otitis media, arthritis, mastitis, and a variety of other diseases in cattle worldwide. It is increasingly recognized by the veterinary and livestock communities as having an important impact on the health, welfare, and productivity of dairy and beef cattle.M. bovisdiseases can be difficult to diagnose and control because of inconsistent disease expression and response to treatments and vaccines, and large gaps in our understanding of the epidemiology and pathophysiology of these diseases. There are limited data on which to base evidence‐based decisions for treatment and control, and the literature contains differing clinical biases and opinions. This document is intended for veterinarians dealing with cattle and is focused on the cattle production systems of North America. The goal of the consensus statement panel was to encourage an evidence‐based approach toM. bovisproblems. The scientific literature was critically reviewed, including peer‐reviewed journal articles and reviews obtained by database searches using the terms “Mycoplasma bovis”or “mycoplasma + cattle.” Where other data were lacking, conference proceedings were reviewed as a source of expert opinion.
Age Variation in the Prevalence of DSM‐IV Disorders in Cases of Suicide of Middle‐Aged and Older Persons in Sydney
Authors: Snowdon John , Draper Brian , Wyder Marianne
Published: July 2011

Data concerning 127 persons aged 35 years or above who died by suicide (as determined in consecutive cases by a Sydney coroner) were analyzed. Psychological autopsy (PA) interviews were conducted in 52 cases, and details were compared with the 75 cases where data were available only from coroner’s files (CF). Most characteristics of the two groups were similar, although more CF suicide victims were of Asian background and unable to speak English fluently. Consensus diagnoses were reached following detailed discussion about PA and CF cases. Logistic regression showed no significant difference between age‐groups in the proportion diagnosed with major depression, which contrasts with the results of an earlier U.S. study.
The Geographic Distance of Relocation Search: An Extended Resource‐Based Perspective
Authors: Knoben Joris
Published: July 2011

abstract

On the basis of the extended resource‐based view of firms, access to external resources can be argued to depend on a firm's location. In this article, I test the notion that firms take the availability of these external resources at a given location into account in the distance of their relocation search. The results show that firms take the strength of, and distance to their interorganizational relationships, as well as regional characteristics, into account when determining the distance of their relocation search. They provide empirical validation of the importance of external resources in the resource‐based view of firms. Moreover, they show how a particular type of dynamics, namely, location dynamics, can be used by firms to gain access to resources that can subsequently lead to competitive advantage.
An Improved Anisotropic Tertiary Creep Damage Formulation
Authors: Stewart Calvin M. , Gordon Ali P. , Ma Young Wha , Neu Richard W.
Published: July 2011

Directionally solidified (DS) Ni-base superalloys are commonly used as gas turbine materials to primarily extend the operational lives of components under high load and temperature. The nature of DS superalloy grain structure facilitates an elongated grain orientation, which exhibits enhanced impact strength, high temperature creep and fatigue resistance, and improved corrosion resistance compared with off-axis orientations. Of concern to turbine designers are the effects of cyclic fatigue, thermal gradients, and potential stress concentrations when dealing with orientation-dependent materials. When coupled with a creep environment, accurate prediction of crack initiation and propagation becomes highly dependent on the quality of the constitutive damage model implemented. This paper describes the development of an improved anisotropic tertiary creep damage model implemented in a general-purpose finite element analysis software. The creep damage formulation is a tensorial extension of a variation in the Kachanov–Rabotnov isotropic tertiary creep damage formulation. The net/effective stress arises from the use of the Rabotnov second-rank symmetric damage tensor. The Hill anisotropic behavior analogy is used to model secondary creep and tertiary creep damage behaviors. Using available experimental data for a directionally solidified Ni-base superalloy, the improved formulation is found to accurately model intermediate oriented specimen.
Improving the quality of barrier/seed interface by optimizing physical vapor deposition of Cu Film in hollow cathode magnetron
Authors: Dulkin A. , Ko E. , Wu L. , Karim I. , Leeser K. , Park K. J. , Meng L. , Ruzic D. N.
Published: July 2011

The quality of physical vapor deposition (PVD) grown barrier/seed interface in Cu interconnect metallization was significantly improved by enhancing Cu nucleation on the Ta barrier surface. This was accomplished through filtering of nonenergetic species from the deposition flux, increasing the fraction of Cu ions, improving metal ion flux uniformity, and minimizing gas ion bombardment of the growing film. The self-sputtering ability of Cu was combined with a magnetically confined high-density plasma in the Novellus hollow cathode magnetron (HCM®) PVD source. Spatial profiles of plasma density and temperature, as well as ion flux, metal ion fraction, and ion energy, were measured by planar Langmuir probes, quartz crystal microbalances, and gridded energy analyzers, all located at the wafer level. Multiple criteria, such as seed step coverage and roughness, the seed layer’s resistance to agglomeration, and its stability in the plating bath, have been used to evaluate interface quality. As a result, a new and improved Cu PVD process which demonstrates superior stability during subsequent process steps and ensures successful electrofill performance with a more than 50 % reduction in minimal requirement of field thickness as well as sidewall thickness has been developed.
Streamlined inexpensive integration of a growth facility and scanning tunneling microscope for in-situ characterization
Authors: Xu P. , Qi D. , Barber S. D. , Cook C. T. , Ackerman M. L. , Thibado P. M.
Published: July 2011

The integration of a scanning tunneling microscope chamber with a sample growth facility using non-custom, commercially available parts is described. The facility also features a newly designed magnetic wobble stick to increase the reliability of sample transfer in a cost-effective manner.
S3.2 The role of community based randomised trials in the evaluation of public health interventions
Authors: Donner A
Published: July 2011

In this talk I discuss methodological issues that arise in trials in which intact communities are allocated to each of several intervention groups. The issues discussed include the choice between a randomised and non-randomised design, the need to avoid selection bias when community members are sub-sampled, and the challenges involved in maintaining study power. Ethical issues unique to community intervention trials are also discussed.
S3.3 Use of transmission dynamics models to design and evaluate the impact of large scale HIV/STI prevention intervention: how, why and when?
Authors: Boily M C
Published: July 2011

When HIV or STI prevention programmes (eg, large core group intervention, human papillomavirus vaccination programme) are being scaled up to entire populations, it often becomes difficult to conduct randomised experiments to evaluate their impact. In this talk, I will discuss some of the challenges often present when evaluating large scale interventions and how and why transmission dynamics models, in combination with surveillance data, should be used to address some of these issues and to help estimate the intervention impact more objectively. Mathematical models should also be used at an early stage, not only to choose the most optimal prevention package, but to optimally design and validate evaluation studies in a cost-effective manner.
S3.4 Multi-level strategies to evaluate the impact of HIV prevention programmes in Zimbabwe
Authors: Gregson S
Published: July 2011

Zimbabwe has experienced one of the largest and most rapid declines in HIV prevalence in sub-Saharan Africa. This presentation will describe the range of evidence has been assembled and examined to distinguish the contribution of HIV prevention programmes to this decline from the effects of the natural dynamics of the epidemic, spontaneous responses to high AIDS mortality, and changes in socio-economic context. Some of the practical challenges, advantages and limitations of the different methods of evaluation used—observational studies, mathematical modelling, randomised trials—will be discussed.
S4.1 Challenges in global estimates of syphilis in pregnancy
Authors: Newman L , Hawkes S , Kamb M , Toskin I , Say L , Broutet N
Published: July 2011

Background

Estimates of the current number of pregnant women infected with syphilis (maternal syphilis) are necessary for the global Elimination of Congenital Syphilis initiative such that advocacy, program implementation, and monitoring are based on a clear understanding of the current situation. In addition to understanding morbidity in pregnant women, an accurate estimate of maternal syphilis is also the cornerstone of calculations of the burden of adverse outcomes associated with syphilis in pregnancy.

Methods

A MEDLINE search from January 2003 to September 2010 was conducted to identify studies of syphilis prevalence in women attending antenatal care with the following inclusion criteria: sample size of at least 100, use of both reaginic and non-reaginic tests, English language, and no apparent selection bias. Methods are similar to those used by Schmidet alin 2007 to estimate maternal syphilis, except that current estimates include Europe and North America, and will be compared with syphilis seropositivity data reported by countries through the WHO HIV Universal Access reporting system for 2008 through 2010 (reported data may or may not use both reaginic and non-reaginic tests). Global and regional estimates will be based on country data where available, and where not available, a regional pregnancy-weighted mean based on live births (per United Nations Population Division) and known country seropositivity will be used. Country and regional estimates will be validated by WHO regional advisors to assess if estimates are reasonable.

Results

Studies on approximately 35 of 193 countries (18%) met the inclusion criteria for the MEDLINE search, and 96 countries (50%) reported seropositivity in either 2008 or 2009; additional reported data for 2010 will be available in May 2011, at which time estimates will be completed.

Conclusions

Data on maternal syphilis are available in recent published literature for only a small proportion of countries. Therefore, global and regional estimates of maternal syphilis must rely on alternative data sources such as the WHO HIV Universal Access reporting system. Increased efforts are required globally to highlight the importance of having sufficient high-quality data to guide implementation of congenital syphilis elimination efforts.
S4.3 Implementation of rapid tests for prenatal syphilis screening: overcoming health system constraints
Authors: Garcia P J , Peeling R , Mabey D , Holmes K K ,   The CISNE team (Spanish word for SWAN)
Published: July 2011

Background

Congenital syphilis and syphilis in pregnancy in Peru persist as important public health issues, and improvement of screening/treatment for pregnant women remains challenging. rapid syphilis testing (RST) allows simple and immediate diagnosis and treatment at a single clinic visit and could increase screening and treatment coverage and thereby reduce the incidence of stillbirth and congenital syphilis and generate in the long term a sustainable cost effective intervention.

Methods

We tested the feasibility, performance, impact and cost-effectiveness of implementing RST in an underserved urban area at a biggest maternity hospital in Peru and a network of 16 peripheral health centres offering prenatal care in a periurban poor area in Callao-Ventanilla, Peru. RST (integrated with HIV rapid test: the “two for one”) were offered at the first prenatal visit (ANC), at delivery and within miscarriage/abortion services.

Results

Data from the baseline pre-implementation evaluation revealed limited coverage of screening and treatment services for maternal syphilis and a complex and inefficient system for ANC. RST was started in January 2010. Overall success of implementation was measured by rates of maternal syphilis screening and treatment coverage, partner treatment, and acceptability of RST among providers and patients. Complementary evaluations comparing cost-effectiveness of RST against the Rapid Plasma Reagin, and a performance analysis of RST against the “multiple gold test” [Rapid Plasma Reagin +Treponema pallidumparticle agglutination assay or fluorescent treponemal antibody absorption] were also simultaneously performed. Attention was paid to the successful development of a system of internal and external quality control for testing and test supplies and the process of dissemination and transfer activities to the Ministry of Health of Peru, through the involvement of both the National Program of STIs and HIV and the Reproductive Health Program. National guidelines have been modified, and recommend the use of both tests, RST and rapid HIV testing in the screening of pregnant women.

Conclusions

RST implementation was feasible, successful, acceptable and cost effective. Its introduction catalysed improvements in the quality of care, and by the end of the project it has been introduced in the country as a national policy.
S4.4 Progress in development of dual rapid syphilis test technology
Authors: Cox D L
Published: July 2011

Background

Traditionally, most diagnoses of syphilis relies on serology and required testing for patient antibodies against cardiolipin (non-treponemal tests) as well as against treponemal antigens (treponemal tests). These serological tests must be performed in clinical laboratories, require considerable scientific resources and trained technicians to perform them, and test results often are not reported for several days. As a result, control in resource-poor countries has been problematic. Rapid tests provide a platform whereby patient antibodies can be quickly analysed (5–30 min) by their binding to immobilised antigens on a nitrocellulose membrane. Another advantage is that patient sera, blood, or plasma can be tested, thus requiring fewer resources and technician time to perform. One of the first rapid tests developed was the Abbot Determine (treponemal test results only) which has served as a useful rapid screening tool in some settings. Other treponemal only rapid tests include the Standard Diagnostics BioLine and the Fujirebio Espline. These rapid tests have a sensivitivity ranging from 92% to 100% and specificity ranging from 93.4 to 98.9% when compared to the TP-PA. The Eurostrip (Euromedi Equipment LTD, W. Harrow, UK), another treponemal only rapid test, was recently evaluated at CDC for a potential field study in Kenya. With 94 archived serum samples, the Eurostrip had a sensitivity of 98.6% and a specificity of 100% when compared to the TP-PA.

Methods and results

A recent breakthrough in technology allows for modified cardiolipin to be attached to membranes, and the first generation of dual rapid tests were developed in collaboration with CDC: the ChemBio DPP Screen and Confirm (ChemBio Diagnostic Systems, Medford, New York, USA) and the Span Spirolipin (Span Diagnostics Inc., Surat, India). In a study with 1601 archived serum samples, the non-treponemal component of the ChemBio DPP had a sensitivity of 97.3% and a specificity of 98.6% when compared to the RPR; the treponemal component had a sensitivity of 97% and a specificity of 95.5% when compared to the TP-PA. In a similar study with 376 archived serum samples, the non-treponemal component of the Span Spirolipin had a sensitivity of 96.5% and a specificity of 97.7% when compared to the RPR and the treponemal component had a sensitivity of 97.3% and a specificity of 99.1% when compared to the TP-PA. These evaluations demonstrate that these dual rapid tests are as sensitive and as specific as traditional RPR and TP-PA tests.

Conclusions

The emergence of dual rapid tests offers resource-poor countries the opportunity for improved point-of-care diagnostic capacity. Span has recently announced that they can market the Spirolipin dual test for <1 USD per cassette, which would make these tests affordable in many settings. Future developments in rapid testing include the addition of antigen(s) to also test for HIV infection, offering even more diagnostic options to control these diseases, especially among pregnant women.
S5.2 Action heroes or casual observers: vaginal microflora and STI/HIV risk
Authors: Hillier S
Published: July 2011

Some components of the microbial flora of the vagina, most notably lactobacilli, have been linked with decreased rates of bacterial and viral STIs, including HIV, mucopurulent cervicitis and pelvic inflammatory disease. However, the same sexual activity which adversely impacts vaginal colonisation by lactobacilli increases risk of STIs. Therefore, the apparent protective benefits of lactobacilli could reflect co-epidemiology rather than an independent biological benefit of these microorganisms.This presentation will present a summary of the epidemiological data linking vaginal microflora to HIV/STI risk and evidence suggesting that lactobacilli play a causal role in reducing risk of STI/HIV in women.
S5.4 Identifying knowledge gaps in the evidence base for repeat screening of women with chlamydia and gonorrhoea: challenges to public health action
Authors: Bernstein K
Published: July 2011

There is strong evidence that repeat chlamydia and gonorrhoea infections among women are associated with adverse reproductive health outcomes.

However, effective interventions to reduce re-infection are not well-articulated or well-coordinated in STD control programs. Gaps in knowledge about the immunology of chlamydial and gonococcal infections coupled with a poor understanding of adolescent and young adult sexual networks limit progress towards developing effective interventions.

This presentation will review the current epidemiology of repeat chlamydia and gonorrhoea among women and highlight the operational challenges to implementing programmatic responses to reducing the burden and impact of repeat infection, including increasing rescreening rates, use of partner delivered therapy, and other approaches to interrupt ongoing transmission in high prevalence sexual networks.
S7.1 Achieving high coverage of HIV prevention services for MARPs: Avahan's experience in six states in India
Authors: Kumta S
Published: July 2011

In 2003, the Bill and Melinda Gates foundation initiated “Avahan” a large scale HIV prevention program in India. The goal was to halt the HIV epidemic in India by rapidly building a scaled HIV prevention program for core and bridge population groups across 4 Southern and 2 Northeastern states in India representing approximately 80% of India's HIV burden in 2002. Avahan offered a standardised package of known and proven prevention interventions to high-risk groups and bridge populations in the geographic areas most affected by the epidemic. The program reached 220 000 female sex workers; 80 000 High risk MSM; 18 000 Injecting drug users and 5 million men at risk. By December 2008, Avahan had achieved significant scale and coverage with over 75% of total denominator including FSW and high risk MSM contacted monthly through outreach. The presentation will include the challenges at the start of the program, Avahan approaches to rapid scale up while leveraging data to ensure focus on highest at risk through provision of a standardised package of services (known as the Common Minimum Program).
S7.2 Measurement and community mobilisation do not have to be mutually exclusive: preliminary analysis from a scaled programme
Authors: Wheeler T
Published: July 2011

Community mobilisation approaches within the HIV/AIDS landscape have rarely operated at a significant scale, or been designed with the conceptual and technical clarity necessary to be measured effectively. Measurement of community mobilisation by necessity has been undertaken through innovative qualitative approaches but these have often lacked the rigour or complementary qualitative methods to provide adequate analysis on the association with outcomes or the path to generating HIV/AIDS outcomes. Avahan may provide new insights into community mobilisation and structural interventions as an effective and replicable approach within comprehensive HIV prevention programming. The experience of retrofitting measurement into a “living” programme and developing measurement indicators and tools to work at scale provide practical examples of what can be done. The Avahan logic model, proposed measurement approach and some preliminary analysis of risk reduction and sustainability outcomes as a result of community mobilisation and structural interventions will be presented.
S1.3 Measurement of adherence: where are we?
Authors: Van der Straten A
Published: July 2011

There is presently no validated objective method available to measure participants' sexual behaviour or adherence to study product use in HIV prevention trials. Because of this challenge there has been an indeterminate amount of product non-adherence that has precluded the accurate measurement of the safety and efficacy of novel biomedical interventions. Measurement has historically relied on self-report, which suffers from several biases, including recall and social desirability. To address these, researchers have use alternative interview modes (ACASI) and technologies (cell phones/SMS) with varying success. Pros and cons of other innovative approaches to measure adherence will be discussed, including use of indirect objective measures of adherence (eg, events monitoring systems, mucin tests of gel applicators), real time electronic measures, biomarkers and Directly Monitored Adherence Methods. Each of these approaches has strengths and limitations, thereby precluding any of them from serving as a universal “gold standard”. Discussion will include what can and should be measured “objectively” as well as lessons learnt for future biomedical prevention trials.
S8.1 Lessons learnt from global HIV drug resistance initiative: implications for MDR-GC
Authors: Sutherland D
Published: July 2011

The WHO, in collaboration with the Bill and Melinda Gates Foundation and the International AIDS Society developed the Global HIV Drug Resistance Network. It is comprised of a network of countries and accredited laboratories. The Network serves as an advisory and evaluation function to the WHO HIV drug resistance team and countries implementing the strategy. Surveillance of HIV drug resistance is critical because it helps to detect the circulation of resistance strains and directs measures to preserve programme effectiveness.

This presentation will explore how lessons learnt from the HIV drug resistance initiative could be applied to slow the spread of MDR-GC.
S9.2 Monitoring and evaluation: linking programming and research
Authors: Vassall A
Published: July 2011

Researchers are becoming increasingly interested in the evaluation of STI/HIV interventions that take place in “real world” programmatic or health systems settings. Likewise, programme and health service managers are facing ever growing demands to demonstrate results and achieve “value for money”. Monitoring and evaluation (M&E) systems are fundamental to both efforts. However, research and programme efforts are often not closely linked, with data being collected and analysed independently.

This presentation will examine M&E from a researchers' perspective. It will outline how a programme science perspective can contribute to the development of robust and useful M&E systems and processes. We will present two case studies. The first, the Integra project, evaluates the integration of HIV and SRH services in Kenya and Swaziland. It illustrates how research complemented routine M&E systems in a “real world” setting. This case demonstrates the benefits to programme managers of combining M&E data with economic research to enhance service performance. At the same time Integra researchers were able to use M&E data to examine the impact of “real world” issues like drug stock-outs on their research results. The second case study, the CHARME project, is an evaluation of the Avahan HIV prevention programme in India. This case illustrates the value of linking monitoring systems with research efforts to establish plausible evidence of the relationship between cost, programme activities and intensity and impact of an HIV prevention programme; where no control areas or “stepped wedge” evaluation design was feasible, due to rapid scale-up.

Finally, the presentation will identify a number of over-arching lessons learnt from these cases, and other experiences. It will highlight the importance of investing in a wide range of monitoring and evaluation activities, that go beyond Management Information Systems and qualitative peer evaluation. It will explore ways of enhancing and linking research and programme efforts, so that M&E can relate STI/HIV inputs, outputs and outcomes in a robust and logical way; but, at the same time, remains feasible and “value for money” in large scale “real world” settings.