bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of Law and Ethics in Matters of Advertisers' Responsibility for Protecting Consumers
Authors: PRESTON IVAN L.
Published: March 2010

There are basic dilemmas involving the interaction of advertising regulation and advertising ethics, and their relation to social responsibility in the field. Analysis contributes to understanding them, and hopefully to resolution as well.
Women's perceptions relating to the introduction of mandatory iodine fortification in Australia
Authors: YEATMAN Heather , PLAYER Chantell , CHARLTON Karen
Published: March 2010

Aim:  In Australia, the mandatory fortification of salt used in bread with iodine has recently been approved by the regulatory authorities (Food Standards Australia New Zealand). Apart from thiamine fortification of bread that has been in place since 1991, no other mandatory fortification programs exist in the country. The aim of the present study was to explore women's understanding of mandatory fortification as a public health strategy and their opinions regarding its appropriateness for addressing the re‐emergence of iodine deficiency.

Methods:  Four focus group discussions with 20 women of child‐bearing age, recruited from Wollongong in New South Wales.

Results:  Women had little knowledge about the role of iodine in the diet and were unaware that iodine deficiency was a public health issue in Australia. Mandatory fortification was viewed with concern, especially regarding the possible risk of toxicity. Clear labelling of fortified foods, in conjunction with education initiatives to accompany the pending iodine fortification program, were considered by the research participants to be essential in order to address these concerns.

Conclusion:  Women in the present study expect an authority, either a government body or health professionals, to take responsibility in making proactive decisions for the health of the population. When accompanied by transparent processes that include widespread consultation with consumers and clear explanations for the process, mandatory fortification is considered acceptable as an appropriate and effective strategy for ameliorating iodine deficiency.
Which Australian food composition database should I use?
Authors: SOBOLEWSKI Renee , CUNNINGHAM Judy , MACKERRAS Dorothy
Published: March 2010

Aim:  This paper describes the differences between the NUTTAB and AUSNUT food composition databases now available in Australia.

Method:  The NUTTAB and AUSNUT food composition databases are described in detail by officers of Food Standards Australia New Zealand directly involved in the database management and development. The positions of Food Standards Australia New Zealand in terms of revisions and policy directions are given from an authoritative perspective.

Results:  Food Standards Australia New Zealand develops two different sets of food composition databases, NUTTAB and AUSNUT. NUTTAB is a reference database that contains primarily analysed data for Australian foods. AUSNUT is a survey database that contains only data that are directly relevant to the particular national nutrition survey for which it was developed. These databases are available free of change from the Food Standards Australia New Zealand website.

Conclusions:  Food Standards Australia New Zealand develops two distinct series of food composition databases. Users will need to be aware of the similarities and differences of each database type to be able to determine which is the most suitable for their needs.
Food advertisements containing ‘scientific’ and ‘lay person’ keywords: Responses from a sample of female Australian consumers
Authors: MCMAHON Anne‐Therese , TAPSELL Linda , WILLIAMS Peter , MOTION Judy , JONES Sandra C.
Published: March 2010

Aim:  To describe female consumer responses to food advertisements containing nutrition messages differentiated by use of ‘scientific’ and ‘lay person’ keywords.

Method:  ‘Lay person’ and ‘scientific’ keywords were identified in advertisements from an audit of Australia's 30 top circulation magazines by people with or without formal scientific training in nutrition. Eight sample print advertisements were selected for consideration in focus group interviews. Four semistructured qualitative focus group interviews were conducted (women 25–63 years, n = 25 participants in total). Each group discussed four advertisements (two with ‘lay person’ and two with ‘scientific’ nutrition keywords). Thematic content analysis, including constant comparison and consensus, was driven by identifying types of responses and attributed meanings of keywords.

Results:  Participants' responses to the sample advertisements ranged from giving an immediate judgement, attributing meaning to keywords, responding to the keyword's novelty, describing the process of information analysis and addressing tangential issues such as photographic cues. The diversity in response occurred whether the advertisement contained ‘scientific’ or ‘lay person’ keywords and reflected the influence of multiple discourses on perceptions of the credibility and persuasiveness of nutrition messages

Conclusions:  Consumers' responses to keywords in advertisements are complex. Communications research that tests the message in its total context is needed to ensure the meaning of nutrition messages are being conveyed as is intended.
Diet quality and anthropometry between different sailboarding styles
Authors: DOUMTSIOS Ioannis , GRAMMATIKOPOULOU Maria G. , TSIGGA Maria
Published: March 2010

Aim:  To identify diet quality and basic anthropometric characteristics of sailboarders.

Methods:  The study was conducted in 91 sailboarders, who were divided in two groups according to muscle recruitment during sailing; those performing wave or freestyle surfing formed the WF group (n = 46) and those performing slalom or formula the SF group (n = 45), as the first includes more lower‐body muscle recruitment. Diet and anthropometry were evaluated during training days and compared between the two study groups.

Results:  The WFs demonstrated lower % body fat (21%), circumferences, skinfolds, body mass index (23.9 kg/m2) and fat mass index (5.1 kg/m2) compared with the SFs (body fat 25.2%, body mass index 26.1 kg/m2 and fat mass index 6.6 kg/m2). Dietary intake was similar and both groups presented a negative energy balance, high cholesterol intake and adequacy in the intake of most micronutrients except for vitamin E of the WF group. The windsurfers achieved a low healthy eating index (54.3 and 58.1 for WF and SF respectively), indicative of a diet in need of improvement and reported the post‐training consumption of beer and fast food.

Conclusion:  Overall findings suggest the need for dietary counselling in windsurfers, as glycogen depletion is crucial in sailboarding, where one athlete consists of the total boat crew thus, glycogen depletion leading to insufficient energy for technical movements while sailing, has direct effect on the result of the race.
Function and Structure of Resistance Vessels in Black and White People
Authors: Taherzadeh Zhila , Brewster Lizzy M. , Van Montfrans Gert A. , VanBavel Ed
Published: March 2010

J Clin Hypertens (Greenwich). 2010;12:431–438. ©2010 Wiley Periodicals, Inc.

The risk of development of hypertension is greater in black people compared to white people through mechanisms that are poorly understood. Several biological and environmental factors have been proposed. Based on the role of an increased peripheral resistance in the pathogenesis of hypertension, the authors focus in this systematic review on ethnic differences in function and mechanical properties of resistance arteries in normotensive participants. PubMed was systematically searched for papers on ethnic differences in vascular function and structure. A total of 620 papers were retrieved, of which 31 papers were included in the analysis. The available data indicate that compared to normotensive whites, normotensive black people have enhanced vascular reactivity to sympathetic stimulation, attenuated responses to vasodilators, and a relatively narrow vascular lumen diameter. Of these mechanisms, the reduced vasodilation and reduced nitric oxide bioavailability in the vascular wall seem to form the most important distinction between resistance vessel properties of black and white participants.
S‐Allyl‐Mercapto‐Captopril: A Novel Compound in the Treatment of Cohen‐Rosenthal Diabetic Hypertensive Rats
Authors: Younis Firas , Mirelman David , Rabinkov Aharon , Rosenthal Talma
Published: March 2010

J Clin Hypertens (Greenwich). 2010;12:451–455. ©2010 Wiley Periodicals, Inc.

S‐allyl‐mercapto‐captopril (CPSSA) is a conjugate of captopril with allicin, an active principle in garlic with multiple beneficial actions on metabolic syndrome abnormalities, including weight preservation, observed by the authors in fructose‐induced hypertensive hyperinsulinemic rats and in Koletsky rats. The aim of the study was to examine blood pressure (BP) and glucose levels in the Cohen‐Rosenthal Diabetic Hypertensive (CRDH) model as well as to follow their weight preservation. CRDH rats (n=14) were fed the sugar‐rich copper‐free diet essential for the development of diabetes mellitus. Two months later BP and blood glucose levels were measured. CPSSA was diluted in drinking water and administered at a final dose of 53.5 mg/kg/d (n=8). Control rats (n=6) received no drug (vehicle group). In contrast to control group, CPSSA prevented progressive weight gain, without a detectable effect on food and water intake. CPSSA was effective in attenuating systolic and diastolic BP (P<0.01) as well as significantly reducing glucose levels (P<0.01). Control rats continued to gain weight, whereas the groups fed CPSSA did not. CPSSA was shown to have additional beneficial effects on improving BP and glucose level, as well as preserving weight gain. The authors conclude that the combined molecule CPSSA integrates the antihypertensive feature of both allicin and captopril, making it a potential antidiabetic and cardiovascular protective agent.
Controlling biofilm formation, prophage excision and cell death by rewiring global regulator H‐NS of Escherichia coli
Authors: Hong Seok Hoon , Wang Xiaoxue , Wood Thomas K.
Published: March 2010

The global regulator H‐NS of Escherichia coli controls genes related to stress response, biofilm formation and virulence by recognizing curved DNA and by silencing acquired genes. Here, we rewired H‐NS to control biofilm formation using protein engineering; H‐NS variant K57N was obtained that reduces biofilm formation 10‐fold compared with wild‐type H‐NS (wild‐type H‐NS increases biofilm formation whereas H‐NS K57N reduces it). Whole‐transcriptome analysis revealed that H‐NS K57N represses biofilm formation through its interaction with the nucleoid‐associated proteins Cnu and StpA and in the absence of these proteins, H‐NS K57N was unable to reduce biofilm formation. Significantly, H‐NS K57N enhanced the excision of defective prophage Rac while wild‐type H‐NS represses excision, and H‐NS controlled only Rac excision among the nine resident E. coli K‐12 prophages. Rac prophage excision not only led to the change in biofilm formation but also resulted in cell lysis through the expression of toxin HokD. Hence, the H‐NS regulatory system may be evolved through a single‐amino‐acid change in its N‐terminal oligomerization domain to control biofilm formation, prophage excision and apoptosis.
Evaluation of the legal risk of a ‘missed’ cancer in two breastscreen services
Authors: Osborne J , Lee W
Published: March 2010

Variation in opinions of medical experts is a problem for both the legal and medical profession. This is particularly relevant in breast imaging. BreastScreen Queensland and New South Wales have developed a review protocol to assess ‘reasonableness’ of radiological opinions. It is hoped that the protocol will be acceptable to the courts and will result in a fair outcome for all parties involved in a medico‐legal dispute.
How I do it: Lymphangiography
Authors: Plotnik AN , Foley PT , Koukounaras J , Lyon SM
Published: March 2010

Lymphangiography, despite advances in cross‐sectional imaging, remains a useful tool in the diagnosis and therapeutic intervention of lymphatic vessel damage, such as high output chylothorax. This article describes our technique for this procedure.
Evaluation of megavoltage CT imaging protocols in patients with lung cancer
Authors: Smith S , Yartsev S , Van Dyk J
Published: March 2010

Currently, megavoltage CT studies in most centres with tomotherapy units are performed prior to every treatment for patient set‐up verification and position correction. However, daily imaging adds to the total treatment time, which may cause patient discomfort as well as results in increased imaging dose. In this study, four alternative megavoltage CT imaging protocols (images obtained: during the first five fractions, once per week, alternating fractions and daily on alternative weeks) were evaluated retrospectively using the daily position correction data for 42 patients with lung cancer. The additional uncertainty introduced by using a specific protocol with respect to the daily imaging, or residual uncertainty, was analysed on a patient and population bases. The impact of less frequent imaging schedules on treatment margin calculation was also analysed. Systematic deviations were reduced with increased imaging frequency, while random deviations were largely unaffected. Mean population systematic errors were small for all protocols evaluated. In the protocol showing the greatest error, the treatment margins necessary to accommodate residual errors were 1.2, 1.3 and 1.7 mm larger in the left–right, superior–inferior and anterior–posterior directions, respectively, compared with the margins calculated using the daily imaging data. The increased uncertainty because of the use of less frequent imaging protocols may be acceptable when compared with other sources of uncertainty in lung cancer cases, such as target volume delineation and motion because of respiration. Further work needs to be carried out to establish the impact of increased residual errors on dose distribution.
Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer
Authors: Sundaresan P , Yeghiaian‐Alvandi R , Gebski V
Published: March 2010

Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks (‘early death’) may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of ‘early death’. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10‐year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with ‘early death’. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of ‘early death’. Twenty‐three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for ‘early death’. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.
Innovative program for palliative radiotherapy in Australia
Authors: Holt TR , Yau VKY
Published: March 2010

Radiotherapy plays a significant role in the palliation of symptoms in patients with cancer. It can improve symptoms from bone metastases, spinal cord compression, superior vena cava obstruction and cerebral metastases. Long waiting lists and inconvenient access prolong suffering and may even discourage patients from utilising this service. With this in mind, a Rapid Response Palliative Radiotherapy Clinic was established at the Mater Centre – Radiation Oncology Services, Princess Alexandra Hospital in Brisbane. The study evaluates whether the clinic achieves its aim of providing timely and efficient palliative radiotherapy for oncology patients. Data were collected in the first 6 months of the clinic's operation and compared with data from palliative patients seen in other clinics at the same centre over the same period. Patients seen in the Rapid Response Clinic were more likely to have been treated within 24 h of being assessed, and were more likely to have received a single fraction treatment. The clinic fulfils the role of offering a timely and convenient radiation service for palliative patients and acts as a reference for other palliative radiotherapy services in Australia.
Implementation of an image‐guided radiation therapy program: Lessons learnt and future challenges
Authors: Bell LJ , Oliver L , Vial P , Eade TN , Rinks M , Hammond E , Morgan GW , Back M , Wiltshire KL
Published: March 2010

The aim of this paper is to detail the experience obtained in implementing an image‐guided radiation therapy program at the Northern Sydney Cancer Centre. This required retrofitting a Varian Clinac 21EX with an on‐board imager. The commissioning and quality assurance procedures, organisation of a multidisciplinary image guided radiation therapy group, and the development of clinical protocols for orthogonal kV and cone beam computed tomography implementation are described. Reassessment of the image‐guided radiation therapy program has continued as new equipment and software versions were made available in the department.
Central venous catheter tip malposition
Authors: Patel RY , Friedman A , Shams JN , Silberzweig JE
Published: March 2010

Central venous catheters are commonly utilised to gain vascular access for varied clinical indications. Successful central venous catheter placement requires not only technical expertise, but also awareness of the potential complications. This article reviews the major procedural and post‐procedural complications resulting from central venous catheter tip malposition.
A case of emphysematous pyelonephritis in a patient with rheumatoid arthritis taking corticosteroid and low‐dose methotrexate
Authors: WATANABE Hiroshi , SUZUKI Ryoma , ASANO Tomoyuki , SHIO Kiori , IWADATE Haruyo , KOBAYASHI Hiroko , MATSUOKA Toshimitsu , AIKAWA Ken , OHIRA Hiromasa
Published: March 2010

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is characterized by chronic synovial inflammation. Patients with RA have increased risk of infection; this is related to RA itself or the adverse effects of medication. In this report, we describe a case of emphysematous pyelonephritis in a patient with RA associated with AA amyloidosis and steroid‐induced diabetes mellitus who was taking corticosteroid and low‐dose methotrexate.
The Medici syndrome: a medico‐historical puzzle
Authors: WEISZ George M. , MATUCCI‐CERINIC Marco , ALBURY William R. , LIPPI Donatella
Published: March 2010

The historical significance of the Medici family of Florence is widely recognised, but the diseases which afflicted leading members of this family have only been scientifically studied in recent decades. Paleopathological findings on exhumed skeletons, supplemented by medical descriptions in historical documents, have permitted a retrospective diagnosis of a triple pathological syndrome in the senior branch of the Medici family. Peripheral joint and spinal conditions, with the presence of skin disease, are identified in several generations of the family in the 15th century and are presented as the ‘Medici syndrome’. Radiological findings are compared with macro‐ and microscopical descriptions in the diagnosis of the peripheral joint disease and spinal ankylosis/stenosis within the syndrome.
How to deal with Behcet’s disease in daily practice
Authors: DAVATCHI Fereydoun , SHAHRAM Farhad , CHAMS‐DAVATCHI Cheyda , SHAMS Hormoz , NADJI Abdolhadi , AKHLAGHI Massoomeh , FAEZI Tahereh , SADEGHI ABDOLLAHI Bahar
Published: March 2010

Introduction:  Behcet’s Disease (BD) is classified as a vasculitis, and progresses via attacks and remissions. BD is mainly seen around the Silk Road. The picture varies in different reports. For clinical descriptions, the data from the international cohort of patients (27 countries), will be used.

Clinical manifestations:  Mucous membrane manifestations were oral aphthosis seen in 98.1%, and genital aphthosis in 76.9% of patients. Skin manifestations were seen in 71.9% (pseudofolliculitis in 53.6% and erythema nodosum in 33.6%). Ocular manifestations were seen in 53.7% (anterior uveitis 38.8%, posterior uveitis 36.9%, retinal vasculitis 23.5%). Joint manifestations were seen in 50.5% (arthralgia, monoarthritis, oligo/polyarthritis, ankylosing spondylitis). Neurological manifestations were seen in 15.5% of patients (central 11.5%, peripheral 4.4%). Gastrointestinal manifestations were seen in 6.3% of patients. Vascular involvement was seen in 18.2% of patients and arterial involvement in 3% (thrombosis, aneurysm, pulse weakness). Deep vein thrombosis was seen in 8%, large vein thrombosis in 6.5%, and superficial phlebitis in 5.8%. Orchitis and epididymitis were seen in 7.2%. Pathergy test was positive in 49.3% and HLA‐B51 in 49.1% of patients.

Diagnosis:  Diagnosis is based on clinical manifestations. The International Criteria for Behcet’s Disease (ICBD) may be helpful.

Treatment:  The first line treatment is colchicine (1 mg daily) for mucocutaneous manifestations, non‐steroidal anti‐inflammatory drugs for joint manifestations, anticoagulation for vascular thrombosis, and cytotoxic drugs for ocular and brain manifestations. If incomplete response or resistance occurs, therapeutic escalation is worthwhile.

Conclusion:  Behcet’s disease is a systemic disease characterized by mucocutaneous, ocular, vascular and neurologic manifestations, progressing by attacks and remissions.
Reduction of liver stiffness by interferon treatment in the patients with chronic hepatitis C
Authors: Arima Yuko , Kawabe Naoto , Hashimoto Senju , Harata Masao , Nitta Yoshifumi , Murao Michihito , Nakano Takuji , Shimazaki Hiroaki , Kobayashi Kyoko , Ichino Naohiro , Osakabe Keisuke , Nishikawa Toru , Okumura Akihiko , Ishikawa Tetsuya , Yoshioka Kentaro
Published: March 2010

Aim:  To assess the regression of liver fibrosis after interferon (IFN) treatment in patients with chronic hepatitis C, liver stiffness (LS) was measured repeatedly and the factors associated with reduction of LS were assessed.

Methods:  LS was measured by transient elastography before treatment, at end of treatment (EOT), and 1 year and 2 years after EOT in 145 patients with chronic hepatitis C treated by IFN with or without ribavirin.

Results:  In the patients with sustained virological response (SVR) (n = 93) and relapsers (n = 28), LS significantly decreased at EOT (median, 5.4 [interquartile range, 4.0–8.6] kilopascals [kPa], P < 0.0001 and 6.8 [4.5–8.9] kPa, P = 0.0023) and 1 year after EOT (5.3 [4.2–7.0] kPa, P < 0.0001 and 6.8 [4.5–9.3] kPa, P = 0.0204) compared with baseline (8.0 [5.0–11.9] kPa and 10.6 [7.0–16.6] kPa). In SVR patients, LS significantly decreased 2 years after EOT (5.3 [4.1–6.3] kPa) compared with baseline (P < 0.0001) and LS at EOT (P = 0.0034). Two points or greater reduction of deduced stage at last LS measurement was observed in 78% of SVR patients, 59% of relapsers and 15% of patients with non‐virological response whose pretreatment deduced stages were F3–F4. Fibrosis stage, hyaluronic acid levels, duration of treatment, response to treatment and alanine aminotransferase levels were associated with a 2‐point or greater decrease of deduced fibrosis stage.

Conclusion:  IFN treatment reduced LS in SVR patients and relapsers. Significant reduction of LS is associated with milder fibrosis stage, lower hyaluronic acid levels, longer IFN treatment, virological response of SVR or relapse and higher alanine aminotransferase levels.
Chemokine CCL3 facilitates the migration of hepatoma cells by changing the concentration intracellular Ca2+
Authors: Yuan Yufeng , Liu Jun , Liu Zhisu , He Yueming , Zhang Zhonglin , Jiang Congqing , Qian Qun
Published: March 2010

Aim:  Recurrence and metastasis are the major factors associated with the poor prognosis of hepatocellular carcinoma (HCC). It was confirmed that multiple chemokines and their receptors are related to the progression and metastasis of HCC. The aim of this research was to conduct an investigation into whether macrophage inflammatory protein‐1α/CCL3, and its receptor CCR1 play a role in HCC invasion and metastasis.

Methods:  We used reverse transcription polymerase chain reaction, immunocytochemistry and flow cytometry to detect CCR1 mRNA and protein expression in the four hepatoma cell lines HepG2, Hep3B, HLE and HLF; and we conducted a microscope cell migration experiment to observe the pseudopodia formation and mobility of the hepatoma cells. The concentration of intracellular calcium was measured by fluorescence microscopy.

Results:  CCR1 mRNA and protein were positively expressed in the four hepatoma cell lines HepG2, Hep3B, HLE and HLF. Following CCL3 stimulation, obvious pseudopodia formation of hepatoma cells was observed using a fluorescence microscope. The cell migration experiment showed that after incubation with CCL3, the number of Hep3B cells which passed through the polycarbonate microporous filter membranes increased to an obvious extent. After CCL3 incubation, the intracellular Ca2+ level of the Hep3B cells increased to an obvious extent.

Conclusion:  Chemokine CCL3 facilitates the migration of hepatoma by changing the concentration intracellular Ca2+. The CCL3–CCR1 axis may play an important role in HCC invasion and metastasis. It may also be a potential target for HCC therapy or for prevention of the recurrence and metastasis of HCC.
On the Benefits of Risk Pooling in Inventory Management
Authors: Berman Oded , Krass Dmitry , Mahdi Tajbakhsh M.
Published: March 2010

We analyze the benefits of inventory pooling in a multi‐location newsvendor framework. Using a number of common demand distributions, as well as the distribution‐free approximation, we compare the centralized (pooled) system with the decentralized (non‐pooled) system. We investigate the sensitivity of the absolute and relative reduction in costs to the variability of demand and to the number of locations (facilities) being pooled. We show that for the distributions considered, the absolute benefit of risk pooling increases with variability, and the relative benefit stays fairly constant, as long as the coefficient of variation of demand stays in the low range. However, under high‐variability conditions, both measures decrease to zero as the demand variability is increased. We show, through analytical results and computational experiments, that these effects are due to the different operating regimes exhibited by the system under different levels of variability: as the variability is increased, the system switches from the normal operation to the effective and then complete shutdown regimes; the decrease in the benefits of risk pooling is associated with the two latter stages. The centralization allows the system to remain in the normal operation regime under higher levels of variability compared to the decentralized system.
Proactive Planning of the Timing of a Partial Switch of a Prescription to Over‐the‐Counter Drug
Authors: Fruchter Gila E. , Mantrala Murali K.
Published: March 2010

This paper focuses on the proactive planning of a partial switch of a prescription (Rx) drug brand to over‐the‐counter (OTC) status within the former's patent‐protected life. The planning issues are whether and when to make this switch from the “single‐status” Rx drug phase to the “dual‐status” Rx+OTC phase with or without the grant of a 3‐year market exclusivity period for the OTC drug by the US Food and Drug Administration. We formulate an optimal control problem that leads to a two‐phase optimization problem with finite‐time horizon involving switching time‐dependent switching cost and terminal value. Applying a variational approach, we establish the conditions under which it can be optimal to make the partial switch. Counter to conventional thinking, the grant of market exclusivity is neither necessary nor sufficient for a partial switch before the Rx drug's patent expiry. Further, we show in a functionally specified model‐based illustration, involving varying combinations of plausible ratios of OTC and Rx version margins and potential market sizes, that denial of OTC market exclusivity can imply that the firm should advance rather than delay the partial switch, and yield greater savings for Rx drug consumers. Implications for pharmaceutical Rx–OTC switch planners and policymakers are discussed.
Interaction of NiSi with dopants for metallic source/drain applications
Authors: Luo Jun , Qiu Zhi-Jun , Zhang Zhen , Östling Mikael , Zhang Shi-Li
Published: March 2010

This work has a focus on NiSi as a possible metallic contact for aggressively scaled complementary metal oxide semiconductor devices. As the bulk work function of NiSi lies close to the middle of Si bandgap, the Schottky barrier height (SBH) of NiSi is rather large for both electron (∼0.65eV) and hole (∼0.45eV). Different approaches have therefore been intensively investigated in the literature aiming at reducing the effective SBH: dopant segregation (DS), surface passivation (SP), and alloying, in order to improve the carrier injection into the conduction channel of a field-effect transistor. The present work explores DS using B and As for the NiSi∕Si contact system. The effects of C and N implantation into Si substrate prior to the NiSi formation are examined, and it is found that the presence of C yields positive effects in helping reduce the effective SBH to 0.1–0.2eV for both conduction polarities. A combined use of DS or SP with alloying could be considered for more effective control of effective SBH, but an examination of undesired compound formation and its probable consequences is necessary. Furthermore, an analysis of the metal silicides that have a small “intrinsic” SBH reveals that only a very small number of them are of practical interest as most of the silicides require either a high formation temperature or possess a high specific resistivity.
Plasma kinetics of Ar/O2 magnetron discharge by two-dimensional multifluid modeling
Authors: Costin C. , Minea T. M. , Popa G. , Gousset G.
Published: March 2010

Multifluid two-dimensional model was developed to describe the plasma kinetics of the direct current Ar/O2 magnetron, coupling two modules: charged particles and neutrals. The first module deals with three positive ions—Ar+, O2+, and O+—and two negative species—e− and O−—treated by the moments of Boltzmann’s equation. The second one follows seven neutral species (Ar, O2, O, O3, and related metastables) by the multicomponent diffusion technique. The two modules are self-consistently coupled by the mass conservation and kinetic coefficients taking into account more than 100 volume reactions. The steady state is obtained when the overall convergence is achieved. Calculations for 10% O2 in Ar/O2 mixture at 2.67 and 4 Pa show that the oxygen excited species are mainly created by electron collisions in the negative glow of the discharge. Decreasing the pressure down to 0.67 Pa, the model reveals the nonlocal behavior of the reactive species. The density gradient of O2 ground state is reversed with respect to all gradients of the other reactive species, since the latter ones originate from the molecular ground state of oxygen. It is also found that the wall reactions drastically modify the space gradient of neutral reactive species, at least as much as the pressure, even if the discharge operates in compound mode.
Deglacial Meltwater Pulse 1B and Younger Dryas Sea Levels Revisited with Boreholes at Tahiti
Authors: Bard Edouard , Hamelin Bruno , Delanghe-Sabatier Doriane
Published: March 2010

Episodic Rise

Sea-level rise between the end of the Last Glacial Maximum and the beginning of the Holocene accelerated episodically, with the fastest rate occurring during meltwater pulse 1A (14,000 years ago) and perhaps during another interval called meltwater pulse 1B (11,300 years ago). However, existing records are not precise enough to confidently assess sea-level change during meltwater pulse 1B or the Younger Dryas cold event (12,900 to 11,600 years ago).

Bard
et al.

(p.
1235
, published online 14 January) present data from three cores drilled in coral reefs in Tahiti that allow a better quantification of sea-level changes between 14,000 and 9000 years ago. No significant change in the rate of sea-level rise could be detected for the period previously identified as meltwater pulse 1B; reducing the likelihood that such an episode occurred. Furthermore, sea level rose more rapidly at the start of the Younger Dryas but slowed during the rest of the cold event. These findings have implications for our understanding of the dynamics of deglaciation.
Romantics in the English Manner
The Age of Wonder
How the Romantic Generation Discovered the Beauty and Terror of Science

by Richard Holmes

Harper, London, 2008. 600 pp. £25, C$55.95. ISBN 9780007149520. Pantheon, New York, 2009. $40. ISBN 9780375422225. Paper, Harper, London, 2009. £9.99, C$21.95. ISBN 9780007149537. Vintage, New York, 2010. $17.95. ISBN 9781400031870.
Authors: Richards Robert J.
Published: March 2010

Holmes has woven an engaging narrative from tales of English scientists in the decades around 1800.
RTEL-1 Enforces Meiotic Crossover Interference and Homeostasis
Authors: Youds Jillian L. , Mets David G. , McIlwraith Michael J. , Martin Julie S. , Ward Jordan D. , ONeil Nigel J. , Rose Ann M. , West Stephen C. , Meyer Barbara J. , Boulton Simon J.
Published: March 2010

Managing Crossovers

In all sexual eukaryotes a special type of cell division called meiosis produces gametes or spores. For chromosomes to segregate properly to the daughter cells during meiosis, DNA crossovers must occur between every pair of homologous chromosomes. The position and number of these crossovers, which help to hold the homologous chromosomes together, is carefully controlled, in part by the condensin I complex.

Youds
et al.

(p.
1254
) show that in the nematode,
Caenorhabditis elegans
, crossovers are regulated at a second level by the anti-recombinase RTEL-1 (regulator of telomere elongation helicase–1). RTEL-1 prevents crossovers occurring too close to each other, and ensures that only one occurs per pair of homologous chromosomes.
Calibrating the Cryogenian
Authors: Macdonald Francis A. , Schmitz Mark D. , Crowley James L. , Roots Charles F. , Jones David S. , Maloof Adam C. , Strauss Justin V. , Cohen Phoebe A. , Johnston David T. , Schrag Daniel P.
Published: March 2010

Aging Snowball Earth

Earth's glacial cycles have varied dramatically over time; at one point glaciers may have covered nearly the entire planet. Correlating various paleoclimate proxies such as fossil and isotope records from that time hinges on the ability to acquire precise age estimates of rocks deposited around the time of this so-called “Snowball Earth.”

Macdonald
et al.

(p.
1241
) report new high-precision U-Pb dates of Neoproterozoic strata in the Yukon and Northwest Territories, Canada, to calibrate the timing of carbon isotope variation in rocks from other locations around the globe. Based on the estimated past positions of where these rocks were deposited, glaciers probably extended to equatorial latitudes. The overlap with the survival and, indeed, diversification of some eukaryotes in the fossil record suggests that life survived in localized ecological niches during this global glaciation.
Geodynamo, Solar Wind, and Magnetopause 3.4 to 3.45 Billion Years Ago
Authors: Tarduno John A. , Cottrell Rory D. , Watkeys Michael K. , Hofmann Axel , Doubrovine Pavel V. , Mamajek Eric E. , Liu Dunji , Sibeck David G. , Neukirch Levi P. , Usui Yoichi
Published: March 2010

Early Origin of Earth's Magnetic Field

Earth's magnetic field protects us from stellar winds and radiation from the Sun. Understanding when, during the Earth's formation, the large-scale magnetic field was established is important because it impacts understanding of the young Earth's atmosphere and exosphere. By analyzing ancient silicate crystals,

Tarduno
et al.

(p.
1238
; see the Perspective by

Jardine

) demonstrate that the Earth's magnetic field existed 3.4 to 3.45 billion years ago, pushing back the oldest record of geomagnetic field strength by 200 million years. This result combined with estimates of the conditions within the solar wind at that time implies that the size of the paleomagnetosphere was about half of that typical today, but with an auroral oval of about three times the area. The smaller magnetosphere and larger auroral oval would have promoted loss of volatiles and water from the early atmosphere.
Comment on “Movement Intention After Parietal Cortex Stimulation in Humans”
Authors: Karnath Hans-Otto , Borchers Svenja , Himmelbach Marc
Published: March 2010

Desmurget
et al
. (Reports, 8 May 2009, p. 811) applied direct electrical stimulation (DES) to the human cortex to study the origin of movement intention. Their interpretation assumed that DES causes cortical activation, whereas it is possible that it actually evokes deactivation. The lack of certain knowledge about the true effects of DES limits its use for validation of cognitive models.
Hippocampal Short- and Long-Term Plasticity Are Not Modulated by Astrocyte Ca
2+
Signaling
Authors: Agulhon Cendra , Fiacco Todd A. , McCarthy Ken D.
Published: March 2010

Reexamining Glial Function

In the last 20 years glial cells have been elevated from being considered as passive elements during neuronal transmission. By eliciting astroglial calcium rises, so-called gliotransmitters such as glutamate, ATP, or
d
-serine can be released and the activity of neighboring neurons modulated. However, this emerging picture has been challenged.

Agulhon
et al.

(p.
1250
; see the Perspective by

Kirchhoff

) reexamined these questions using two previously characterized mouse models. Calcium elevations induced selectively in astrocytes caused no change in multiple measures of synaptic activity. Furthermore, in mutant mice unable to elevate intracellular calcium, all synaptic measures were at wild-type levels. Astrocytic calcium signaling activity was thus not tied to the release of gliotransmitters and didn't affect synaptic transmission, short and long-term synaptic plasticity.
Two Years Later, New Rumblings Over Origins of Sichuan Quake
Authors: Kerr Richard A. , Stone Richard
Published: March 2010

Scientists in China say they've ruled out reservoir triggering in the disastrous 2008 Wenchuan earthquake. But many earth scientists don't buy their arguments.
Of Two Minds About Toba's Impact
Authors: Balter Michael
Published: March 2010

Researchers gathered at a meeting last month to probe the impact on modern humans of the cataclysmic eruption of Indonesia's Mount Toba about 74,000 years ago—and to ponder whether modern humans had made it to Asia by the time the volcano blew.
Semiconductors Inspire New Sequencing Technologies
Authors: Pennisi Elizabeth
Published: March 2010

In a packed house at the final Saturday session of the annual Advances in Genome Biology and Technology meeting, revolutionary new DNA-sequencing technologies using silicon wafers and quantum dots were presented.
Aggregation of
Streptococcus pneumoniae
by a Pneumococcal Capsular Polysaccharide-Specific Human Monoclonal IgM Correlates with Antibody Efficacy
In Vivo
Authors: Fabrizio Kevin , Manix Catherine , Guimaraes̃ Allan J. , Nosanchuk Joshua D. , Pirofski Liise-anne
Published: March 2010

Acquired antibody immunity to
Streptococcus pneumoniae
(pneumococcus) has been linked to serotype (ST)-specific opsonic antibodies to the relevant pneumococcal capsular polysaccharide (PPS) that mediate protection by enhancing the bactericidal effect of host phagocytes. Despite the well-recognized role of opsonic IgG in host defense against pneumococcus, PPS-specific monoclonal antibodies (MAbs) that mediate protection against lethal challenge with ST3 pneumococcus in mice but do not promote phagocytic killing
in vitro
(nonopsonic antibodies) have been described. In this study, we sought to determine the biological activity of one such MAb, A7 (a human PPS3-specific IgM), and the mechanism by which it mediates protection.
In vitro
studies demonstrated that coincubation of A7 with ST3 in the absence of phagocytes or a complement source resulted in a reduction in CFU on blood agar plates that was largely reversible by sonication. A chromogenic cellular proliferation assay demonstrated that A7 did not affect replication of ST3 in liquid culture. The ability of A7 to induce aggregation of ST3 was confirmed by fluorescence microscopy and flow cytometry: A7 induced aggregation of ST3, and in the presence of a complement source, A7 promoted deposition of complement component 3 (C3) on aggregated bacteria in a dose-dependent fashion. Similarly, administration of preincubated mixtures of A7 and ST3 intraperitoneally to mice protected them from the lethality of ST3 in a dose-dependent fashion. These findings suggest that A7-mediated aggregation enhances resistance to ST3, most likely by enhancing C3 deposition on the ST3 capsule, thereby promoting host antipneumococcal activity
in vivo
.
Glucose-Based Peritoneal Dialysis Fluids Downregulate Toll-Like Receptors and Trigger Hyporesponsiveness to Pathogen-Associated Molecular Patterns in Human Peritoneal Mesothelial Cells
Authors: Wu Jun , Yang Xiao , Zhang Yun-Fang , Wang Ya-Ning , Liu Mei , Dong Xiu-Qing , Fan Jin-Jin , Yu Xue-Qing
Published: March 2010

The objective of this study was to investigate the effects of glucose-based peritoneal dialysis (PD) fluids and icodextrin-based PD fluids on the expression of Toll-like receptor 2 (TLR2)/TLR4 and subsequent ligand-induced mitogen-activated protein kinase (MAPK) and NF-κB signaling and tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) mRNA expression in human peritoneal mesothelial cells (HPMCs). A human peritoneal mesothelial cell line (HMrSV5) was stimulated with glucose-based and icodextrin-based peritoneal dialysis fluids. Cell viability was assessed using MTT [3-(4,5-dimethylthiazolyl)-2,5-diphenyl-2H-tetrazolium bromide]. TLR2/TLR4 expression was determined by real-time PCR, Western blotting, and an immunofluorescence assay. In addition, cells were pretreated with different PD solutions and then incubated with Pam3CSK4 or lipopolysaccharide (LPS), and the degrees of MAPK and NF-κB activation were reflected by detecting the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38, and p65, using a Western blot method. TNF-α and IL-1β mRNA expression was measured by real-time PCR. Glucose-based peritoneal dialysis fluids suppressed the expression of TLR2 and TLR4 proteins in HPMCs. Challenge of cells with either Pam3CSK4 or LPS resulted in impaired TNF-α and IL-1β production. Moreover, reduced TLR2 and TLR4 levels in glucose-based peritoneal dialysis solution-treated mesothelial cells were accompanied by reduced p42/44 (ERK1/2), JNK, p38 MAPK, and NF-κB p65 phosphorylation upon TLR ligand engagement. No significant changes in MAPK and NF-κB signaling and TNF-α and IL-1β mRNA expression were observed in icodextrin-based PD solution-treated mesothelial cells. Glucose-based PD solution, but not icodextrin-based PD solution, downregulates expression of TLR2/TLR4 by human peritoneal mesothelial cells and triggers hyporesponsiveness to pathogen-associated molecular patterns.
Evaluation of Molecular Tools for Detection and Drug Susceptibility Testing of
Mycobacterium tuberculosis
in Stool Specimens from Patients with Pulmonary Tuberculosis
Authors: Cordova Julianna , Shiloh Ron , Gilman Robert H. , Sheen Patricia , Martin Laura , Arenas Fanny , Caviedes Luz , Kawai Vivian , Soto Giselle , Williams Diana L. , Zimic Mirko , Escombe A. Roderick , Evans Carlton A.
Published: March 2010

Pulmonary tuberculosis diagnosis is difficult when patients cannot produce sputum. Most sputum is swallowed, and tuberculosis DNA can survive intestinal transit. We therefore evaluated molecular testing of stool specimens for detecting tuberculosis originating from the lungs. Paired stool and sputum samples (
n
= 159) were collected from 89 patients with pulmonary tuberculosis. Control stool samples (
n
= 47) were collected from patients without tuberculosis symptoms. Two techniques for DNA extraction from stool samples were compared, and the diagnostic accuracy of the PCR in stool was compared with the accuracy of sputum testing by PCR, microscopy, and culture. A heminested IS
6110
-PCR was used for tuberculosis detection, and IS
6110
-PCR-positive stool samples then underwent rifampin sensitivity testing by universal heteroduplex generator PCR (heteroduplex-PCR) assay. For newly diagnosed pulmonary tuberculosis patients, stool IS
6110
-PCR had 86% sensitivity and 100% specificity compared with results obtained by sputum culture, and stool PCR had similar sensitivities for HIV-positive and HIV-negative patients (
P
= 0.3). DNA extraction with commercially available spin columns yielded greater stool PCR sensitivity than DNA extraction with the in-house Chelex technique (
P
= 0.007). Stool heteroduplex-PCR had 98% agreement with the sputum culture determinations of rifampin resistance and multidrug resistance. Tuberculosis detection and drug susceptibility testing by stool PCR took 1 to 2 days compared with an average of 9 weeks to obain those results by traditional culture-based testing. Stool PCR was more sensitive than sputum microscopy and remained positive for most patients for more than 1 week of treatment. In conclusion, stool PCR is a sensitive, specific, and rapid technique for the diagnosis and drug susceptibility testing of pulmonary tuberculosis and should be considered when sputum samples are unavailable.
Comparison of the Plating Efficiencies and Shelf Lives of Three Different Commercial Buffered Charcoal Yeast Extract Media Supplemented with α-Ketoglutaric Acid
Authors: Edelstein Paul H. , Edelstein Martha A. C.
Published: March 2010

The plating efficiencies and shelf lives of locally made buffered charcoal yeast extract medium supplemented with α-ketoglutaric acid (BCYEα) were compared to those of media made by BD, Hardy, and Remel. Lung homogenates from guinea pigs infected with
Legionella pneumophila
were plated monthly onto different medium lots. All media performed equally well and had shelf lives of at least 12 months.