bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term storage limits PCR-based analyses of malaria parasites in archival dried blood spots
Authors: Hwang Joyce , Jaroensuk Juthamas , Leimanis Mara L , Russell Bruce , McGready Rose , Day Nicholas , Snounou George , Nosten Francois , Imwong Mallika
Published: October 2012

Background

Blood samples collected in epidemiological and clinical investigations and then stored, often at room temperature, as blood spots dried on a filter paper have become one of the most popular source of material for further molecular analyses of malaria parasites. The dried blood spots are often archived so that they can be used for further retrospective investigations of parasite prevalence, or as new genetic markers come to the fore. However, the suitability of the template obtained from dried blood spots that have been stored for long periods for DNA amplification is not known.

Methods

DNA from 267 archived blood spots collected over a period of 12 years from persons with microscopically confirmed Plasmodium falciparum infection was purified by one of two methods, Chelex and Qiagen columns. These templates were subjected to highly sensitive nested PCR amplification targeting three parasite loci that differ in length and/or copy number.

Results

When a 1.6 kb fragment of the parasites’ small subunit ribosomal RNA was targeted (primary amplification), the efficiency of P. falciparum detection decreased in samples archived for more than six years, reaching very low levels for those stored for more than 10 years. Positive amplification was generally obtained more often with Qiagen-extracted templates. P. falciparum could be detected in 32 of the 40 negative Qiagen-extracted templates when a microsatellite of about 180 bp was targeted. The remaining eight samples gave a positive amplification when a small region of 238 bp of the higher copy number (20 to 200) mitochondrial genome was targeted.

Conclusions

The average length of DNA fragments that can be recovered from dried blood spots decreases with storage time. Recovery of the DNA is somewhat improved, especially in older samples, by the use of a commercial DNA purification column, but targets larger than 1.5 kb are unlikely to be present 10 years after the initial blood collection, when the average length of the DNA fragments present is likely to be around a few hundred bp. In conclusion, the utility of archived dried blood spots for molecular analyses decreases with storage time.
The alveolar epithelial differentiation of glandular inner lining cells in a mucoepidermoid carcinoma of the lung: a case report
Authors: Xu Hong-Tao , Lin Xu-Yong , Li Qing-Chang , Wang En-Hua
Published: October 2012

Mucoepidermoid carcinoma is a common malignant epithelial tumor of salivary glands, but relatively rare in lung. The histological features of mucoepidermoid carcinoma of the lung are similar to its counterpart arising from the salivary glands. Here, we reported a special tumor that occurred in the medial segment of the right lower lobe in a 22-year-old man. This tumor exhibited typical features of mucoepidermoid carcinoma with 3 cell types: squamoid cells, mucin-secreting cells and cells of intermediate type. These 3 types of cells organized into cysts, nests, glands and solid patterns. Specially, the inner lining cells of some glandular structures were uniform cuboidal and hobnail-like, similar to the alveolar epithelial cells. Immunohistochemistry staining revealed that the inner lining cells of glandular structures were positive for thyroid transcription factor-1 and surfactant protein-B, used as markers of alveolar epithelial cells, and were negative for p63. These findings for the first time demonstrated a rare alveolar epithelial differentiation of glandular inner lining cells in a mucoepidermoid carcinoma of the lung.

Virtual Slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/7095988968057804
Osteomyelitis and pyoarthritis resulting from local paracoccidioidomycosis in an immunocompetent patient: a case report
Authors: Michelan Michel Santana , Fernandes Eloy de Ávila , Freitas Leonardo Furtado , Ribeiro Rodrigo Hoeller , Milano Marília Magri , Monteiro Soraya Silveira
Published: October 2012

Introduction

Paracoccidioidomycosis is a type of mycosis that is endemic to Brazil and is triggered by the fungus Paracoccidioides brasiliensis. Isolated bone involvement in this disease is very rare, especially in children. To the best of our knowledge this report documents the first case of an immunocompetent pediatric patient in which paracoccidioidomycosis of the hip articulation was the sole manifestation of the disease (that is, there were no pulmonary or skin lesions).

Case presentation

An 11-year-old Brazilian Caucasian boy from a rural area was examined in the orthopedic ward of our emergency department. Our patient reported a three-month history of pain in the right hip with intermittent claudication and also complained of recurring episodes of intense pain and an inability to walk, which he had been experiencing for the previous five days. He additionally presented with a fever that had persisted for two days. Our patient’s medical history did not include any clinical respiratory manifestations, skin lesions, history of trauma or immunosuppression risk factors.

Conclusions

This is one of the very few reported cases of isolated articular involvement in osteomyelitis in a pediatric immunocompetent patient. Paracoccidioidomycosis should be considered among the differential diagnoses in such cases, especially in cases of patients who reside in rural areas where the condition is considered to be endemic, in order to administer the proper course of treatment in a timely fashion and improve the chances of a favorable prognosis.
Mitochondrial dysfunction associated with increased oxidative stress and α-synuclein accumulation in PARK2 iPSC-derived neurons and postmortem brain tissue
Authors: Imaizumi Yoichi , Okada Yohei , Akamatsu Wado , Koike Masato , Kuzumaki Naoko , Hayakawa Hideki , Nihira Tomoko , Kobayashi Tetsuro , Ohyama Manabu , Sato Shigeto , Takanashi Masashi , Funayama Manabu , Hirayama Akiyoshi , Soga Tomoyoshi , Hishiki Takako , Suematsu Makoto , Yagi Takuya , Ito Daisuke , Kosakai Arifumi , Hayashi Kozo , Shouji Masanobu , Nakanishi Atsushi , Suzuki Norihiro , Mizuno Yoshikuni , Mizushima Noboru , Amagai Masayuki , Uchiyama Yasuo , Mochizuki Hideki , Hattori Nobutaka , Okano Hideyuki
Published: October 2012

Background

Parkinson’s disease (PD) is a neurodegenerative disease characterized by selective degeneration of dopaminergic neurons in the substantia nigra (SN). The familial form of PD, PARK2, is caused by mutations in the parkin gene. parkin-knockout mouse models show some abnormalities, but they do not fully recapitulate the pathophysiology of human PARK2.

Results

Here, we generated induced pluripotent stem cells (iPSCs) from two PARK2 patients. PARK2 iPSC-derived neurons showed increased oxidative stress and enhanced activity of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. iPSC-derived neurons, but not fibroblasts or iPSCs, exhibited abnormal mitochondrial morphology and impaired mitochondrial homeostasis. Although PARK2 patients rarely exhibit Lewy body (LB) formation with an accumulation of α-synuclein, α-synuclein accumulation was observed in the postmortem brain of one of the donor patients. This accumulation was also seen in the iPSC-derived neurons in the same patient.

Conclusions

Thus, pathogenic changes in the brain of a PARK2 patient were recapitulated using iPSC technology. These novel findings reveal mechanistic insights into the onset of PARK2 and identify novel targets for drug screening and potential modified therapies for PD.
Protocol-directed insulin infusion sliding scales improve perioperative hyperglycaemia in critical care
Authors: Hui Man Lin , Kumar Arun , Adams Gary G
Published: October 2012

Perioperative hyperglycaemia is associated with poor outcomes in patients undergoing cardiac surgery. Frequent postoperative hyperglycaemia in cardiac surgery patients has led to the initiation of an insulin infusion sliding scale for quality improvement.

A systematic review was conducted to determine whether a protocol-directed insulin infusion sliding scale is as safe and effective as a conventional practitioner-directed insulin infusion sliding scale, within target blood glucose ranges.

A literature survey was conducted to identify reports on the effectiveness and safety of an insulin infusion protocol, using seven electronic databases from 2000 to 2012: MEDLINE, CINAHL, EMBASE, the Cochrane Library, the Joanna Briggs Institute Library and SIGLE. Data were extracted using pre-determined systematic review and meta-analysis criteria.

Seven research studies met the inclusion criteria. There was an improvement in overall glycaemic control in five of these studies. The implementation of protocols led to the achievement of blood glucose concentration targets more rapidly and the maintenance of a specified target blood glucose range for a longer time, without any increased frequency of hyperglycaemia. Of the seven studies, four used controls and three had no controls.

In terms of the meta-analysis carried out, four studies revealed a failure of patients reaching target blood glucose levels (P< 0.0005) in the control group compared with patients in the protocol group. The risk of hypoglycaemia was significantly reduced (P<0.00001) between studies.

It can be concluded that the protocol-directed insulin infusion sliding scale is safe and improves blood glucose control when compared with the conventional practitioner-directed insulin infusion sliding scale. This study supports the adoption of a protocol-directed insulin infusion sliding scale as a standard of care for post-cardiac surgery patients.
Migration velocity analysis for TI media in the presence of quadratic lateral velocity variation
Authors: Takanashi Mamoru , Tsvankin Ilya
Published: October 2012

One of the most serious problems in anisotropic velocity analysis is the trade-off between anisotropy and lateral heterogeneity, especially if velocity varies on a scale smaller than the maximum offset. We have developed a P-wave MVA (migration velocity analysis) algorithm for transversely isotropic (TI) models that include layers with small-scale lateral heterogeneity. Each layer is described by constant Thomsen parameters [Formula: see text] and [Formula: see text] and the symmetry-direction velocity [Formula: see text] that varies as a quadratic function of the distance along the layer boundaries. For tilted TI media (TTI), the symmetry axis is taken orthogonal to the reflectors. We analyzed the influence of lateral heterogeneity on image gathers obtained after prestack depth migration and found that quadratic lateral velocity variation in the overburden can significantly distort the moveout of the target reflection. Consequently, medium parameters beneath the heterogeneous layer(s) are estimated with substantial error, even when borehole information (e.g., check shots or sonic logs) is available. Because residual moveout in the image gathers is highly sensitive to lateral heterogeneity in the overburden, our algorithm simultaneously inverts for the interval parameters of all layers. Synthetic tests for models with a gently dipping overburden demonstrate that if the vertical profile of the symmetry-direction velocity [Formula: see text] is known at one location, the algorithm can reconstruct the other relevant parameters of TI models. The proposed approach helps increase the robustness of anisotropic velocity model-building and enhance image quality in the presence of small-scale lateral heterogeneity in the overburden.
Canid Progesterone Receptors Lack Activation Function 3 Domain-Dependent Activity
Authors: Gracanin Ana , van Wolferen Monique E. , Sartorius Carol A. , Brenkman Arjan B. , Schoonen Willem G. , Mol Jan A.
Published: October 2012

Progesterone regulates multiple behavioral, physiological, and pathological aspects of female reproductive biology through its two progesterone receptors (PRs), PR-B and the truncated PR-A. PR-B is necessary for mammary gland development in mice and, compared with PR-A, is overall a stronger transactivator of target genes due to an additional activation function 3 (AF3) domain. In dogs, known for their high sensitivity to progesterone-induced mammary cancer, the PR-B function was studied. Canine PR (cPR)-B appeared to contain multiple mutations within AF3 core sequence motifs and lacks N-terminal ligand-independent posttranslational modifications. Consequently, cPR-B has a weak transactivation potential on progesterone-responsive mouse mammary tumor virus-luc and progesterone response element 2-luc reporters transiently transfected in hamster, human, or canine cells and also on known target genes FKBP5 and SGK in doxycycline-inducible, stable transfected cPR-B in canine mammary cells. The cPR-B function was restored to the level of human PR-B by the replacement of canine AF3 domain with the human one. The lack of AF3 domain-dependent transcriptional activity was unique for canids (gray wolf, red fox, and raccoon dog) and not present in closely related caniform species (brown bear, gray seal, and domestic ferret). Despite the limited transactivation potential, canids develop normal mammary glands and frequently mammary tumors. Therefore, these results question the role of PR-B in breast cancer development and may explain unique features of canid reproduction.
Nuclear Export Signal of Androgen Receptor (NESAR) Regulation of Androgen Receptor Level in Human Prostate Cell Lines via Ubiquitination and Proteasome-Dependent Degradation
Authors: Gong Yanqing , Wang Dan , Dar Javid A. , Singh Prabhpreet , Graham Lara , Liu Weijun , Ai Junkui , Xin Zhongcheng , Guo Yinglu , Wang Zhou
Published: October 2012

Androgen receptor (AR) plays a key role in prostate development and carcinogenesis. Increased expression and/or stability of AR is associated with sensitization of prostate cancer cells to low levels of androgens, leading to castration resistance. Hence, understanding the mechanisms regulating AR protein stability is clinically relevant and may lead to new approaches to prevent and/or treat prostate cancer. Using fluorescence microscopy, Western blot, and pulse chase assay, we showed that nuclear export signal (NES)AR, a nuclear export signal in the ligand binding domain (LBD) of AR, can significantly enhance the degradation of fusion protein constructs in PC3 prostate cancer cells. The half-life of GFP-NESAR was less than 3 h, which was 10 times shorter than that of green fluorescent protein (GFP) control. Further analysis showed that NESAR can signal for polyubiquitination and that degradation of NESAR-containing fusion proteins can be blocked by proteasome inhibitor MG132. Ubiquitination of GFP-AR or GFP-LBD was suppressed in the presence of dihydrotestosterone, which is known to suppress NESAR while inducing nuclear localization signal 2 in AR or LBD, suggesting that the export activity of NESAR is required for NESAR-mediated polyubiquitination. Treatment with MG132 also induced aggresome formation of NESAR-containing fusion proteins in perinuclear regions of the transfected PC3 cells, indicating a role for NESAR in inducing unfolded protein responses. The above observations suggest that NESAR plays a key role in AR ubiquitination and proteasome-dependent degradation in prostate cancer cells.
A Clinical Prediction Score to Diagnose Unilateral Primary Aldosteronism
Authors: Küpers Elselien M. , Amar Laurence , Raynaud Alain , Plouin Pierre-François , Steichen Olivier
Published: October 2012

Context:

Adrenal venous sampling is recommended to assess whether aldosterone hypersecretion is lateralized in patients with primary aldosteronism. However, this procedure is invasive, poorly standardized, and not widely available.

Objective:

Our goal was to identify patients' characteristics that can predict unilateral aldosterone hypersecretion in some patients who could hence bypass adrenal venous sampling before surgery.

Design and Setting:

A cross-sectional diagnostic study was performed from February 2009 to July 2010 at a single center specialized in hypertension care.

Patients:

A total of 101 consecutive patients with primary aldosteronism who underwent adrenal venous sampling participated in the study. The autonomy of aldosterone hypersecretion was assessed with the saline infusion test.

Intervention:

Adrenal venous sampling was performed without ACTH infusion but with simultaneous bilateral sampling.

Main Outcome Measures:

Variables independently associated with a lateralized adrenal venous sampling in multivariate logistic regression were used to derive a clinical prediction rule.

Results:

Adrenal venous sampling was successful in 87 patients and lateralized in 49. All 26 patients with a typical Conn's adenoma plus serum potassium of less than 3.5 mmol/liter or estimated glomerular filtration rate of at least 100 ml/min/1.73 m2 (or both) had unilateral primary aldosteronism; this rule had 100% specificity (95% confidence interval, 91–100) and 53% sensitivity (95% confidence interval, 38–68).

Conclusions:

If our results are validated on an independent sample, adrenal venous sampling could be omitted before surgery in patients with a typical Conn's adenoma if they meet at least one of two supplementary biochemical characteristics (serum potassium <3.5 mmol/liter or estimated glomerular filtration rate ≥100 ml/min/1.73 m2).
Down-Regulation of S100A11, a Calcium-Binding Protein, in Human Endometrium May Cause Reproductive Failure
Authors: Liu Xin-Mei , Ding Guo-Lian , Jiang Ying , Pan Hong-Jie , Zhang Dan , Wang Ting-Ting , Zhang Run-Ju , Shu Jing , Sheng Jian-Zhong , Huang He-Feng
Published: October 2012

Background:

Low expression levels of S100A11 proteins were demonstrated in the placental villous tissue of patients with early pregnancy loss, and S100A11 is a Ca2+-binding protein that interprets the calcium fluctuations and elicits various cellular responses.

Objectives:

The objective of the study was to determine S100A11 expression in human endometrium and its roles in endometrial receptivity and embryo implantation.

Methods:

S100A11 expression in human endometrium was analyzed using quantitative RT-PCR, Western blot, and immunohistochemical techniques. The effects of S100A11 on embryo implantation were examined using in vivo mouse model, and JAr (a human choriocarcinoma cell line) spheroid attachment assays. The effects of endometrial S100A11 on factors related to endometrial receptivity and immune responses were examined. Using a fluorescence method, we examined the changes in cytosolic Ca2+ and Ca2+ release from intracellular stores in epidermal growth factor (EGF)-treated endometrial cells transfected with or without S100A11 small interfering RNA.

Results:

S100A11 was expressed in human endometrium. S100A11 protein levels were significantly lower in endometrium of women with failed pregnancy than that in women with successful pregnancy outcomes. The knockdown of endometrial S100A11 not only reduced embryo implantation rate in mouse but also had adverse effects on the expression of factors related to endometrial receptivity and immune responses in human endometrial cells. Immunofluorescence analysis showed that S100A11 proteins were mainly localized in endoplasmic reticulum. The EGF up-regulated endometrial S100A11 expression and promoted the Ca2+ uptake and release from Ca2+ stores, which was inhibited by the knockdown of S100A11.

Conclusions:

Endometrial S100A11 is a crucial intermediator in EGF-stimulated embryo adhesion, endometrium receptivity, and immunotolerance via affecting Ca2+ uptake and release from intracellular Ca2+ stores. Down-regulation of S100A11 may cause reproductive failure.
Vildagliptin Reduces Glucagon during Hyperglycemia and Sustains Glucagon Counterregulation during Hypoglycemia in Type 1 Diabetes
Authors: Farngren Johan , Persson Margaretha , Schweizer Anja , Foley James E. , Ahrén Bo
Published: October 2012

Context:

The dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits glucagon secretion at hyperglycemia but appears to enhance glucagon counterregulation during hypoglycemia in type 2 diabetes.

Objective:

The objective of the investigation was to study whether vildagliptin also improves α-cell function in type 1 diabetes (T1D).

Patients and Methods:

The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 28 patients with C-peptide negative and antibody positive T1D [21 males, seven females, glycosylated hemoglobin 57.9 mmol/mol (7.5%)]. Patients received vildagliptin (50 mg twice a day) or placebo as an add-on to their insulin therapy for 4 wk each. On d 28 of the respective treatment period, patients were served a standard meal (500 kcal) to raise the circulating incretin hormone levels followed by a hyperinsulinemic hypoglycemic clamp at 2.5 mmol/liter.

Main Outcome Measure:

The increase in plasma glucagon levels during the 30-min hypoglycemic clamp (min 165–195 of the test) was measured.

Results:

During the meal, glucagon levels were lower with vildagliptin than with placebo (120 min area under the curveglucagon 2.4 ± 0.2 vs. 2.6 ± 0.2 nmol/liter × minutes, P = 0.022 for between group difference). In contrast, during hypoglycemia, the glucagon counterregulation was not reduced by vildagliptin (increase in glucagon 1.5 ± 1.0 pmol/liter with vildagliptin vs. 1.7 ± 0.8 pmol/liter with placebo, P = NS). In addition, the counterregulatory responses in epinephrine, norepinephrine, cortisol, and pancreatic polypeptide were not different between the treatments. During the 4-wk treatment period, vildagliptin reduced the mean glycosylated hemoglobin, whereas there was no change with placebo [between group difference was −3.4 ± 1.0 mmol/mol (−0.32 ± 0.09%; P = 0.002)] from baseline of 57.9 mmol/mol (7.5%).

Conclusions:

Vildagliptin, although inhibiting glucagon secretion during hyperglycemia, does not compromise the glucagon counterregulatory response during hypoglycemia in T1D.
Longitudinal Assessment of Bone Density and Structure in Childhood Survivors of Acute Lymphoblastic Leukemia without Cranial Radiation
Authors: Mostoufi-Moab Sogol , Brodsky Jill , Isaacoff Elizabeth J. , Tsampalieros Anne , Ginsberg Jill P. , Zemel Babette , Shults Justine , Leonard Mary B.
Published: October 2012

Purpose:

Children with acute lymphoblastic leukemia (ALL) are at risk for impaired bone accrual. This peripheral quantitative computed tomography study assessed changes in bone mineral density (BMD) and structure after completion of ALL treatment.

Methods:

Fifty ALL participants, ages 5–22 yr, were enrolled within 2 yr (median 0.8 yr) after completing ALL therapy. Tibia peripheral quantitative computed tomography scans were performed at enrollment and 12 months later. Age-, sex-, and race-specific Z-scores for trabecular BMD (TrabBMD), cortical BMD (CortBMD), and cortical area (CortArea) were generated based on more than 650 reference participants. Multivariable linear regression models examined determinants of changes in Z-scores.

Results:

At enrollment, mean TrabBMD (−1.03 ± 1.34) and CortBMD (−0.84 ± 1.05) Z-scores were low (both P < 0.001) compared with reference participants. TrabBMD and CortBMD Z-scores increased to −0.58 ± 1.41 and −0.51 ± 0.91 over 1 yr, respectively (both P < 0.001). Changes in cortical outcomes varied according to the interval since completion of therapy. Among those enrolled less than 6 months after therapy, CortArea Z-scores increased and CortBMD Z-scores decreased (both P < 0.01). Among those enrolled 6 months or more after therapy, CortArea Z-scores did not change and CortBMD Z-scores increased (P < 0.01). Changes in CortArea and CortBMD Z-scores were inversely associated (r = −0.32, P < 0.001). Cumulative glucocorticoid exposure, leukemia risk status, and antimetabolite chemotherapy were not associated with outcomes.

Conclusion:

TrabBMD was low after completion of ALL therapy and improved significantly. Early increases in cortical dimensions were associated with declines in CortBMD; however, participants further from ALL therapy demonstrated stable cortical dimensions and increases in CortBMD, potentially reflecting the time necessary to mineralize newly formed bone.
Glucocorticoid Replacement and Mortality in Patients with Nonfunctioning Pituitary Adenoma
Authors: Zueger Thomas , Kirchner Paul , Herren Coline , Fischli Stefan , Zwahlen Marcel , Christ Emanuel , Stettler Christoph
Published: October 2012

Context:

Current treatment guidelines generally suggest using lower and weight-adjusted glucocorticoid replacement doses in patients with insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis. Although data in patients with acromegaly revealed a positive association between glucocorticoid dose and mortality, no comparable results exist in patients with nonfunctioning pituitary adenomas (NFPA).

Objective:

Our objective was to assess whether higher glucocorticoid replacement doses are associated with increased mortality in patients with NFPA and HPA axis insufficiency.

Design, Participants, and Intervention:

We included 105 patients receiving glucocorticoid replacement after pituitary surgery due to NFPA and concomitant HPA axis insufficiency. Patients were grouped according weight-adapted and absolute hydrocortisone (HC) replacement doses. Mortality was assessed using Kaplan-Meier methodology as well as multivariable Cox regression models.

Setting:

This was a retrospective analysis conducted at a tertiary referral center.

Main Outcome:

We evaluated overall mortality based on HC replacement doses.

Results:

Average age at inclusion was 58.9 ± 14.8 yr, and mean follow-up was 12.7 ± 9.4 yr. The groups did not differ according to age, follow-up time, pattern of hypopituitarism, and comorbidities. Kaplan-Meier survival probabilities differed significantly when comparing individuals with differing weight-adjusted HC dose (P = 0.001) as well as absolute HC dose (5–19, 20–29, and ≥30 mg, P = 0.009). Hazard ratios for mortality increased from 1 (0.05–0.24 mg/kg) to 2.62 (0.25–0.34 mg/kg) to 4.56 (≥0.35 mg/kg, P for trend = 0.006) and from 1 (5–19 mg) to 2.03 (20–29 mg) to 4 (≥30 mg, P for trend = 0.029), respectively.

Conclusion:

Higher glucocorticoid replacement doses are associated with increased overall mortality in patients with NFPA and insufficiency of HPA axis. This further substantiates the importance of a balanced and adjusted glucocorticoid replacement therapy in these patients.
The medico-legal significance of pharmacokinetic interactions with ethanol
Authors: Langford N J , Ferner R E
Published: October 2012

In the UK, the maximal permitted ethanol concentration for driving is 80 mg ethanol/100 mL blood, 35 μg ethanol/100 mL breath or 107 mg ethanol/100 mL urine. Drivers exceeding the prescribed limit face severe penalties, which they are often anxious to avoid, either by acquittal or by putting forward ‘special reasons’ why they should not be disqualified from driving. One frequently explored defence is that the accused was taking prescribed medication. Defence solicitors often ask the question whether the prescribed medication could have caused significantly altered blood ethanol concentrations. This paper reviews the impact of various medications and how they can influence the blood ethanol concentration. Although many drugs can interact with ethanol at a pharmacodynamic level, causing increased impairment, relatively few drugs interact with ethanol pharmacokinetically leading to significantly altered blood ethanol concentrations.
Contracting Information Security in the Presence of Double Moral Hazard
Authors: Lee Chul Ho , Geng Xianjun , Raghunathan Srinivasan
Published: October 2012

In information security outsourcing, it is the norm that the outsourcing firms and the outsourcers (commonly called managed security service providers, MSSPs) need to coordinate their efforts for better security. Nevertheless, efforts are often private and thus both firms and MSSPs can suffer from double moral hazard. Furthermore, the double moral hazard problem in security outsourcing is complicated by the existence of strong externality and the multiclient nature of MSSP services. In this prescriptive research, we first show that the prevailing contract structure in security outsourcing, bilateral refund contract, cannot solve double moral hazard. Adding breach-contingent sunk cost or external payment cannot solve double moral hazard either. Furthermore, positive externality can worsen double moral hazard. We then propose a new contract structure termed multilateral contract and show that it can solve double moral hazard and induce first-best efforts from all contractual parties when an MSSP serves two or more client firms, regardless of the externality. Firm-side externality significantly affects how payments flow under a multilateral contract when a security breach happens. When the number of client firms for an MSSP increases, we show that the contingent payments under multilateral contracts for any security breach scenario can be easily calculated using an additive method, and thus are computationally simple to implement.
IT Implementation Contract Design: Analytical and Experimental Investigation of IT Value, Learning, and Contract Structure
Authors: Wu D. J. , Ding Min , Hitt Lorin M.
Published: October 2012

This article analytically and experimentally investigates how firms can best capture the business value of information technology (IT) investments through IT contract design. Using a small sample of outsourcing contracts for enterprise information technology (EIT) projects in several industries—coupled with reviews of contracts used by a major enterprise software maker—the authors determine the common provisions and structural characteristics of EIT contracts. The authors use these characteristics to develop an analytical model of optimal contract design with principal–agent techniques. The model captures a set of key characteristics of EIT contracts, including a staged, multiperiod project structure; learning; probabilistic binary outcomes; variable fee structures; possibly risk-averse agents; and implementation risks. The model characterizes conditions under which multistage contracts enable clients to create and capture greater project value than single-stage projects, and how project staging enables firms to reduce project risks, capture learning benefits, and increase development effort. Finally, the authors use controlled laboratory experiments to complement their analytical approaches and demonstrate robustness of their key findings.
Delegation vs. Control of Component Procurement Under Asymmetric Cost Information and Simple Contracts
Authors: Kayış Enis , Erhun Feryal , Plambeck Erica L.
Published: October 2012

A manufacturer must choose whether to delegate component procurement to her tier 1 supplier or control it directly. Because of information asymmetry about suppliers' production costs and the use of simple quantity discount or price-only contracts, either delegation or control can yield substantially higher expected profit for the manufacturer. Delegation tends to outperform control when (1) the manufacturer is uncertain about the tier 1 supplier's cost and believes that it is likely to be high; (2) the manufacturer and the tier 1 supplier know the tier 2 supplier's cost or at least that it will be high; (3) the manufacturer has an alternative to engaging the tier 1 and tier 2 suppliers, such as in-house production; and (4) the firms use price-only contracts as opposed to quantity discount contracts. These results shed light on practices observed in the electronics industry.
Aligning Capacity Decisions in Supply Chains When Demand Forecasts Are Private Information: Theory and Experiment
Authors: Hyndman Kyle , Kraiselburd Santiago , Watson Noel
Published: October 2012

We study the problem of a two-firm supply chain in which firms simultaneously choose a capacity before demand is realized. We focus on the role that private information about demand has on firms' ability to align their capacity decisions. When forecasts are private information, there are at most two equilibria: a complete coordination failure or a monotone equilibrium. The former equilibrium always exists, whereas the latter exists only when the marginal cost of capacity is sufficiently low. We also show that both truthful information sharing and preplay communication have an equilibrium with higher profits. We then test the model's predictions experimentally. Contrary to our theoretical predictions, we show that private demand forecasts do not have a consistently negative effect on firm profits, though capacities are more misaligned. We show that preplay communication may be more effective at increasing profits than truthful information sharing. Finally, we document that “honesty is the best policy” when communicating private information.
Strategic Queueing Behavior and Its Impact on System Performance in Service Systems with the Congestion-Based Staffing Policy
Authors: Guo Pengfei , Zhang Zhe George
Published: October 2012

We study strategic customer behavior in a multiserver stochastic service system with a congestion-based staffing (CBS) policy. With the CBS policy, the number of working servers is dynamically adjusted according to the queue length. Besides lining up for free service, customers have the option of paying a fee and getting faster service. Customers' equilibrium behavior is studied under two information scenarios: In the no information scenario, customers only know the long-term statistics, such as the expected waiting time; in the partial information scenario, customers observe the number of working servers and understand the staffing policy upon their arrival. Unlike a queueing system with a constant staffing level, a positive externality is associated with customers' joining the CBS system. Both avoid-the-crowd and follow-the-crowd customer behaviors are possible, and multiple equilibria could exist. We develop the stationary performance measures of the system by considering the customers' strategic behavior. Numerical analysis shows that information can either hurt or improve the performance of the system, depending on the staffing and pricing policy. Another important conclusion is that the system performance is more robust to setting a relatively high than a relatively low price.
On the Equilibrium Behavior of a Supply Chain Market for Capacity
Authors: Sapra Amar , Jackson Peter L.
Published: October 2012

Acapacity market is a business-to-business exchange in which equally capable suppliers compete with one another to satisfy generic orders from diverse buyers. The market is asymmetric because the buyers can carry inventory of the products ordered but the suppliers cannot store their capacity. In such a market, we might expect to see something like a price for capacity emerge to equilibrate demand and supply. The financial risk of participating in such a market will be driven by the volatility of the capacity price. In this paper we develop a model to explore the behavior of such a market and demonstrate, for example, that volatility of the price for capacity increases, to a point, when inflexibility of the capacity increases. We can also make statements about how the resolution of price uncertainty in the capacity market is related to the resolution of demand uncertainty faced by the buyers. Another contribution of the paper is to explain the role of market characteristics in how the market acts to minimize shortages caused by consumer demand uncertainty. We use continuous time stochastic optimal control techniques and numerical experiments to demonstrate these insights.
REVIEWS
Authors: Mavor James , Pennacchia Maddalena , Raw Laurence
Published: October 2012

SCRIPTWRITING FOR THE SCREEN, CHARLIE MORITZ (2008) Oxon: Routledge, 220 pp., ISBN 13: 978-0-415-46517-5, p/bk, £18.99

THE ENCHANTED SCREEN. THE UNKNOWN HISTORY OF FAIRY-TALE FILMS, JACK ZIPES (2011) New York: Routledge, 435 pp., ISBN978-0-415-99061-5, p/bk, $49.95

THE
ADAPTAION INDUSTRY: THE CULTURAL ECONOMY OF CONTEMPORARY LITERARY ADAPTATION, SIMONE MURRAY (2012) New York and London: Routledge, 253 pp., ISBN 978-0-415-99903-8, £80.00
Freeze-frame: The death and life of a photograph in Mitko Panov's With Raised Hands
Authors: Marx Lesley
Published: October 2012

This article will analyse the relationship, reflexively dramatized by With Raised Hands, between still and moving images, taking into account the ambiguous way in which photographs record and memorialize both life and death. This ambiguity is especially charged, historically
and psychically, when the photograph registers a traumatic – and now iconic – encounter.
With Raised Hands, a web of tensions
Authors: Lefebvre-Linetzky Jacques
Published: October 2012

Resorting to moving images, Mitko Panov brings to life an iconic photograph. The spectator is confronted with a web of tensions involving time and space. It is a reconstruction that compels the viewer to measure the impact of an image that was not originally intended to arouse compassion.
Subjective and objective point of view as metaphor in Mitko Panov's With Raised Hands
Authors: Anderson Kevin
Published: October 2012

What are we watching here? What is the nature of our discomfort? The point of view established in the opening of With Raised Hands – through the lens of a German camera recording the round-up of Jews in the Warsaw Ghetto – uncomfortably implicates us in this act of
violence. The subsequent shifts in point of view are also supported by temporal shifts, both of which function at deeper, metaphorical levels to support the developing story.
Sublimity, the sacred and violence in Wind
Authors: Kerner Aaron Michael
Published: October 2012

Wind evokes the ideas present in Roland Barthes's Camera Lucida. The film also approaches the sublime in its audio design and its depiction of space, and at the end invites us to consider the relationship between violence and the sacred.
The Moore film adaptations and the erotic-grotesque
Authors: Dawe Ian
Published: October 2012

The grotesque, a staple of the comic book vernacular is a defining characteristic of Alan Moore's graphic literature. Moore's work often transcends the traditional grotesque and blends this aesthetic with erotic elements, evoking the subversive spirit of the carnival, foregrounding
bodily transformation, deformation and the connection between interior bodily functions and the external world. Bakhtin describes this 'festival of the body' as essential to an understanding of the literary and artistic carnivalesque. Moore's literary take on the erotic-grotesque adds resonance
to some of his central themes such as invisible connections between class, gender, social groups and moral opposites. His artistic collaborators have expressed this effectively throughout Moore's literary oeuvre. Unfortunately, the film adaptations of Moore's work tend to de-emphasize
this critical aspect. I assert that the artistic success or failure of the Moore film adaptations rest to a large extent on the degree to which they grapple with the erotic-grotesque. From Hell (2001), which I argue is the most successful cinematic adaptation of Moore's literature in
these terms, retains the essence of Moore's erotic-grotesque sensibilities even while altering much of the principal narrative and themes. By contrast, the film adaptation of The League of Extraordinary Gentlemen (2003) also alters the narrative and characterization to a great extent,
but also removes much of the novel's sense of the erotic-grotesque. This omission, I argue, is the key element that leads to the film's relative artistic failure. A truly satisfying cinematic adaptation of a Moore novel, therefore, must embrace this key element of his literature.
From Hell: Examining the transition from page to screen
Authors: Young Áine
Published: October 2012

Alan Moore and the Hughes brothers shared a common goal to depict nineteenth-century English slum life in a credible manner in their versions of From Hell. The documentary style created by Moore and Eddie Campbell in their graphic novel is not replicated in the film with correspondent
solutions specific to cinema. Instead, the Hughes brothers veered away from the source text thematically and aesthetically, creating something quite different. These choices, although inventive, ultimately alienated fans and were a factor in the film's moderate critical reception. Pascal Lefevre
posits in his essay 'Incompatible Visual Ontologies?' that the unique conflicts facing a film-making team that choose to adapt a comic book can be broken down into four main divisions: 'first, to what extent the screenwriter has to rewrite the story, second, how to go from page layout to a
single, unchangeable screen frame, third, how to translate the static drawings into moving and photographic images, and fourth, how to give the "silent world" an audible sound?'. These distinctions will frame my theoretical, thematic and aesthetic analysis of Alan Moore's graphic novel From
Hell to the resultant film of the same name.
Chronic Chagas disease: from basics to laboratory medicine
Authors: Haberland Annekathrin , Munoz Saravia Silvia Gilka , Wallukat Gerd , Ziebig Reinhard , Schimke Ingolf
Published: October 2012

Chagas disease, caused byTrypanosoma cruziinfection, is ranked as the most serious parasitic disease in Latin America and has huge potential to become a worldwide problem, due to increasing migration, and international tourism, as well as infectant transfer by blood contact and transfusion, intrauterine transfer, and organ transplantation. Nearly 30% of chronically-infected patients become symptomatic, often with a latency of 10–30 years, developing life-threatening complications. Of those, nearly 90% develop Chagas heart disease, while the others manifest gastrointestinal disease and neuronal disorders. Besides interrupting the infection cycle and chemotherapeutic infectant elimination, starting therapy early in symptomatic patients is important for counteracting the disease. This would be essentially supported by optimized patient management, involving risk assessment, early diagnosis and monitoring of the disease and its treatment. From economic and logistic viewpoints, the tools of laboratory medicine should be especially able to guarantee this. After summarizing the basics of chronic Chagas disease, such as the epidemiological data, the pathogenetic mechanisms thought to drive symptomatic Chagas disease and also treatment options, we present tools of laboratory medicine that address patient diagnosis, risk assessment for becoming symptomatic and guidance, focusing on autoantibody estimation for risk assessment and heart marker measurement for patient guidance. In addition, increases in levels of inflammation and oxidative stress markers in chronic Chagas disease are discussed.
Hydrolytic enzyme activity of EN113 standard basidiomycetes in the fermentation of lignocellulosic material and wood colonization
Authors: Elisashvili Vladimir , Irbe Ilze , Andersone Ingeborga , Andersons Bruno , Tsiklauri Nino
Published: October 2012

The white-rot fungusTrametes versicolorand brown-rot fungiConiophora puteana,Gloeophyllum trabeum, andPostiaplacentahave a potential to produce a range of hydrolytic enzymes participating in the degradation of lignocellulosic materials. In the colonization of untreated and thermally modified wood blocks wheat bran-containing medium (WBA) greatly favored the secretion of xylanase byC. puteanaand both endoglucanase and xylanase expression byT. versicolor, although rather higher carboxymethyl cellulase activity ofC. puteanawas observed on the malt extract-based medium (malt extract-containing agar (MEA).Coniophora puteanaandT. versicolorare able to actively colonize and degrade the untreated pine and birch wood blocks. The mycelium applied on blocks in the form of pellets was more aggressive in wood degradation in comparison with the colonized mycelium. WBA favored the dry matter loss during the initial stages (10–20 days) of pine wood colonization; however, MEA further promoted more rapid wood degradation. The main finding was that the thermal treatment of birch wood was accompanied by a low degree of fungal colonization and increased durability against the fungal attack in spite of the high cellulase and xylanase activities. Thermal modification of wood was not toxic to the fungi because it did not disturb the secretion of the hydrolytic enzymes involved in wood degradation. The thermally modified hollocellulose is probably less susceptible to the enzymes involved in the degradation of polysaccharides or less accessible to hydrolytic enzymes due to the change of the cell wall structure.
Comparative evaluation of different kinetic models for batch cooking: A review
Authors: Nieminen Kaarlo , Sixta Herbert
Published: October 2012

The purpose of this study was to review some of the existing models for delignification in kraft cooking. Data and results from earlier studies were utilized to evaluate the performance of the models of Gustafson (MG), Purdue (MP), Andersson (MA) and Bogren’s method “continuous distribution of reactivity” (MBcdr) in terms of their ability to give a realistic description for delignification of softwood and hardwood. The MG, MP and MBcdr were tested on lignin data obtained from cooks of Eucalyptus globulus. In this case, MP seemed to perform best, whereas the MBcdr failed in the range of low residual lignins. MA considers the lignin subunits with various reaction speeds, and this feature improves the performance in the case of low residual lignins and helps to reflect sudden changes in cooking conditions, but the difference to the ordinary MP is moderate.
Determination of metal ions in single wood fiber by LA-ICP-MS
Authors: Su Pingping , Ek Paul , Ivaska Ari
Published: October 2012

Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was used to determine the distribution of metal elements in single wood fiber of kraft pulp. Calibration procedures for quantitative analysis of metals in single fibers (SFs) by LA-ICP-MS technique were also developed. Calibration curves were constructed by using matrix-matched standards prepared from (a) cellulose powder washed with 0.05 M EDTA, (b) unbleached softwood pulp washed with 0.05 M EDTA and nitric acid. Calibration materials were prepared by doping the washed cellulose powder and the washed unbleached softwood pulp with standard solutions with increasing concentrations of the elements of interest (Co, Mg, Cu, Na, K, Mn, Zn, Ni, Ca, and Fe). Quantitative determination of the metals in single wood fiber was based on the calibration curves resulting from both the doped cellulose pellets and the doped SFs. The determination of the absolute concentration of elements in a single wood fiber by LA-ICP-MS is still difficult, but in this study, it was demonstrated that the information about the metal distribution can be obtained easily, and their semiquantitative determination is possible.
Optical properties of thermomechanical pulp (TMP) obtained from sulfite-pretreated Norway spruce with focus on two-photon spectral imaging (TPSI)
Authors: Hafrén Jonas , Nelsson Erik , Gerritsen Hans C. , Bader Arjen N.
Published: October 2012

Chips of Norway spruce have been impregnated with Na2SO3 and refined at two specific energy consumptions levels at full mill scale. The optical properties of thermomechanical pulps (TMPs) obtained were analyzed in terms of brightness, light scattering, opacity, and autofluorescence by spectral imaging. Even at low sulfite dosage (0.24% sulfite by dry weight) light absorption was reduced, and the brightness was elevated, and a clear dose-response effect was observed. Two-photon spectral imaging (TPSI) showed that sulfonation, impregnation, and refining affect the fluorescence properties differently. Compared to native wood, both processed wood chips and pulp fibers revealed blue-shifted fluorescence maxima, a characteristic of shortened conjugated systems. Two subpopulations of fibers with different optical properties were observed, and the fluorescence of one fiber population was red shifted.