bluuebunny/crossref_metadata_2025 huggingface dataset:
Budget impact analysis of ustekinumab in the management of moderate to severe psoriasis in Greece
Authors: Avgerinou Georgia , Bassukas Ioannis , Chaidemenos Georgios , Katsampas Andreas , Kosmadaki Marita , Kousoulakou Hara , Petridis Athanasios , Schenkel Brad , Sotiriadis Dimitrios , Spiliopoulos Theofanis , Stavropoulos Panagiotis , Toumpi Evgenia , Xaplanteris Loukas
Published: July 2012

Background

The purpose of this study was to estimate the annual and per-patient budget impact of the treatment of moderate to severe psoriasis in Greece before and after the introduction of ustekinumab.

Methods

A budget impact model was constructed from a national health system perspective to depict the clinical and economic aspects of psoriasis treatment over 5 years. The model included drug acquisition, monitoring, and administration costs for both the induction and maintenance years for patients in a treatment mix with etanercept, adalimumab, infliximab, with or without ustekinumab. It also considered the resource utilization for non-responders. Greek treatment patterns and resource utilization data were derived from 110 interviews with dermatologists conducted in February 2009 and evaluated by an expert panel of 18 key opinion leaders. Officially published sources were used to derive the unit costs. Costs of adverse events and indirect costs were excluded from the analysis. Treatment response was defined as the probability of achieving a PASI 50, PASI 75, or PASI 90 response, based on published clinical trial data.

Results

The inclusion of ustekinumab in the biological treatment mix for moderate to severe psoriasis is predicted to lead to total per-patient savings of €443 and €900 in years 1 and 5 of its introduction, respectively. The cost savings were attributed to reduced administration costs, reduced hospitalizations for non-responders, and improved efficacy. These results were mainly driven by the low number of administrations required with ustekinumab over a 5 year treatment period (22 for ustekinumab, compared with 272 for etanercept, 131 for adalimumab, and 36 for infliximab).

Conclusions

The inclusion of ustekinumab in the treatment of moderate to severe psoriasis in Greece is anticipated to have short- and long-term health and economic benefits, both on an annual and per-patient basis.
A stepwise approach for the reproducible optimization of PAMO expression in Escherichia coli for whole-cell biocatalysis
Authors: van Bloois Edwin , Dudek Hanna M , Duetz Wouter A , Fraaije Marco W
Published: July 2012

Background

Baeyer-Villiger monooxygenases (BVMOs) represent a group of enzymes of considerable biotechnological relevance as illustrated by their growing use as biocatalyst in a variety of synthetic applications. However, due to their increased use the reproducible expression of BVMOs and other biotechnologically relevant enzymes has become a pressing matter while knowledge about the factors governing their reproducible expression is scattered.

Results

Here, we have used phenylacetone monooxygenase (PAMO) from Thermobifida fusca, a prototype Type I BVMO, as a model enzyme to develop a stepwise strategy to optimize the biotransformation performance of recombinant E. coli expressing PAMO in 96-well microtiter plates in a reproducible fashion. Using this system, the best expression conditions of PAMO were investigated first, including different host strains, temperature as well as time and induction period for PAMO expression. This optimized system was used next to improve biotransformation conditions, the PAMO-catalyzed conversion of phenylacetone, by evaluating the best electron donor, substrate concentration, and the temperature and length of biotransformation. Combining all optimized parameters resulted in a more than four-fold enhancement of the biocatalytic performance and, importantly, this was highly reproducible as indicated by the relative standard deviation of 1% for non-washed cells and 3% for washed cells. Furthermore, the optimized procedure was successfully adapted for activity-based mutant screening.

Conclusions

Our optimized procedure, which provides a comprehensive overview of the key factors influencing the reproducible expression and performance of a biocatalyst, is expected to form a rational basis for the optimization of miniaturized biotransformations and for the design of novel activity-based screening procedures suitable for BVMOs and other NAD(P)H-dependent enzymes as well.
Superior semicircular canal dehiscence in East Asian women with osteoporosis
Authors: Yu Alexander , Teich Douglas L , Moonis Gul , Wong Eric T
Published: July 2012

Background

Superior semicircular canal dehiscence (SSCD) may cause Tullio phenomenon (sound-induced vertigo) or Hennebert sign (valsalva-induced vertigo) due to the absence of bone overlying the SSC. We document a case series of elderly East Asian women with atypical SSCD symptoms, radiologically confirmed dehiscence and concurrent osteoporosis.

Methods

A retrospective record review was performed on patients with dizziness, vertigo, and/or imbalance from a neurology clinic in a community health center serving the East Asian population in Boston. SSCD was confirmed by multi-detector, high-resolution CT of the temporal bone (with Pöschl and Stenvers reformations) and osteoporosis was documented by bone mineral density (BMD) scans.

Results

Of the 496 patients seen in the neurology clinic of a community health center from 2008 to 2010, 76 (17.3%) had symptoms of dizziness, vertigo, and/or imbalance. Five (6.6%) had confirmed SSCD by multi-detector, high-resolution CT of the temporal bone with longitudinal areas of dehiscence along the long axis of SSC, ranging from 0.4 to 3.0 mm, as seen on the Pöschl view. Two of the 5 patients experienced motion-induced vertigo, two fell due to disequilibrium, and one had chronic dizziness. None had a history of head trauma, otologic surgery, or active intracerebral disease. On neurological examination, two patients had inducible vertigo on Dix-Hallpike maneuver and none experienced cerebellar deficit, Tullio phenomenon, or Hennebert sign. All had documented osteoporosis or osteopenia by BMD scans. Three of them had definite osteoporosis, with T-scores < −2.5 in the axial spine, while another had osteopenia with a T-score of −2.3 in the left femur.

Conclusions

We describe an unusual presentation of SSCD without Tullio phenomenon or Hennebert sign in a population of elderly, East Asian women. There may be an association of SSCD and osteoporosis in this population. Further research is needed to determine the incidence and prevalence of this disorder, as well as the relationship of age, race, osteoporosis risk, and the development of SSCD.
Some results of certain types of difference and differential equations
Authors: Liu Yong , Cao Yin Hong , Yi Hong Xun
Published: July 2012

In this article, we shall utilize the value distribution theory and complex oscillation theory to investigate certain types of difference and differential equations. The results we obtain generalize some previous results of Gundersen and Yang.

MSC:30D35, 34M10.
Development of one-step TaqMan® real-time reverse transcription-PCR and conventional reverse transcription-PCR assays for the detection of equine rhinitis A and B viruses
Authors: Lu Zhengchun , Timoney Peter J , White Jena , Balasuriya Udeni BR
Published: July 2012

Background

Equine rhinitis viruses A and B (ERAV and ERBV) are common equine respiratory viruses belonging to the family Picornaviridae. Sero-surveillance studies have shown that these two viral infections are prevalent in many countries. Currently, the diagnosis of ERAV and ERBV infections in horses is mainly based on virus isolation (VI). However, the sensitivity of VI testing varies between laboratories due to inefficient viral growth in cell culture and lack of cytopathic effect. Therefore, the objective of this study was to develop molecular diagnostic assays (real-time RT-PCR [rRT-PCR] and conventional RT-PCR [cRT-PCR] assays) to detect and distinguish ERAV from ERBV without the inherent problems traditionally associated with laboratory diagnosis of these infections.

Results

Three rRT-PCR assays targeting the 5'-UTR of ERAV and ERBV were developed. One assay was specific for ERAV, with the two remaining assays specific for ERBV. Additionally, six cRT-PCR assays targeting the 5'-UTR and 3D polymerase regions of ERAV and ERBV were developed. Both rRT-PCR and cRT-PCR assays were evaluated using RNA extracted from 21 archived tissue culture fluid (TCF) samples previously confirmed to be positive for ERAV (n = 11) or ERBV (n = 10) with mono-specific rabbit antisera. The ERAV rRT-PCR and cRT-PCR assays could only detect ERAV isolates and not ERBV isolates. Similarly, the ERBV rRT-PCR and cRT-PCR assays could only detect ERBV isolates and not ERAV isolates. None of the rRT-PCR or cRT-PCR assays cross-reacted with any of the other common equine respiratory viruses. With the exception of one cRT-PCR assay, the detection limit of all of these assays was 1 plaque forming unit per ml (pfu/ml).

Conclusion

The newly developed rRT-PCR and cRT-PCR assays provide improved diagnostic capability for the detection and differentiation of ERAV and ERBV. However, a larger number of clinical specimens will need to be tested before each assay is adequately validated for the detection of ERAV and/or ERBV in suspect cases of either viral infection.
Luminal A and luminal B (HER2 negative) subtypes of breast cancer consist of a mixture of tumors with different genotype
Authors: Yanagawa Masumi , Ikemot Kenzo , Kawauchi Shigeto , Furuya Tomoko , Yamamoto Shigeru , Oka Masaaki , Oga Atunori , Nagashima Yukiko , Sasaki Kohsuke
Published: July 2012

Background

The St Gallen International Expert Consensus 2011 has proposed a new classification system for breast cancer. The purpose of this study was to elucidate the relationship between the breast cancer subtypes determined by the new classification system and genomic characteristics.

Methods

Invasive breast cancers (n = 363) were immunohistochemically classified as follows: 111 (30.6%) as luminal A, 95 (26.2%) as luminal B (HER2 negative), 69 (19.0%) as luminal B (HER2 positive), 41 (11.3%) as HER2, and 47 (12.9%) as basal-like subtypes.

Results

The high expression of Ki-67 antigen was detected in 236 tumors; no cases of luminal A subtype showed high expression of the Ki-67 antigen, but more than 85% of tumors of the other subtypes showed high expression. In addition, DNA ploidy and chromosomal instability (CIN) were assessed using imaging cytometry and FISH, respectively. In this series, 336 (92.6%) tumors consisted of 129 diploid/CIN- and 207 aneuploid/CIN + tumors. Diploid/CIN- and aneuploid/CIN+ features were detected in 64.9% and 27.9% of luminal A, 41.1% and 49.5% of luminal B (HER2-), 11.6% and 81.2% of luminal B (HER2+), 4.9% and 90.2% of HER2, and 17.0% and 76.6% of basal-like subtypes, respectively. Unlike the luminal B (HER2+), HER2 and basal-like subtypes, the luminal A and luminal B (HER2-) subtypes were heterogeneous in terms of DNA ploidy and CIN.

Conclusions

It is reasonable to propose that the luminal A and luminal B (HER2-) subtypes should be further divided into two subgroups, diploid/CIN- and aneuploid/CIN+, based on their underlying genomic status.
Comparison of seasonal variation in the fasting respiratory quotient of young Japanese, Polish and Thai women in relation to seasonal change in their percent body fat
Authors: Morinaka Tomoko , Wozniewicz Malgorzata , Jeszka Jan , Bajerska Joanna , Limtrakul Porn-ngarm , Makonkawkeyoon Luksana , Hirota Naoko , Kumagai Shoko , Sone Yoshiaki
Published: July 2012

Background

From the viewpoint of human physiological adaptability, we previously investigated seasonal variation in the amount of unabsorbed dietary carbohydrates from the intestine after breakfast in Japanese, Polish and Thai participants. In this investigation we found that there were significant seasonal variations in the amount of unabsorbed dietary carbohydrates in Japanese and Polish participants, while we could not find significant seasonal variation in Thai participants. These facts prompted us to examine seasonal variations in the respiratory quotient after an overnight fast (an indicator of the ratio of carbohydrate and fat oxidized after the last meal) with female university students living in Osaka (Japan), Poznan (Poland) and Chiang Mai (Thailand).

Methods

We enrolled 30, 33 and 32 paid participants in Japan, Poland and Thailand, respectively, and measurements were taken over the course of one full year. Fasting respiratory quotient was measured with the participants in their postabsorptive state (after 12 hours or more fasting before respiratory quotient measurement). Respiratory quotient measurements were carried out by means of indirect calorimetry using the mixing chamber method. The percent body fat was measured using an electric bioelectrical impedance analysis scale. Food intake of the participants in Osaka and Poznan were carried out by the Food Frequency Questionnaire method.

Results

There were different seasonal variations in the fasting respiratory quotient values in the three different populations; with a significant seasonal variation in the fasting respiratory quotient values in Japanese participants, while those in Polish and Thai participants were non-significant. We found that there were significant seasonal changes in the percent body fat in the three populations but we could not find any significant correlation between the fasting respiratory quotient values and the percent body fat.

Conclusions

There were different seasonal variations in the fasting respiratory quotient values in the three different populations. There were significant seasonal changes in the percent body fat in the three populations but no significant correlation between the fasting respiratory quotient values and the percent body fat.
Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer
Authors: Kim Jisun , Han Wonshik , Moon Hyeong-Gon , Ahn Soo Kyung , Shin Hee-Chul , You Jee-Man , Han Sae-Won , Im Seock-Ah , Kim Tae-You , Koo Hye Ryoung , Chang Jung Min , Cho Nariya , Moon Woo Kyung , Noh Dong-Young
Published: July 2012

Introduction

Anti-estrogen therapy has been shown to reduce mammographic breast density (MD). We hypothesized that a short-term change in breast density may be a surrogate biomarker predicting response to adjuvant endocrine therapy (ET) in breast cancer.

Methods

We analyzed data for 1,065 estrogen receptor (ER)-positive breast cancer patients who underwent surgery between 2003 and 2006 and received at least 2 years of ET, including tamoxifen and aromatase inhibitors. MD was measured using Cumulus software 4.0 and expressed as a percentage. MD reduction (MDR) was defined as the absolute difference in MD of mammograms taken preoperatively and 8-20 months after the start of ET.

Results

At a median follow-up of 68.8 months, the overall breast cancer recurrence rate was 7.5% (80/1065). Mean MDR was 5.9% (range, -17.2% to 36.9%). Logistic regression analysis showed that age < 50 years, high preoperative MD, and long interval between start of ET to follow-up mammogram were significantly associated with larger MDR (p < 0.05). In a survival analysis, tumor size, lymph node positivity, high Ki-67 (≥ 10%), and low MDR were independent factors significantly associated with recurrence-free survival (p < 0.05). Compared with the group showing the greatest MDR (≥ 10%), the hazard ratios for MDRs of 5-10%, 0-5%, and < 0% were 1.33, 1.92, and 2.26, respectively.

Conclusions

MD change during short-term use of adjuvant ET was a significant predictor of long-term recurrence in women with ER-positive breast cancer. Effective treatment strategies are urgently needed in patients with low MDR despite about 1 year of ET.
Short-range homing in a site-specific fish: search and directed movements
Authors: Mitamura Hiromichi , Uchida Keiichi , Miyamoto Yoshinori , Kakihara Toshiharu , Miyagi Aki , Kawabata Yuuki , Ichikawa Kotaro , Arai Nobuaki
Published: July 2012

Sedentary and territorial rockfish of the genus Sebastes exhibit distinctive homing ability and can travel back to an original location after displacements of metres or even kilometres. However, little is known about the behavioural and sensory mechanisms involved in homing. Although our previous study demonstrated that nocturnal black rockfish Sebastes cheni predominantly use their olfactory sense for homing from an unfamiliar area, the possibility of using landmarks in a familiar area cannot be discounted; i.e. site-specific fish are likely to use three-dimensional spatial memory for navigation and orientation. Using high-resolution acoustic telemetry, we investigated whether S. cheni exhibit distinctive homing paths. Results show that all of the eight rockfish increased their effort within a small area of an unfamiliar region around the release site just after displacement, suggesting that the rockfish probably searched for the homeward direction. The rockfish showed the search movement in the upstream and/or downstream direction, which did not lead home. Finally, after returning to their familiar area, the rockfish exhibited more directed movements with faster speeds at a shallower depth, which was similar to the depth utilised in daily life as well as that of the fish capture.
The role of endogenous H2S formation in reversible remodeling of lung tissue during hibernation in the Syrian hamster
Authors: Talaei Fatemeh , Bouma Hjalmar R. , Hylkema Machteld N. , Strijkstra Arjen M. , Boerema Ate S. , Schmidt Martina , Henning Rob H.
Published: July 2012

During hibernation, small mammals alternate between periods of metabolic suppression and low body temperature (‘torpor’) and periods of full metabolic recovery with euthermic temperatures (‘arousal’). Previously, we demonstrated marked structural remodeling of the lung during torpor, which is rapidly reversed during arousal. We also found that cooling of hamster cells increased endogenous production of H2S through the enzyme cystathionine-β-synthase (CBS). H2S suppresses the immune response and increases deposition of collagen. Therefore, we examined inflammatory markers and matrix metalloproteinase (MMP) activity in relation to CBS expression and H2S levels in lungs of euthermic and hibernating Syrian hamsters. Lung remodeling during torpor was confirmed by a strong increase in both collagenous and non-collagenous hydroxyproline content. The number of leukocytes in lung was unchanged in any phase of hibernation, while adhesion molecules VCAM-1 and ICAM-1, and the inflammatory marker NF-κB (P65) were modestly upregulated in torpor. Gelatinase activity was decreased in lungs from torpid animals, indicating inhibition of the Zn2+-dependent MMP-2 and MMP-9. Moreover, expression of CBS and tissue levels of H2S were increased in torpor. All changes normalized during arousal. Inhibition of gelatinase activity in torpor is likely caused by quenching of Zn2+ by the sulphide ion of H2S. In accord, inhibition of CBS normalized gelatinase activity in torpid animals. Conversely, NaHS decreased the gelatinase activity of euthermic animals, which was attenuated by excess Zn2+. Similar results were obtained on the activity of the Zn2+-dependent angiotensin converting enzyme. Our data indicate that increased production of H2S through CBS in hamster lungs during torpor contributes to remodeling by inhibition of gelatinase activity and possibly by suppression of the inflammatory response. Although administration of H2S is known to induce metabolic suppression in non-hibernating mammals (‘suspended animation’), this is the first report implying endogenous H2S production in natural hibernation.
The relative cost of using luminescence for sex and defense: light budgets in cypridinid ostracods
Authors: Rivers Trevor J. , Morin James G.
Published: July 2012

Luminescent signals can be used by animals for a number of purposes, including courtship and defense, sometimes by the same individual. However, the relative costs of producing these different behaviors are largely unknown. In the marine ostracod Photeros annecohenae, males utilize extracellular luminescence for complex courtship displays, and both males and females luminesce as a predation defense. We compared the relative luminescent output of courtship with that of defensive displays and also with respect to their total luminescent stores. Courtship displays are relatively inexpensive compared with defensive displays, with an average defensive display releasing 50 times more luminescence than the average courtship display. Furthermore, in order to completely exhaust its stores, a male would have to produce 450 typical courtship displays or approximately 10 average defensive displays. Both courtship pulses and defensive displays show first-order decay kinetics, yet courtship pulses decay three times faster than defensive displays, suggesting that there is differential release of the luciferin, luciferase and mucus in order to control the reaction kinetics.
Flies dynamically anti-track, rather than ballistically escape, aversive odor during flight
Authors: Wasserman Sara , Lu Patrick , Aptekar Jacob W. , Frye Mark A.
Published: July 2012

Tracking distant odor sources is crucial to foraging, courtship and reproductive success for many animals including fish, flies and birds. Upon encountering a chemical plume in flight, Drosophila melanogaster integrates the spatial intensity gradient and temporal fluctuations over the two antennae, while simultaneously reducing the amplitude and frequency of rapid steering maneuvers, stabilizing the flight vector. There are infinite escape vectors away from a noxious source, in contrast to a single best tracking vector towards an attractive source. Attractive and aversive odors are segregated into parallel neuronal pathways in flies; therefore, the behavioral algorithms for avoidance may be categorically different from tracking. Do flies plot random ballistic or otherwise variable escape vectors? Or do they instead make use of temporally dynamic mechanisms for continuously and directly avoiding noxious odors in a manner similar to tracking appetitive ones? We examine this question using a magnetic tether flight simulator that permits free yaw movements, such that flies can actively orient within spatially defined odor plumes. We show that in-flight aversive flight behavior shares all of the key features of attraction such that flies continuously ‘anti-track’ the noxious source.
A spurious haemoglobin A1c result associated with double heterozygote for haemoglobin Raleigh (β1[NA1]Val → Ala) and α+-thalassaemia
Authors: Singha Kritsada , Fucharoen Goonnapa , Chaibunruang Attawut , Netnee Paripat , Fucharoen Supan
Published: July 2012

Background

Accurate measurement of haemoglobin A1c (HbA1c) is useful for long-term glycaemic control in patients with diabetes. Many Hb variants can interfere with HbA1c measurement and cause inaccurate results.

Methods

The subject was a 31-year-old Thai man who was discovered because of an unexpected HbA1c result; other diabetic parameters were within the normal range. Abnormal Hb was investigated using automated high-pressure liquid chromatography (HPLC) and a capillary electrophoresis system. Mutation analysis was done by cDNA sequencing, polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and multiplex allele-specific PCR assays.

Results

Evaluation of HbA1c by cation-exchange HPLC showed a value of 34.9% (reference interval, 4.0–6.0%), but a value of only 4.0% (reference value, 4.8–5.9%) was found with a turbidimetric immunoassay. Haematological analysis revealed a mild anaemia but other parameters were within the normal range. Hb-HPLC analysis demonstrated an unknown Hb variant (47.0%) separating from HbA (46.7%), but capillary electrophoresis identified no abnormal peaks. Mutation analysis identified the Hb Raleigh ( β1[NA1]Val → Ala [G TG → G CG]) mutation in combination with an α+-thalassaemia, a hitherto undescribed association. The Hb Raleigh mutation could be detected by PCR–RFLP or a multiplex allele-specific PCR assay.

Conclusions

Hb Raleigh can cause falsely increased HbA1c values on cation-exchange HPLC. Definitive diagnosis of this variant using combined Hb and DNA analyses is therefore essential.
Causes of discordance between thyroglobulin antibody assays
Authors: Pickett Alan John , Jones Meinir , Evans Carol
Published: July 2012

Background

Anti-thyroglobulin (Anti-Tg) assays show poor concordance.

Methods

We have investigated concordance and the causes of discordance between Abbott, Roche and Immulite Anti-Tg assays in 606 patients followed up for differentiated thyroid cancer (DTC). The reference range (RR) or lower reporting limit (LRL) was used to classify samples as negative or positive.

Results

Anti-Tg prevalence ranged between 6% and 55% depending on the method and cut-off. Concordance was 45% using LRL and 75% using RR. Specimens between the RR and LRL using the Immulite and Roche assays were identified that were positive by the Abbott assay and showed poor recovery of Tg in the Tg assay. This suggests misclassification using the RR. Anti-Tg International Reference Preparation (IRP) concentrations measured by the Roche and Abbott methods agreed well but patient samples did not. This is likely to be due to the heterogeneity of Anti-Tg. The Immulite assay appeared less sensitive than the Abbott and Roche based on investigations using the IRP and the low prevalence of Anti-Tg in the DTC patients (6–8%). Interference by Tg (>1000 μg/L) in the Roche assay was also identified as a cause of assay discordance.

Conclusions

Anti-Tg is used as a tumour marker for DTC and to predict interference in Tg assays themselves and hence inform clinicians of reported Tg concentrations. We have identified several causes of Anti-Tg assay discordance. This includes variation in assay sensitivity and interference from Tg, the heterogeneity of Anti-Tg and the use of different cut-offs to classify samples as antibody-positive or -negative.
The ‘family–work project’: children’s and parents’ experiences of working parenthood
Authors: Harden Jeni , MacLean Alice , Backett-Milburn Kathryn , Cunningham-Burley Sarah
Published: July 2012

In the United Kingdom, 83% of families have at least one parent engaged in some form of paid employment. However, the ambiguity within the moral expectations of working parenthood is experienced by some parents as a tension between competing demands for their time. Despite children being considered to be active family members, their views are often absent from research findings. This article draws on data from a qualitative, longitudinal study with 14 working families from Scotland and focuses on children’s and parents’ experiences of working parenthood over time, and how these experiences can be understood in relation to the moral narratives of parenting and constructions of childhood.
Assessing Pharmacy Residents' Knowledge of Biostatistics and Research Study Design
Authors: Bookstaver P Brandon , Miller April D , Felder Tisha M , Tice Danielle L , Norris LeAnn B , Sutton S Scott
Published: July 2012

BACKGROUND:

Historically, clinicians have demonstrated a lack of confidence and poor aptitude for biostatistics as a tool for medical literature interpretation. Evaluation of pharmacy residents' ability to interpret biostatistics commonly used in peer-reviewed literature has not been previously conducted.

OBJECTIVE:

To evaluate the level of understanding and perception of biostatistics concepts among pharmacy residents.

METHODS:

A survey of postgraduate year 1 (PGY1) residents in American Society of Health-System Pharmacists–accredited residency programs was conducted in May 2009. The survey instrument consisted of 27 items, including 10 knowledge-based questions, and was distributed to residency programs for anonymous reporting via SurveyMonkey. The primary outcome of interest was biostatistics knowledge, defined as the percent total score of correct knowledge items. Statistical attitude and confidence questions were rated on a 5-point Likert-type scale (1 = strongly disagree, 5 = strongly agree). The t-test or 1-way analysis of variance was conducted, as appropriate, to assess for differences in mean biostatistics knowledge scores by respondent characteristics. Forward stepwise regression was used to identify which characteristics were independently associated with biostatistics knowledge.

RESULTS:

A total of 214 PGY1 residents responded to the online survey assessment, and a subset of respondents (n = 166) answered 1 or more of the biostatistics knowledge questions. Of those who responded to at least 1 knowledge assessment, the overall mean (SD) biostatistics knowledge score was 47.3% (18.50%; range 0-90). Overall, respondents were predominantly female (74%) and younger than 30 years (81%). Residents scored highest in the recognition of the purpose of a double-blind study (92.6%; 95% CI 88.52 to 96.67), interpretation of relative risk (75.8%; 95% CI 69.02 to 82.57), and identification of the appropriate analytic method for a nominal variable (69.4%; 95% CI 62.16 to 76.59). Bivariate analyses showed that there were statistically significant mean differences in knowledge scores by attitude (p = 0.001) and confidence (p < 0.001). The multivariate model showed that above-average confidence ratings were associated with an absolute increase of 7.6% in biostatistics knowledge score (p < 0.019) compared to those whose confidence rating was at or below average.

CONCLUSIONS:

Overall, pharmacy residents' perception and understanding of biostatistics were poor in this assessment, which correlates with previous reports. Enhanced training in biostatistics and literature evaluation of both mentors and trainees should be incorporated in PharmD programs and residency training sites.
Retrospective Evaluation of Enoxaparin Dosing in Patients 48 Weeks' Postmenstrual Age or Younger in a Neonatal Intensive Care Unit
Authors: Hicks J Kevin , Shelton Chasity M , Sahni Jasmine K , Christensen Michael L
Published: July 2012

BACKGROUND:

Enoxaparin is the anticoagulant of choice in neonates because of the ease of administration, predictable pharmacokinetics, and reduced adverse effects when compared to heparin. The Chest guidelines recommend that therapy in patients younger than 2 months should be initiated with enoxaparin 1.5 mg/kg administered subcutaneously twice daily. This starting dosage may be inadequate, leading to a delay in achieving therapeutic anti-factor Xa plasma concentrations.

OBJECTIVE:

To determine an enoxaparin dose for neonatal patients that achieves a therapeutic anti-factor Xa plasma concentration and compare that dose to the recommended enoxaparin dose per published guidelines for this patient population.

METHODS:

The study was designed as a single-center chart review. Eligible patients were identified by pharmacy anticoagulation records or a search of the electronic medical record for enoxaparin orders. Patients must have received enoxaparin subcutaneously twice daily and have had a postmenstrual age of 48 weeks or younger. Patients diagnosed with renal failure and those receiving prophylactic doses of enoxaparin were excluded.

RESULTS:

The mean (SD) initial dose of enoxaparin was 1.4 (0.3) mg/kg subcutaneously twice daily, resulting in 27 of 33 patients (81.8%) having a subtherapeutic anti-factor Xa concentration. A mean enoxaparin dose of 2.0 (0.5) mg/kg was required to achieve a therapeutic anti-factor Xa plasma concentration (p < 0.001). Patients born prematurely required a higher enoxaparin dose (2.2 [0.5] mg/kg) than did those born at full-term gestation (1.8 [0.4] mg/kg; p < 0.05).

CONCLUSIONS:

For patients 48 weeks' postmenstrual age or younger who are treated in a neonatal intensive care unit, a higher initial dose of enoxaparin than that suggested by the Chest guidelines is required to attain a therapeutic anti-factor Xa plasma concentration. Premature neonates require a larger starting dose of enoxaparin than do infants born at full-term gestation.
Ranolazine-Induced Severe Bladder Hypotonia
Authors: Panfili Marco , Iafrate Massimo , Marzot Filippo , Secco Silvia , De Rosa Giovanni , Groppa Francesca , Padrini Roberto
Published: July 2012

OBJECTIVE:

To describe a case of acute urinary retention due to bladder hypotonia during ranolazine treatment.

CASE SUMMARY:

An 81-year-old male with multiple cardiovascular diseases was hospitalized for worsening angina and heart failure symptoms. Ranolazine 375 mg twice daily was started, in addition to ongoing therapy (clopidogrel 75 mg once daily, diltiazem 60 mg 3 times daily, isosorbide mononitrate 40 mg 3 times daily, carvedilol 6.25 mg twice daily, rosuvastatin 20 mg once daily, enoxaparin 5000 IU once daily, pentoxifylline 600 mg twice daily, pantoprazole 40 mg twice daily, enalapril 20 mg twice daily, furosemide 150 mg once daily, and spironolactone 37 mg once daily). Two months later, the ranolazine dose was increased to 500 mg twice daily; shortly thereafter, acute urinary retention occurred and persisted despite institution of α-lytic (alfuzosin) and antiandrogenic (dutasteride) therapy. A urodynamic study revealed that urinary retention was caused by severe hypocontractility of the detrusor muscle. Ranolazine was withdrawn and, within 2 days, the patient recovered his ability to void spontaneously; a second urodynamic study confirmed that detrusor contractility was substantially improved. Drug rechallenge was not performed due to the patient's clinical condition. Nevertheless, a phenotyping test to assess the activity of the cytochrome isoenzymes CYP3A4 and CYP2D6 (responsible for ranolazine metabolism) was performed, with dextromethorphan used as the probe drug. The urinary metabolic ratios indicated relatively low activity for CYP3A4 and intermediate activity for CYP2D6.

DISCUSSION:

The causal role of ranolazine in our case of bladder hypotonia is probable according to the Naranjo criteria. The mechanism of bladder dysfunction is tentatively ascribed to blockage of late sodium current in smooth muscle cells. Although drug plasma concentrations were not measured, they were probably elevated, since the metabolic activity of CYP3A4 was at the lower end of the reference range. Enzyme inhibition produced by diltiazem may have contributed to decreasing CYP3A4 activity.

CONCLUSIONS:

Acute urinary retention in elderly men taking ranolazine may be due to drug-induced bladder hypotonia.
Penetration of Light into Multiple Scattering Media: Model Calculations and Reflectance Experiments. Part I: The Axial Transfer
Authors: Oelkrug Dieter , Brun Manfred , Rebner Karsten , Boldrini Barbara , Kessler Rudolf
Published: July 2012

The article presents two general equations of radiation penetration into layers of diffuse reflectors. One of the equations describes the depth origins of reflection, the other the depth profiles of absorption. The equations are evaluated within the theory of radiative transfer applying various degrees of analytical approximations and Monte Carlo simulations. The data are presented for different scattering and absorption coefficients, arbitrary layer thicknesses, collimated and diffused irradiation, and anisotropic forward scattering. The calculated mean depths of reflection are always lower than the mean depths of absorption. For nearly non-absorbing layers, the mean depths of absorption are about one third of the physical layer thickness. In contrast, penetration saturates for strong absorbers at very low depth levels. From the simulated data, methods are derived for the determination of the penetration depth from reflectance and transmittance data of thin layers or from radially diffused reflectance profiles upon spot irradiation. The methods are experimentally verified for a series of metal oxide powders with particle sizes ranging from much smaller to much larger than the wavelength of irradiation and for microcrystalline cellulose stained with different concentrations of an organic dye.
Early Diagnosis of Prostate Cancer by Citrate Determination in Urine with Europium–Oxytetracycline Complex
Authors: Silva Flávia R. O. , Nabeshima Camila T. , Bellini H. , Courrol Lilia C.
Published: July 2012

Normal prostate tissue contains high levels of citrate. In the presence of prostate cancer, the citrate level is diminished. In this paper we show that it is possible to use europium–oxytetracycline complex as a citrate fluorescent probe and consequently as a prostate cancer probe. We analyzed normal nude male mice urine and urine from nude male mice in which prostate cancer was induced by intraprostatic inoculation of DU145 cells. The urine samples were collected from the animals at the 7th, 14th, 21st, and 35th days after the surgery procedures. The intensity of europium emission at 615 nm in europium–oxytetracycline complex in the presence of citrate increases linearly. The citrate concentrations were determined from a calculated calibration curve. A concentration decrease in malignant prostate urine from the normal (PBS group) urine value from ∼8.0 mM to ∼2.4 mM (tumor group at 35th day) was found. The obtained results indicated that europium–oxytetracycline provides a significant biomarker for prostate cancer detection with a direct, accurate, noninvasive, and non-enzymatic method for measurement of citrate in biological fluids.
Integration of an Intensified Charge-Coupled Device (ICCD) Camera for Accurate Spectroscopic Measurements
Authors: Peláez Ramón Javier , Mar Santiago , Aparicio Juan Antonio , Belmonte María Teresa
Published: July 2012

Intensified charge-coupled devices (ICCD) are used in a great variety of spectroscopic applications, some of them requiring high sensitivity and spectral resolution. The setup, configuration, and featuring of these cameras are fundamental issues in order to acquire high quality spectra. In this work a critical assessment of these detectors is performed and the specific configuration, the optical alignment, featuring, and the dark and shot noise are described and analyzed. Spatial response of the detector usually shows a significant lack of spatial homogeneity and a map of interferences may appear in certain ranges of wavelengths, which damages the quality of the recorded spectra. In this work the spectral resolution and the spatial and spectral sensitivity are also studied. The analysis of the dark current reveals the existence of a smooth but clear spatial dependence. As a final conclusion, the spectra registered with the spectrometer equipped with our ICCD camera allow us to explore and measure accurately spectral line shapes emitted by pulsed plasmas in the visible range and particularly in the ultraviolet (UV) range.
Inductively Coupled Plasma–Mass Spectrometry (ICP-MS) for Quantitative Analysis in Environmental and Life Sciences: A Review of Challenges, Solutions, and Trends
Authors: Pröfrock Daniel , Prange Andreas
Published: July 2012

This focal point review provides an overview of recent developments and capabilities of inductively coupled plasma mass spectrometry (ICPMS) coupled with different separation techniques for applications in the fields of quantitative environmental and bio-analysis. Over the past years numerous technical improvements, which are highlighted in this review, have helped to promote the evolution of ICP-MS to one of the most versatile tools for elemental quantification. In particular, the benefits and possibilities of using state-of-the-art hyphenated ICP-MS approaches for quantitative analysis are demonstrated with a focus on environmental and bio-analytical applications.
Unresolved Discrepancies between Cannabinoid Test Results for Infant Urine
Authors: Barakauskas Vilte E , Davis Rebecka , Krasowski Matthew D , McMillin Gwendolyn A
Published: July 2012

BACKGROUND

False-positive drug screen results for tetrahydrocannabinol (THC) have been observed. This study investigated the rate of unconfirmed positive screen results in infant and noninfant urine samples and evaluated possible reasons for differences.

METHODS

The rate of unconfirmed positive THC screen results for urine samples was determined retrospectively in 2 independent data sets (n = 14 859, reference laboratory; n = 21 807, hospital laboratory) by comparing positive immunoassay-based drug screen results with the associated results of confirmation tests. We then assessed the rate of positive THC screens for samples with varying likelihoods of cannabinoid presence to evaluate the contribution of infant-specific urine constituents to positive results. Finally, a method to detect a THC metabolite (11-hydroxy-Δ9-THC) that occurs in meconium was developed to determine its prevalence in infant urine.

RESULTS

Positive screen results failed to confirm more frequently in samples from infants (47%) than in noninfants (0.8%). The hospital laboratory observed a similar discrepancy with a different immunoassay. Infant samples with a high likelihood of containing cannabinoids despite negative confirmatory results had a similar rate of positive screening results (50%, n = 20), whereas all samples with a low likelihood of containing cannabinoids screened negative (n = 23). 11-Hydroxy-Δ9-THC was not detected in any infant urine sample tested (n = 16).

CONCLUSIONS

Conventional confirmatory methods for THC may be inappropriate for urine samples from infants. Our results suggest that one or more currently unrecognized THC-associated compounds are responsible for positive THC screen results for infant urine, as opposed to an infant-associated interference.
Salvaging the records of salvage ethnography: The story of the Digital Himalaya Project
Authors: TURIN MARK
Published: July 2012

The Digital Himalaya Project is a collection, storage and dissemination portal for scholarly content and research findings about the Himalayan region. The project website connects a worldwide user community to a vast corpus of digital resources from or about India, Nepal, Bhutan and
the Tibetan plateau for free and easy download - without payment, subscription or password.

While Digital Himalaya began as a strategy for collecting and protecting the products of colonial-era ethnographic collections on the Himalayas - for posterity and for access by source communities
- the project has now become a collaborative digital publishing environment, bringing a new collection online every month, with close to half a million web visitors since its establishment in 2000.

Almost all of our digitization and scanning is now conducted in Nepal, dramatically reducing
operating costs and increasing productivity. Our funding no longer comes from research councils in the United Kingdom and the United States, but through web referrals and from individual or institutional donations around the world. The project is now supported by people and organizations that
recognize the work and want to contribute to it.

In short, what began as an academic research project a decade ago is now a vast online portal for hosting and disseminating knowledge about the Himalayas to a demanding, fast-growing and truly global user base.
history.child.book.shop.2.0.
Authors: PAUL LISSA
Published: July 2012

In the context of the 2011 London riots and the 'Occupy Wall Street' protests, I question what it means to be literate by contrasting communication strategies (used effectively by social networking young people to provoke social change), against banal official forms of literacy (defined
by large scale state-mandated curriculum and assessment exercises) as used to close it down. By focusing on ways in which twenty-first century constructions of 'history' 'child' 'book' and 'shop' are pre-figured by the late-Enlightenment constructions of those terms, I explain that an eighteenth
revolutionary ethos (formed largely in the aftermaths of the French and American revolutions) can be used as a precedent for an emerging twenty-first century ethos – which although revolutionary, is as yet undefined. To demonstrate how late-Enlightenment constructions of my four key
terms, history, child, book and shop, prefigure their twenty-first century '2.0' counterparts, I locate my discussion in the children's book businesses of each period. Taking my cue from Marshall McLuhan's prescient aphorism, 'we march backwards into the future', I show how education is used,
as he says, 'as an instrument of cultural aggression, imposing upon retribalized youth the obsolescent visual values of the dying literate age'.
Improvisation and intimate technologies
Authors: Spain Kent De
Published: July 2012

This article investigates the concept and experience of intimacy in creative process, specifically through the complex interaction of human improvisation and digital technologies in performance situations. By looking first at conceptions of intimacy and then at reports by artists working
at the performance/technology interface, this article examines how working creatively against resistance can increase the sense of intimacy in the moment of performance. The article goes on to look, in detail, at how these concepts play out in two contemporary performance works: one by the
author and one by Dutch theatre artist Dries Verhoeven.
Objective and subjective analysis of women's voice with idiopathic Parkinson's disease
Authors: Graças Riviana Rodrigues das , Gama Ana Cristina Côrtes , Cardoso Francisco Eduardo Costa , Lopes Bárbara Pereira , Bassi Iara Barreto
Published: July 2012

OBJECTIVE: To compare the voice quality of women with idiopathic Parkinson's disease and those without it. METHODS: An evaluation was performed including 19 female patients diagnosed with idiopathic Parkinson's disease, with an average age of 66 years, and 27 women with an average of 67 years-old in the Control Group. The assessment was performed by computed acoustic analysis and perceptual evaluation. RESULTS: Parkinson's disease patients presented moderate rough and unstable voice quality. The parameters of grade, roughness, and instability had higher scores in Parkinson's disease patients with statistically significant differences. Acoustic measures of Jitter and period perturbation quotient (PPQ) significantly differ between groups. CONCLUSIONS: Parkinson's disease female individuals showed more vocal alterations compared to the Control Group, when both perceptual and acoustic evaluations were analyzed.
Reliability and validity study of a Brazilian-Portuguese version of the fatigue severity scale in Parkinson's disease patients
Authors: Valderramas Silvia , Feres Ana Cristina , Melo Ailton
Published: July 2012

The Fatigue Severity Scale (FSS) is one of the most frequently used self-rating scales for fatigue in Parkinson's disease (PD) and it lacks a validated Brazilian-Portuguese version. OBJECTIVE: To determine the construct validity and reproducibility of a Brazilian-Portuguese version of the FSS in patients with PD. METHODS: In a cross-sectional study, a Portuguese-language version of the FSS was applied to 30 patients with PD (62±11 years-old). The Parkinson's disease questionnaire (PDQ-39) was used as the validation criterion, while the Hoehn and Yahr scale, the Unified Parkinson's Disease Rating Scale (UPDRS), and the Beck Depression Inventory were employed to analyze the correlations with the FSS score. RESULTS: The test-retest intraclass correlation coefficient was 0.91 (p<0.01) for the Brazilian-Portuguese version of the FSS score, which was highly correlated with the PDQ-39 overall score (r=0.93; p<0.01) and the Beck Depression Inventory (r=0.75; p<0.01). It showed a correlation with the Hoehn and Yahr scale (r=0.40; p=0.02), and with the UPDRS as well (r=0.45, p=0.01). CONCLUSIONS: The Brazilian-Portuguese version of the FSS is valid and reproducible for using in Brazilian patients with PD.