bluuebunny/crossref_metadata_2025 huggingface dataset:
Section Preequating Under the Equivalent Groups Design Without IRT
Authors: Guo Hongwen , Puhan Gautam
Published: August 2014

In this article, we introduce a section preequating (SPE) method (linear and nonlinear) under the randomly equivalent groups design. In this equating design, sections of Test X (a future new form) and another existing Test Y (an old form already on scale) are administered. The sections of Test X are equated to Test Y, after adjusting for the imperfect correlation between sections of Test X, to obtain the equated score on the complete form of X. Simulations and a real‐data application show that the proposed SPE method is fairly simple and accurate.
The effects of bisphosphonate zoledronic acid in hepatocellular carcinoma, depending on mevalonate pathway
Authors: Honda Yohji , Takahashi Shoichi , Zhang Yizhou , Ono Atsushi , Murakami Eisuke , Shi Niu , Kawaoka Tomokazu , Miki Daiki , Tsuge Masataka , Hiraga Nobuhiko , Abe Hiromi , Ochi Hidenori , Imamura Michio , Aikata Hiroshi , Chayama Kazuaki
Published: August 2014

Background and Aim

Zoledronic acid (ZOL) is a nitrogen‐containing bisphosphonate and is used to reduce cancer‐induced osteolysis. We reported previously that ZOL delayed both the growth and pain progression of bone metastases from hepatocellular carcinoma. The present study was designed to evaluate the effects of ZOL on hepatoma cell lines and the molecular mechanisms of such effects.

Methods

Cell viability assay, scratch assay, immunohistochemistry, Western blotting, and flow cytometry analysis were performed using Huh7 and HepG2 cells treated with and without ZOL.

Results

ZOL reduced cell growth in a dose‐dependent manner and prevented cell migration when used at a concentration exceeding 10 μM. Immunohistochemistry showed that the inhibitory effects of ZOL on hepatoma cell progression was not due to the suppression of Ras and RhoA expression but due to inhibition of their translocation from the cytosol to the cell membrane, which terminates mevalonate pathway. Immunoblotting and flow cytometry showed that ZOL inhibited the mitogen‐activated protein kinase pathway (MAPK) and induced apoptosis of hepatoma cells.

Conclusions

Our results indicated that ZOL prevented cell growth and metastasis based on direct antitumor effects in hepatoma cells. The use of ZOL could not only suppress the progression to bone metastatic lesions but also prevented growth of primary hepatocellular carcinoma.
Suppression of oxidative stress and improvement of liver functions in mice by ursolic acid via LKB1‐AMP‐activated protein kinase signaling
Authors: Yang Yongbin , Zhao Zhanxue , Liu Yuanjun , Kang Xianjiang , Zhang Haisong , Meng Ming
Published: August 2014

Background and Aim

Hepatic cirrhosis is the final stage of liver dysfunction, characterized by diffuse fibrosis, which is the main response to the liver injury. This study is to investigate the effects of ursolic acid (UA) on liver functions and fibrosis in bile duct ligation (BDL) mice and to determine the underlying mechanisms.

Methods

Cultured hepatocytes were treated with lipopolysaccharide (LPS) in the presence or absence of UA. The reactive oxygen species (ROS) level, protein levels of IκBα, iNOS and Cox‐2, and NF‐κB activation were detected, respectively. C57/BL6 and AMP‐activated protein kinase (AMPK)α2–/– mice were subjected to BDL for 14 days. UA was administered by gavage. The markers of liver function and oxidative stress, and liver histopathology were analyzed after treatment.

Results

Treatment of hepatocytes with UA dose‐dependently activates AMPK, which is abolished by silence of liver kinase B1 (LKB1). LPS significantly increased ROS productions, apoptosis, NF‐κB activation, and expressions of iNOS and Cox‐2 in cultured hepatocytes. All these effects were blocked by co‐incubation with UA. Importantly, silence of LKB1, AMPK, or iNOS/Cox‐2 by small interference RNA transfection reversed UA‐induced effects in cultured cells. In an animal study, 14‐day BDL induced liver fibrosis and liver injury, accompanied with increased oxidative stress and protein expressions of iNOS and Cox‐2 in liver. Treatment of UA significantly attenuated the BDL‐induced detrimental effects in wild‐type mice but not in AMPKα2–/– mice.

Conclusion

UA via LKB1‐AMPK signaling offers protective effects on BDL‐induced liver injury in mice, which may be related to inhibition of oxidative stress.
Microdissection approaches in tuberculosis research
Authors: Hudock Teresa A. , Lackner Andrew A. , Kaushal Deepak
Published: August 2014

Mycobacterium tuberculosis, a globally significant pathogen, results in active or latent tuberculosis. The granuloma is the characteristic lesion that offers insight into host–pathogen interactions in these distinct states. Microdissection provides a way to isolate and consequently investigate specific tissue sections. We review various techniques available and in use.
Analysis of the efficacy of three treatment options for cesarean scar pregnancy management
Authors: Li Yue‐ran , Xiao Song‐shu , Wan Ya‐jun , Xue Min
Published: August 2014

Aim

To assess three different methods in treating patients with cesarean scar pregnancy (CSP).

Methods

We evaluated pre‐, intra‐ and postoperative conditions of 124 CSP patients in one of the three treatment groups, of which 37 patients underwent uterine curettage by hysteroscopy under ultrasound monitoring (group 1), 28 patients were treated with methotrexate followed by hysteroscopy (group 2) and 59 cases underwent uterine arterial embolization followed by hysteroscopy (group 3). The treatment options were determined based on the patients' conditions.

Results

Among all three groups, group 3 (uterine arterial embolization followed by hysteroscopy) had the least intraoperative blood loss and the highest success rate with curettage, but the highest hospitalization cost. Group 1 (only hysteroscopy) had the shortest length of hospitalization and the lowest cost, but the highest intraoperative blood loss and slowest recovery. Group 2 (methotrexate followed by hysteroscopy) had the longest period of hospitalization, and other indexes had fallen in between the other two groups.

Conclusion

Among the three methods, uterine arterial embolization followed by hysteroscopy is the safest and most efficient method without considering the cost of hospitalization. Patients with a low level of β‐hCG may consider choosing hysteroscopy under ultrasound monitoring or methotrexate followed by hysteroscopy. The advantage is low cost of hospitalization; however, patients may be under relatively higher surgical risks and lower first time surgical success rate, especially for patients treated by hysteroscopy under ultrasound monitoring.
Liver dysfunction in triplet pregnancies: Relation to antenatal changes in antithrombin activity and platelet count
Authors: Nishida Ryutaro , Morikawa Mamoru , Yamada Takahiro , Akaishi Rina , Yamada Takashi , Minakami Hisanori
Published: August 2014

Aim

The aim of this study was to determine whether antenatal decline in antithrombin (AT) activity occurs frequently and precedes the development of perinatal liver dysfunction in women with triplet pregnancies.

Material and Methods

A retrospective observational study was conducted on all women who gave birth to triplets at gestational week ≥22 at a single centre during a study period from January 2001 to March 2013. The following eight blood parameters were monitored weekly during the last 5 weeks of pregnancy and postpartum: AT activity, platelet count, fibrinogen, D‐dimer, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), uric acid and creatinine. Pregnancy‐induced AT deficiency (PIATD) and gestational thrombocytopenia were defined as antenatal AT activity <70% of normal level and antenatal platelet count <150 × 109/L, respectively. Liver dysfunction was defined as AST > 40 IU/L. LDH elevation was defined as LDH > 450 IU/L.

Results

Sixteen women were eligible for this study. All variables except LDH exhibited significant changes antenatally: AT activity, platelet count and fibrinogen decreased, while D‐dimer, AST, urate and creatinine increased. LDH increased significantly postpartum. PIATD, gestational thrombocytopenia, perinatal liver dysfunction, and LDH elevation occurred in eight, seven, six, and eight women, respectively. Liver dysfunction was preceded by PIATD alone in three, by both PIATD and gestational thrombocytopenia in one and by gestational thrombocytopenia alone in none of the subjects. After delivery, laboratory abnormalities similar to HELLP syndrome were seen in three women exclusively in the presence of PIATD.

Conclusions

Reduced AT activity was likely to precede perinatal liver dysfunction in women with triplets.
Accuracy and cost‐analysis of placental alpha‐microglobulin‐1 test in the diagnosis of premature rupture of fetal membranes in resource‐limited community settings
Authors: Eleje George Uchenna , Ezugwu Euzebus Chinonye , Ogunyemi Dotun , Eleje Lydia Ijeoma , Ikechebelu Joseph Ifeanyichukwu , Igwegbe Anthony Osita , Okonkwo John E. , Ikpeze Okechukwu Christian , Udigwe Gerald Okanandu , Onah Hyacinth Eze , Nwosu Betrand Obi , Ezeama Chukwuemeka Okwudili , Ezenkwele Eziamaka Pauline
Published: August 2014

Aim

To determine accuracy and costs of placental α‐microglobulin‐1 (PAMG‐1) test compared to standard clinical assessment (SCA) for diagnosing rupture of membranes (ROM).

Methods

A multicenter double‐blind study of consecutive women with symptoms and signs of ROM in Nnamdi Azikiwe University Teaching Hospital, Nnewi and University of Nigeria Teaching Hospital, Enugu, both in south‐east Nigeria using SCA for ROM and the PAMG‐1 test was done. ROM was diagnosed if two out of three methods from SCA (pooling, positive nitrazine test or ferning) were present and confirmed post‐delivery based on presence of any two of these clinical criteria: delivery in 48 h to 7 days, evidence of chorioamnionitis, membranes overtly ruptured at delivery and adverse perinatal outcomes strongly correlated with prolonged PROM. A cost‐analysis was also done. The outcome measures included sensitivity, specificity, accuracy and costs for the two tests.

Results

Accuracy, sensitivity and specificity for the PAMG‐1 test were 97.2%, 97.4% and 96.7%, higher than for SCA which were 83.7%, 87.9% and 70.5%, respectively (P < 0.001). Accuracy of SCA was higher at less than 34 weeks than 34 weeks or more (88.3% vs 81.4%) while the PAMG‐1 test performed equally at both gestational age categories (96.1% vs 97.7%). In women without pooling, accuracy of the PAMG‐1 test was 96.7%, while it was 40.0% with SCA. Analysis showed that the overall cost of SCA was 45% higher than the PAMG‐1 test.

Conclusion

This study confirms that the PAMG‐1 test has a consistently high diagnostic accuracy at all gestational ages and with equivocal cases of ROM. The PAMG‐1 test appears less costly than SCA.
Hemodynamic effects of nifedipine tocolysis
Authors: Yamasato Kelly , Burlingame Janet , Kaneshiro Bliss
Published: August 2014

Aim

To describe the effects of nifedipine tocolysis on blood pressure and heart rate in non‐hypertensive women.

Methods

This was a retrospective study from 2001 to 2011 to compare blood pressures and heart rates among non‐hypertensive women on nifedipine tocolysis up to 8 h after nifedipine initiation. Measurements at 20–60 and 61–120 min were compared to assess the differential effects of dosing on hemodynamics and reflected the effects of the initial and complete loading doses, respectively. Charts were reviewed for hypotension‐related emergent delivery.

Results

One hundred and thirty‐eight patients were included. Over the 8‐h study interval, mean systolic blood pressure (P < 0.001) and mean diastolic blood pressure (P < 0.001) decreased by 5 mmHg and heart rate increased by 4 b.p.m. (P < 0.001). Systolic and diastolic blood pressures were unchanged from baseline up to 120 min at all doses. Heart rate increased at both 20–60 and 61–120 min when all doses were considered (P < 0.001), but differential dosing effects were not observed. Rates of tachycardia increased (P < 0.001), but rates of hypotension were unchanged. No hypotension‐related emergent deliveries occurred.

Conclusion

Nifedipine tocolysis was associated with hemodynamic changes in non‐hypertensive women. Tachycardia was increased but hypotension was unaffected, supporting the general safety of nifedipine in this setting.
Maternal outcomes in pregnancies affected by varicella zoster virus infections: Population‐based study on 7.7 million pregnancy admissions
Authors: Zhang Hui Jue , Patenaude Valerie , Abenhaim Haim A.
Published: August 2014

Aim

Previous estimates of the incidence of varicella zoster virus (VZV) pneumonia and maternal death associated with VZV infection among the pregnant population have varied considerably and been based predominantly on reports from case series. We sought to measure the incidence of VZV‐related morbidity and mortality to provide more representative population estimates.

Methods

We carried out a large cohort study on all births using the United States Healthcare Cost and Utilization Project‐Nationwide Inpatient Sample database between 2003 and 2010. Descriptive statistics were used to measure baseline characteristics and outcomes of women with VZV infection. Multivariate logistic regression analyses were used to identify risk factors for the development of VZV‐related morbidity and mortality.

Results

We identified 935 patients admitted for VZV infection among 7.7 million pregnancy admissions, representing an incidence of 1.21 cases/10 000 pregnancies (95% confidence interval [CI], 1.13–1.29). The incidence of VZV pneumonia was 2.5% (95% CI, 1.6–3.7). No maternal deaths were recorded during the 8‐year study period. There were no significant risk factors identified for those who developed VZV pneumonia compared to those who had an uncomplicated VZV infection during pregnancy.

Conclusion

The incidence of VZV pneumonia and VZV infection associated with maternal death is significantly lower than previously estimated and may reflect better immunization and earlier interventions.
Novel treatment of chronic perineal pain in a woman by extracorporeal shock wave therapy: A case report and published work review
Authors: Tung Chi Wai , Cheon Willy Cecilia , Tong Anny
Published: August 2014

In published work review, extracorporeal shock wave therapy (ESWT) has been showed to be effective in treating chronic perineal/pelvic pain in men, but there was no published report on its use in women. We report a case of female chronic perineal pain successfully treated by ESWT. A 51‐year‐old woman presented with persistent perineal scar pain after excision of a vulval–vaginal nodule despite oral analgesics and gabapentin. After 11 cycles of ESWT, she reported termination of analgesics consumption and decreased perineal pain score from 8 to 2. The Short Form 36 Questionnaire demonstrated improvement in physical and mental health conditions. There was no complication encountered. We postulate that the effect of ESWT in this patient was based on reduction of muscle tone and alternating the threshold of pain memory, similar to the mechanisms in male patients. Further study is required to determine the use of ESWT in treating female chronic perineal pain.
Case of non‐mosaic trisomy 20 in amniotic fluid cultures without anomalies in the fetus: Cytogenetic discrepancy between amniocytes and fetal blood
Authors: Maeda Kazuhisa , Imoto Issei , Kaji Takashi , Yoshida Yukiko , Nakayama Soichiro , Irahara Minoru
Published: August 2014

We report a case of non‐mosaic trisomy 20 detected prenatally by amniocentesis during the 16th week of pregnancy. Fetal blood sampling showed a normal karyotype and no fetal, neonatal or infant abnormalities were observed. Amniotic fluid cell karyotyping revealed a trisomy 20 (47,XY,+20) with 100% trisomic cells (38/38); however, a subsequent cordocentesis revealed a normal male karyotype. Moreover, a follow‐up ultrasonographic examination did not reveal any major congenital malformations, and a healthy male infant was delivered subsequently at an appropriate gestational age without obvious anomalies. Cytogenetic analysis of blood lymphocytes from the infant revealed a normal karyotype, but cultured cells from the term placenta showed a mosaic karyotype 47,XY,+20/46,XY with 88% trisomic cells (44 of 50). Furthermore, no anomalies or developmental delays were observed in the neonatal period, thus suggesting two possibilities: confined placental mosaicism with the presence of normal and abnormal cell lineages, or generalized mosaicism affecting a limited number of tissues in both the placenta and fetus.
Clinical features of gestational thrombocytopenia difficult to differentiate from immune thrombocytopenia diagnosed during pregnancy
Authors: Kasai Junko , Aoki Shigeru , Kamiya Natsuko , Hasegawa Yoshimi , Kurasawa Kentaro , Takahashi Tsuneo , Hirahara Fumiki
Published: August 2014

Aim

To investigate the clinical features of gestational thrombocytopenia (GT) difficult to differentiate from immune thrombocytopenia (ITP) during pregnancy.

Methods

The January 2000–December 2012 hospital database was analyzed to identify women with ITP or GT (after excluding other possible causes of thrombocytopenia) among those first noted to have platelet counts of less than 100 000/μL during pregnancy. The maternal characteristics, platelet count fluctuations and pregnancy outcomes were compared between women with ITP and GT.

Results

There were 23 pregnancies (22 women) with thrombocytopenia (GT, 13; ITP, 10). The GT group included five twin pregnancies (38.5%), whereas all pregnancies of the ITP group were singleton pregnancies, with significantly more twin pregnancies in the GT group (P = 0.046). Thrombocytopenia in the first trimester occurred in 70% (7/10) of ITP cases and 23.1% (3/13) of even GT cases. The nadir platelet count was less than 70 000/μL in 100% (10/10) of ITP cases and 30.8% (4/13) of GT cases (P < 0.001). Maternal treatment was required in 80% (8/10) of ITP cases, but in none of the GT cases. The pregnancy outcomes were favorable in both groups, and no case required fetal treatment.

Conclusion

Gestational thrombocytopenia with platelet counts of less than 10 0000/μL occurred more frequently in twin pregnancies. Although onset of thrombocytopenia in the first trimester and a platelet count of less than 70 000/μL is more common in ITP, these findings were not uncommon in GT. Differentiation between ITP and GT may be feasible only with post‐partum changes in the platelet count.
STABILITY OF THE EXPONENTIAL UTILITY MAXIMIZATION PROBLEM WITH RESPECT TO PREFERENCES
Authors: Xing Hao
Published: August 2014

This paper studies stability of the exponential utility maximization when there are small variations on agent's utility function. Two settings are considered. First, in a general semimartingale model where random endowments are present, a sequence of utilities defined on converges to the exponential utility. Under a uniform condition on their marginal utilities, convergence of value functions, optimal payoffs, and optimal investment strategies are obtained, their rate of convergence is also determined. Stability of utility‐based pricing is studied as an application. Second, a sequence of utilities defined on converges to the exponential utility after shifting and scaling. Their associated optimal strategies, after appropriate scaling, converge to the optimal strategy for the exponential hedging problem. This complements Theorem 3.2 in [Nutz, M. (2012): Risk aversion asymptotics for power utility maximization. Probab. Theory & Relat. Fields 152, 703–749], which establishes the convergence for a sequence of power utilities.
Identification of molecular mechanisms used by Finegoldia magna to penetrate and colonize human skin
Authors: Murphy Elizabeth C. , Mörgelin Matthias , Reinhardt Dieter P. , Olin Anders I. , Björck Lars , Frick Inga‐Maria
Published: August 2014

Finegoldia magna is a Gram‐positive anaerobic commensal of the human skin microbiota, but also known to act as an opportunistic pathogen. Two primary virulence factors of F. magna are the subtilisin‐like extracellular serine protease SufA and the adhesive protein FAF. This study examines the molecular mechanisms F. magna uses when colonizing or establishing an infection in the skin. FAF was found to be essential in the initial adherence of F. magna to human skin biopsies. In the upper layers of the epidermis FAF mediates adhesion through binding to galectin‐7 – a keratinocyte cell marker. Once the bacteria moved deeper into the skin to the basement membrane layer, SufA was found to degrade collagen IV which forms the backbone structure of the basement membrane. It also degraded collagen V, whereby F. magna could reach deeper dermal tissue sites. In the dermis, FAF interacts with collagen V and fibrillin, which presumably helps the bacteria to establish infection in this area. The findings of this study paint a clear picture of how F. magna interacts with human skin and explain how it is such a successful opportunistic pathogen in chronic wounds and ulcers.
Litter elemental stoichiometry and biomass densities of forest soil invertebrates
Authors: Ott David , Digel Christoph , Klarner Bernhard , Maraun Mark , Pollierer Melanie , Rall Björn C. , Scheu Stefan , Seelig Gesine , Brose Ulrich
Published: August 2014

To maintain constant chemical composition, i.e. elemental homeostasis, organisms have to consume resources of sufficient quality to meet their own specific stoichiometric demand. Therefore, concentrations of elements indicate resource quality, and rare elements in the environment may act as limiting factors for individual organisms scaling up to constrain population densities. We investigated how the biomass densities of invertebrate populations of temperate forest soil communities depend on 1) the stoichiometry of the basal litter according to ecological stoichiometry concepts and 2) the population average body mass as predicted by metabolic theory. We used a large data set on biomass densities of 4959 populations across 48 forests in three regions of Germany. Following various ecological stoichiometry hypotheses, we tested for effects of the carbon‐to‐element ratios of 10 elements. Additionally, we included the abiotic litter characteristics habitat size (represented by litter depth), litter diversity and pH, as well as forest type as an indicator for human management. Across 12 species groups, we found that the biomass densities scaled significantly with population‐averaged body masses thus supporting metabolic theory. Additionally, 10 of these allometric scaling relationships exhibited interactions with stoichiometric and abiotic co‐variables. The four most frequent co‐variables were 1) forest type, 2) the carbon‐to‐phosphorus ratio (C:P), 3) the carbon‐to‐sodium ratio (C:Na), and the carbon‐to‐nitrogen ratio (C:N). Hence, our analyses support the sodium shortage hypothesis for microbi‐detritivores, the structural elements hypothesis for some predator groups (concerning N), and the secondary productivity hypothesis (concerning P) across all trophic groups in our data. In contrast, the ecosystem size hypothesis was only supported for some meso‐ and macrofauna detritivores. Our study is thus providing a comprehensive analysis how the elemental stoichiometry of the litter as the basal resource constrain population densities across multiple trophic levels of soil communities.
BROKEN ‘TWO‐WAY WINDOWS’? AN EXPLORATION OF PROFESSIONAL HYBRIDS
Authors: CROFT CHARLOTTE , CURRIE GRAEME , LOCKETT ANDY
Published: August 2014

Professional hybrids are situated between managerial and professional groups, potentially enabling them to move between different organizational groups. Extant research assumes that professional hybrids undergo identity transition to overcome the conflicts associated with influencing two distinct organizational realms. However, how these identity conflicts are managed remains unclear. To explore how professional hybrids manage such identity conflicts we consider the experience of nurse hybrids. Drawing on the concept of liminality we argue that influence across multiple groups relies on the construction of a positive liminal space. In contrast, we demonstrate how nurse hybrids occupy a perverse liminal space, perpetuating identity conflict, preventing identity transition, and undermining their effectiveness as hybrids. Our work calls into question the reliance on professional hybrids as an organizational panacea for reform and develops our understanding of individual hybrids.
Sources of perceived social support associated with reduced psychological distress at 1 year after the Great East Japan Earthquake: Nationwide cross‐sectional survey in 2012
Authors: Sugimoto Takashi , Umeda Maki , Shinozaki Tomohiro , Naruse Takashi , Miyamoto Yuki
Published: August 2014

Aim

Lack of social support has been associated with a higher level of psychological distress after disasters, but its relative associations with sources of support such as neighbors, friends, family, and others, are underreported. The present study assessed the associations of social support with psychological distress according to support source among the general population 1 year after the Great East Japan Earthquake.

Methods

An online survey was completed by a Japanese national sample of 10 469 participants in 2012, from which 8777 were analyzed. Psychological distress was measured using the Kessler Psychological Distress Scale (K6), and the associations between social support from family, friends, or neighbors and psychological distress score were estimated using a proportional odds model. This model was separately fitted for house‐damage certification from the disaster (573 participants were certified, 8204 were uncertified).

Results

Prevalence of K6 ≥ 13 points was 8.4% for house‐damage certified and 9.0% for uncertified participants. K6 ≥ 5 points was observed among 49.9% of the house‐damaged certified group and in 47.7% of the uncertified group. Lack of support from family, friends, and neighbors was similarly associated with higher K6 score among house‐damage certified and uncertified participants. Similar patterns were observed from participants who received house‐damage certificates and those who did not experience damage to their homes.

Conclusion

Enhancing perceived sources of social support among the general population, not limited to people with house damage, can be an effective way to reduce psychological distress following a disaster.
Sealing future geographies: religious prophecy and the case of Joanna Southcott
Authors: Holloway Julian
Published: August 2014

This paper seeks to contribute to an emerging debate in human geography concerning the spatialities of the future, and aims to address a gap in work on the geography of religion regarding the temporalities of faith. Through a focus on religious prophecy, the paper seeks to examine how different spaces, temporalities, identities, practices and dispositions (both religious and secular‐scientific) are generated through and generate this religious future. The paper argues that prophecy is a particular form of making the future, and advances the dual notions cosmic‐divine time and preparatory assured readiness in order to understand and underline this specificity. Through the example of the prophetess Joanna Southcott (1750–1814) and an event involving a box of her prophecies publically opened in 1927, it argues that prophetic space‐times presence the future through multiple and intersecting ‘not‐yets’, hesitancies and assurances.
Evaluation of radiation dose and image quality of CT scan for whole‐body pediatric PET/CT: A phantom study
Authors: Yang Ching‐Ching , Liu Shu‐Hsin , Mok Greta S. P. , Wu Tung‐Hsin
Published: August 2014

Purpose:

This study aimed to tailor the CT imaging protocols for pediatric patients undergoing whole‐body PET/CT examinations with appropriate attention to radiation exposure while maintaining adequate image quality for anatomic delineation of PET findings and attenuation correction of PET emission data.

Methods:

The measurements were made by using three anthropomorphic phantoms representative of 1‐, 5‐, and 10‐year‐old children with tube voltages of 80, 100, and 120 kVp, tube currents of 10, 40, 80, and 120 mA, and exposure time of 0.5 s at 1.75:1 pitch. Radiation dose estimates were derived from the dose‐length product and were used to calculate risk estimates for radiation‐induced cancer. The influence of image noise on image contrast and attenuation map for CT scans were evaluated based on Pearsonˈs correlation coefficient and covariance, respectively. Multiple linear regression methods were used to investigate the effects of patient age, tube voltage, and tube current on radiation‐induced cancer risk and image noise for CT scans.

Results:

The effective dose obtained using three anthropomorphic phantoms and 12 combinations of kVp and mA ranged from 0.09 to 4.08 mSv. Based on our results, CT scans acquired with 80 kVp/60 mA, 80 kVp/80 mA, and 100 kVp/60 mA could be performed on 1‐, 5‐, and 10‐year‐old children, respectively, to minimize cancer risk due to CT scans while maintaining the accuracy of attenuation map and CT image contrast. The effective doses of the proposed protocols for 1‐, 5‐ and 10‐year‐old children were 0.65, 0.86, and 1.065 mSv, respectively.

Conclusions:

Low‐dose pediatric CT protocols were proposed to balance the tradeoff between radiation‐induced cancer risk and image quality for patients ranging in age from 1 to 10 years old undergoing whole‐body PET/CT examinations.
Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication
Authors: Carneiro Miguel , Rubin Carl-Johan , Di Palma Federica , Albert Frank W. , Alföldi Jessica , Barrio Alvaro Martinez , Pielberg Gerli , Rafati Nima , Sayyab Shumaila , Turner-Maier Jason , Younis Shady , Afonso Sandra , Aken Bronwen , Alves Joel M. , Barrell Daniel , Bolet Gerard , Boucher Samuel , Burbano Hernán A. , Campos Rita , Chang Jean L. , Duranthon Veronique , Fontanesi Luca , Garreau Hervé , Heiman David , Johnson Jeremy , Mage Rose G. , Peng Ze , Queney Guillaume , Rogel-Gaillard Claire , Ruffier Magali , Searle Steve , Villafuerte Rafael , Xiong Anqi , Young Sarah , Forsberg-Nilsson Karin , Good Jeffrey M. , Lander Eric S. , Ferrand Nuno , Lindblad-Toh Kerstin , Andersson Leif
Published: August 2014

Rabbits softly swept to domestication

When people domesticate animals, they select for tameness and tolerance of humans. What else do they look for? To identify the selective pressures that led to rabbit domestication, Carneiro
et al.
sequenced a domestic rabbit genome and compared it to that of its wild brethren (see the Perspective by Lohmueller). Domestication did not involve a single gene changing, but rather many gene alleles changing in frequency between tame and domestic rabbits, known as a soft selective sweep. Many of these alleles have changes that may affect brain development, supporting the idea that tameness involves changes at multiple loci.

Science
, this issue p.
1074
; see also p.
1000
Large impacts around a solar-analog star in the era of terrestrial planet formation
Authors: Meng Huan Y. A. , Su Kate Y. L. , Rieke George H. , Stevenson David J. , Plavchan Peter , Rujopakarn Wiphu , Lisse Carey M. , Poshyachinda Saran , Reichart Daniel E.
Published: August 2014

A cosmic dust storm that came and went

Unseen planets may still kick up a lot of dust. While rocky exoplanets finish their growth, destructive collisions among them throw off clouds of fine debris that shine bright in the infrared. Meng
et al.
monitored the star ID8 with the
Spitzer
Space Telescope and observed a rapid thermal flareup and fadeout within only 2 years. This modulation is consistent with recent collisions among its orbiting protoplanets. Such dynamic variations in presumed planet-forming systems encourage more studies that exploit the real-time changes.

Science
, this issue p.
1032
On the origin of Peter Rabbit
Authors: Lohmueller Kirk E.
Published: August 2014

Domestication of rabbits led to changes across the genome, particularly in regions related to brain development

[Also see Report by

Carneiro
et al.

]
Glimpsing glass structure under pressure
Authors: Youngman Randall E.
Published: August 2014

Nuclear magnetic resonance spectroscopy of a glass under pressure adds to our understanding of network structure

[Also see Report by

Edwards
et al.

]
As volcano rumbles, scientists plan for aviation alerts
Authors: Gramling Carolyn
Published: August 2014

Ash sensors ready to deploy on ground, planes.
Supernova breaks the mold
Authors: Clery Daniel
Published: August 2014

A massive explosion in a nearby galaxy both confirms and confounds astronomers' expectations.
Use ofS-[2,3-Bispalmitoyiloxy-(2R)-Propyl]-R-Cysteinyl-Amido-Monomethoxy Polyethylene Glycol as an Adjuvant Improved Protective Immunity Associated with a DNA Vaccine Encoding Cu,Zn Superoxide Dismutase of Brucella abortus in Mice
Authors: Retamal-Díaz Angello , Riquelme-Neira Roberto , Sáez Darwin , Rivera Alejandra , Fernández Pablo , Cabrera Alex , Guzmán Carlos A. , Oñate Ángel
Published: August 2014

This study was conducted to evaluate the immunogenicity and protective efficacy of a DNA vaccine encodingBrucella abortusCu,Zn superoxide dismutase (SOD) using the Toll-like receptor 2/6 agonistS-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPPcysMPEG) as an adjuvant. Intranasal coadministration of BPPcysMPEG with a plasmid carrying the SOD-encoding gene (pcDNA-SOD) into BALB/c mice elicited antigen-specific humoral and cellular immune responses. Humoral responses were characterized by the stimulation of IgG2a and IgG1 and by the presence of SOD-specific secretory IgA in nasal and bronchoalveolar lavage fluids. Furthermore, T-cell proliferative responses and increased production of gamma interferon were also observed upon splenocyte restimulation with recombinant SOD. Cytotoxic responses were also stimulated, as demonstrated by the lysis of RB51-SOD-infected J774.A1 macrophages by cells recovered from immunized mice. The pcDNA-SOD/BPPcysMPEG formulation induced improved protection against challenge with the virulent strainB. abortus2308 in BALB/c mice over that provided by pcDNA-SOD, suggesting the potential of this vaccination strategy againstBrucellainfection.
DNA Microarray-Based Typing of Streptococcus agalactiae Isolates
Authors: Nitschke Heike , Slickers Peter , Müller Elke , Ehricht Ralf , Monecke Stefan
Published: August 2014

Streptococcus agalactiae
frequently colonizes the urogenital tract, and it is a major cause of bacterial septicemia, meningitis, and pneumonia in newborns. For typing purposes, a microarray targeting group B streptococcus (GBS) virulence-associated markers and resistance genes was designed and validated with reference strains, as well as clinical and veterinary isolates. Selected isolates were also subjected to multilocus sequence typing. It was observed that putative typing markers, such as alleles of the alpha-like protein or capsule types, vary independently of each other, and they also vary independently from the affiliation to their multilocus sequence typing (MLST)-defined sequence types. Thus, it is not possible to assign isolates to sequence types based on the identification of a single distinct marker, such as a capsule type or
alp
allele. This suggests the occurrence of frequent genomic recombination. For array-based typing, a set of 11 markers (
bac
,
alp
,
pil1
locus,
pepS8
,
fbsB
, capsule locus,
hylB
,
abiG
-I/-II plus
Q8DZ34
,
pil2
locus,
nss
plus
srr
plus
rogB2
, and
rgfC/A/D/B
) was defined that provides a framework for splitting the tested 448
S. agalactiae
isolates into 76 strains that clustered mainly according to MLST-defined clonal complexes. There was evidence for region- and host-specific differences in the population structure of
S. agalactiae
, as well as an overrepresentation of strains related to sequence type 17 among the invasive isolates. The arrays and typing scheme described here proved to be a convenient tool for genotyping large numbers of clinical/veterinary isolates and thus might help obtain insight into the epidemiology of
S. agalactiae
.
Investigating a Mystery Disease: Tales from a Viral Detective
Authors: Lipkin W. Ian
Published: August 2014

Viral outbreak investigation is challenging logistically as well as scientifically. In the context of addressing a fictional emerging viral disease, I describe the process of discovery, from the initial report of a problem through discussions of intellectual property and sample management, study design, management, experimental execution, and reporting of results.
Major Histocompatibility Complex Class I Downregulation Induced by Equine Herpesvirus Type 1 pUL56 Is through Dynamin-Dependent Endocytosis
Authors: Huang Teng , Lehmann Maik J. , Said Abdelrahman , Ma Guanggang , Osterrieder Nikolaus
Published: August 2014

Equine herpesvirus type 1 (EHV-1) downregulates cell surface expression of major histocompatibility complex class I (MHC-I) in infected cells. We have previously shown that pUL56 encoded by the EHV-1 ORF1 gene regulates the process (G. Ma, S. Feineis, N. Osterrieder, and G. R. Van de Walle, J. Virol. 86:3554–3563, 2012, doi:http://dx.doi.org/10.1128/JVI.06994-11). Here, we report that cell surface MHC-I in EHV-1-infected cells is internalized and degraded in the lysosomal compartment in a pUL56-dependent fashion. pUL56-induced MHC-I endocytosis required dynamin and tyrosine kinase but was independent of clathrin and caveolin-1, the main constituents of the clathrin- and raft/caveola-mediated endocytosis pathways, respectively. Downregulation of cell surface MHC-I was significantly inhibited by the ubiquitin-activating enzyme E1 inhibitor PYR41, indicating that ubiquitination is essential for the process. Finally, we show that downregulation is not specific for MHC-I and that other molecules, including CD46 and CD63, are also removed from the cell surface in a pUL56-dependent fashion.

IMPORTANCEWe show that alphaherpesvirus induces MHC-I downregulation through endocytosis, which is mediated by pUL56. The dynamin-dependent endocytic pathway is responsible for MHC-I internalization in infected cells. Furthermore, we discovered that this endocytic process can be disrupted by the inhibiting ubiquitin-activating E1 enzyme, which is indispensable for ubiquitination. Finally, pUL56 action extends to a number of cell surface molecules that are significant for host immunity. Therefore, the protein may exert a more general immunomodulatory effect.
Automated detection of physiologic deterioration in hospitalized patients
Authors: Evans R Scott , Kuttler Kathryn G , Simpson Kathy J , Howe Stephen , Crossno Peter F , Johnson Kyle V , Schreiner Misty N , Lloyd James F , Tettelbach William H , Keddington Roger K , Tanner Alden , Wilde Chelbi , Clemmer Terry P
Published: August 2014

Objective Develop and evaluate an automated case detection and response triggering system to monitor patients every 5 min and identify early signs of physiologic deterioration.

Materials and methods A 2-year prospective, observational study at a large level 1 trauma center. All patients admitted to a 33-bed medical and oncology floor (A) and a 33-bed non-intensive care unit (ICU) surgical trauma floor (B) were monitored. During the intervention year, pager alerts of early physiologic deterioration were automatically sent to charge nurses along with access to a graphical point-of-care web page to facilitate patient evaluation.

Results Nurses reported the positive predictive value of alerts was 91–100% depending on erroneous data presence. Unit A patients were significantly older and had significantly more comorbidities than unit B patients. During the intervention year, unit A patients had a significant increase in length of stay, more transfers to ICU (p = 0.23), and significantly more medical emergency team (MET) calls (p = 0.0008), and significantly fewer died (p = 0.044) compared to the pre-intervention year. No significant differences were found on unit B.

Conclusions We monitored patients every 5 min and provided automated pages of early physiologic deterioration. This before–after study found a significant increase in MET calls and a significant decrease in mortality only in the unit with older patients with multiple comorbidities, and thus further study is warranted to detect potential confounding. Moreover, nurses reported the graphical alerts provided information needed to quickly evaluate patients, and they felt more confident about their assessment and more comfortable requesting help.
Ureteral metastasis from prostate cancer
Authors: Hongo Hiroshi , Kosaka Takeo , Yoshimine Shunsuke , Oya Mototsugu
Published: August 2014

A 59-year-old man had an elevated prostate-specific antigen (PSA) concentration (439 ng/mL) in December 2008. We diagnosed prostatic adenocarcinoma by prostate needle biopsy. CT and MRI showed a prostatic tumour with bone and lymph node metastases. Combined androgen blockade therapy reduced the PSA level temporarily. After the PSA level gradually started to increase again and reached 27.27 ng/mL in October 2010, the patient was diagnosed with castration-resistant prostate cancer and treated with docetaxel chemotherapy. Radiological examination detected left hydronephrosis and a tumour in the left lower ureter in March 2011. Retrograde pyelography and urine cytology of class 3 from the left ureter indicated that the ureteral mass was a urothelial carcinoma. A left nephroureterectomy was performed. After the operation, the pathological examination showed a metastatic prostate carcinoma, accompanied by a decrease in the serum PSA level from 59.56 to 45.33 ng/mL.
A 6-year comparative economic evaluation of healthcare costs and mortality rates of Dutch patients from conventional and CAM GPs
Authors: Baars Erik W , Kooreman Peter
Published: August 2014

Objectives

To compare healthcare costs and mortality rates of Dutch patients with a conventional (CON) general practitioner (GP) and patients with a GP who has additionally completed training in complementary and alternative medicine (CAM).

Design

Comparative economic evaluation.

Setting

Database from the Dutch insurance company Agis.

Participants

1 521 773 patients (98.8%) from a CON practice and 18 862 patients (1.2%) from a CAM practice.

Main outcome measures

Annual information on five types of healthcare costs for the years 2006–2011: care by GP, hospital care, pharmaceutical care, paramedic care and care covered by supplementary insurance. Healthcare costs in the last year of life. Mortality rates.

Results

The mean annual compulsory and supplementary healthcare costs of CON patients are respectively €1821 (95% CI 1813 to 1828) and €75.3 (95% CI 75.1 to 75.5). Compulsory healthcare costs of CAM patients are €225 (95% CI 169 to 281; p<0.001; 12.4%) lower and result mainly from lower hospital care costs (€165; 95% CI 118 to 212; p<0.001) and lower pharmaceutical care costs (€58; 95% CI 41 to 75; p<0.001), especially in the age categories 25–49 and 50–74 years. The costs in the last year of life of patients with CAM, GPs are €1161 (95% CI −138 to 2461; p<0.1) lower. This difference is entirely due to lower hospital costs (€1250; 95% CI 19 to 2481; p<0.05). The mean annual supplementary costs of CAM patients are €33 (95% CI 30 to 37; p<0.001; 44%) higher. CAM patients do not have lower or higher mortality rates than CON patients.

Conclusions

Dutch patients whose GP additionally completed training in CAM on average have €192 (10.1%) lower annual total compulsory and supplementary healthcare costs and do not live longer or shorter than CON patients.
Parent skills training for parents of children or adults with developmental disorders: systematic review and meta-analysis protocol
Authors: Reichow Brian , Kogan Cary , Barbui Corrado , Smith Isaac , Yasamy M Taghi , Servili Chiara
Published: August 2014

Introduction

Developmental disorders, including intellectual disability and autism spectrum disorders, may limit an individual's capacity to conduct daily activities. The emotional and economic burden on families caring for an individual with a developmental disorder is substantial, and quality of life may be limited by a lack of services. Therefore, finding effective treatments to help this population should be a priority. Recent work has shown parent skills training interventions improve developmental, behavioural and family outcomes. The purpose of this review protocol is to extend previous findings by systematically analysing randomised controlled trials of parent skills training programmes for parents of children with developmental disorders including intellectual disabilities and autism spectrum disorders and use meta-analytic techniques to identify programme components reliably associated with successful outcomes of parent skills training programmes.

Methods and analysis

We will include all studies conducted using randomised control trials designs that compare a group of parents receiving a parent skills training programme to a group of parents in a no-treatment control, waitlist control or treatment as usual comparison group. To locate studies, we will conduct an extensive electronic database search and then use snowball methods, with no limits to publication year or language. We will present a narrative synthesis including visual displays of study effects on child and parental outcomes and conduct a quantitative synthesis of the effects of parent skills training programmes using meta-analytic techniques.

Ethics and dissemination

No ethical issues are foreseen and ethical approval is not required given this is a protocol for a systematic review. The findings of this study will be disseminated through peer-reviewed publications and international conference presentations. Updates of the review will be conducted, as necessary, to inform and guide practice.

Trial registration number

PROSPERO (CRD42014006993).
Cost and turn-around time display decreases inpatient ordering of reference laboratory tests: a time series
Authors: Fang Daniel Z , Sran Gurmeet , Gessner Daniel , Loftus Pooja D , Folkins Ann , Christopher John Y , Shieh Lisa
Published: August 2014

Objective

Reference tests, also known as send-out tests, are commonly ordered laboratory tests with variable costs and turn-around times. We aim to examine the effects of displaying reference laboratory costs and turn-around times during computerised physician order entry (CPOE) on inpatient physician ordering behaviour.

Design

We conducted a prospective observational study at a tertiary care hospital involving inpatient attending physicians and residents. Physician ordering behaviour was prospectively observed between September 2010 and December 2012. An intervention was implemented to display cost and turn-around time for reference tests within our CPOE. We examined changes in the mean number of monthly physician orders per inpatient day at risk, the mean cost per order, and the average turn-around time per order.

Results

After our intervention, the mean number of monthly physician orders per inpatient day at risk decreased by 26% (51 vs 38, p<0.0001) with a decrease in mean cost per order (US$146.50 vs US$134.20, p=0.0004). There were no significant differences in mean turn-around time per order (5.6 vs 5.7 days, p=0.057). A stratified analysis of both cost and turn-around time showed significant decreases in physician ordering. The intervention projected a mean annual savings of US$330 439. Reference test cost and turn-around time variables were poorly correlated (r=0.2). These findings occurred in the setting of non-significant change to physician ordering in a control cohort of non-reference laboratory tests.

Conclusions

Display of reference laboratory cost and turn-around time data during real-time ordering may result in significant decreases in ordering of reference laboratory tests with subsequent cost savings.