bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the Leaky Pipeline: Perceived Barriers to Pursuing a Career in Medicine or Dentistry Among Underrepresented-in-Medicine Undergraduate Students
Authors: Freeman Brandi Kaye , Landry Alden , Trevino Robert , Grande David , Shea Judy A.
Published: December 2015

Purpose

Representation of persons from diverse backgrounds remains a persistent challenge for medicine and dentistry workforces. Past research has focused on quantifying factors such as markers of educational achievement to explain the difficulty of increasing diversity within the professions. There has been less effort toward understanding the perspectives of undergraduate students on the threshold of applying to medical/dental school about distinct barriers to pursuing a medical or dental career and continuing through the training pipeline.

Method

In 2012 and 2013, the authors conducted a qualitative study of undergraduate students participating in the Tour for Diversity in Medicine, a program where minority physicians and dentists visit colleges with large fractions of minority students to encourage careers in the health professions. Focus groups were convened during the visits to examine perceived barriers to pursuing careers in medicine and dentistry and challenges identified through thematic content analysis.

Results

Eighty-two students participated in discussions at 11 colleges visited between September 2012 and February 2013. Students described challenges including inadequate institutional resources (e.g., sparse clinical opportunities), strained personal resources (e.g., conflict arising from familial pressure), inadequate guidance and mentoring to assist with key career decisions, and societal barriers. For participants, these challenges caused them to question the viability of persisting in the pipeline to a medical or dental career.

Conclusions

Solving the issue of diversity in medicine and dentistry is multifaceted, but elucidated challenges from the undergraduate student perspective offer targeted areas where intervention may help remedy barriers and decrease pipeline leakiness.
Preoperative Score to Predict Postoperative Mortality (POSPOM)
Authors: Le Manach Yannick , Collins Gary , Rodseth Reitze , Le Bihan-Benjamin Christine , Biccard Bruce , Riou Bruno , Devereaux P.J. , Landais Paul
Published: December 2015

Background

An accurate risk score able to predict in-hospital mortality in patients undergoing surgery may improve both risk communication and clinical decision making. The aim of the study was to develop and validate a surgical risk score based solely on preoperative information, for predicting in-hospital mortality.

Methods

From January 1, 2010, to December 31, 2010, data related to all surgeries requiring anesthesia were collected from all centers (single hospital or hospitals group) in France performing more than 500 operations in the year on patients aged 18 yr or older (n = 5,507,834). International Statistical Classification of Diseases, 10th revision codes were used to summarize the medical history of patients. From these data, the authors developed a risk score by examining 29 preoperative factors (age, comorbidities, and surgery type) in 2,717,902 patients, and then validated the risk score in a separate cohort of 2,789,932 patients.

Results

In the derivation cohort, there were 12,786 in-hospital deaths (0.47%; 95% CI, 0.46 to 0.48%), whereas in the validation cohort there were 14,933 in-hospital deaths (0.54%; 95% CI, 0.53 to 0.55%). Seventeen predictors were identified and included in the PreOperative Score to predict PostOperative Mortality (POSPOM). POSPOM showed good calibration and excellent discrimination for in-hospital mortality, with a c-statistic of 0.944 (95% CI, 0.943 to 0.945) in the development cohort and 0.929 (95% CI, 0.928 to 0.931) in the validation cohort.

Conclusion

The authors have developed and validated POSPOM, a simple risk score for the prediction of in-hospital mortality in surgical patients.
Epigenetic Manipulation of Brain-derived Neurotrophic Factor Improves Memory Deficiency Induced by Neonatal Anesthesia in Rats
Authors: Wu Jiang , Bie Bihua , Naguib Mohamed
Published: December 2015

AbstractAbstract

The authors found a substantial reduction of hippocampal brain-derived neurotrophic factor resulting from the transcriptional factors–mediated epigenetic modification in the promoter region of Bdnf exon IV in rats exposed postnatally to anesthetic drugs. This brain-derived neurotrophic factor reduction led to the insufficient drive for the synthesis of synaptic proteins, thus contributing to the hippocampal synaptic and cognitive dysfunction induced by neonatal anesthesia. These effects were mitigated by the exposure to an enriched environment.

Background

Although neonatal exposure to anesthetic drugs is associated with memory deficiency in rodent models and possibly in pediatric patients, the underlying mechanisms remain elusive. The authors tested their hypothesis that exposure of the developing brain to anesthesia triggers epigenetic modification, involving the enhanced interaction among transcription factors (histone deacetylase 2, methyl-cytosine-phosphate-guanine–binding protein 2, and DNA methyltransferase 1) in Bdnf promoter region(s) that inhibit brain-derived neurotrophic factor (BDNF) expression, resulting in insufficient drive for local translation of synaptic mRNAs. The authors further hypothesized that noninvasive environmental enrichment (EE) will attenuate anesthesia-induced epigenetic inhibition of BDNF signaling and memory loss in rodent models.

Methods

Seven days after birth (P7), neonatal rats were randomly assigned to receive either isoflurane anesthesia for 6 h or sham anesthesia. On P21, pups were weaned, and animals were randomly assigned to EE or a standard cage environment (no EE). Behavioral, molecular, and electrophysiological studies were performed on rats on P65.

Results

The authors found a substantial reduction of hippocampal BDNF (n = 6 to 7) resulting from the transcriptional factors–mediated epigenetic modification in the promoter region of Bdnf exon IV in rats exposed postnatally to anesthetic drugs. This BDNF reduction led to the insufficient drive for the synthesis of synaptic proteins (n = 6 to 8), thus contributing to the hippocampal synaptic (n = 8 to 11) and cognitive dysfunction (n = 10) induced by neonatal anesthesia. These effects were mitigated by the exposure to an enriched environment.

Conclusions

The findings of this study elucidated the epigenetic mechanism underlying memory deficiency induced by neonatal anesthesia and propose EE as a potential therapeutic approach.
IV and Perineural Dexmedetomidine Similarly Prolong the Duration of Analgesia after Interscalene Brachial Plexus Block
Authors: Abdallah Faraj W. , Dwyer Tim , Chan Vincent W. S. , Niazi Ahtsham U. , Ogilvie-Harris Darrell J. , Oldfield Stephanie , Patel Rajesh , Oh Justin , Brull Richard
Published: December 2015

AbstractAbstract

In 99 patients receiving interscalene block with 15 ml ropivacaine, 0.5%, with 0.5 μg/kg dexmedetomidine prolonged the blockade and reduced the 24-h opioid use compared with placebo control, and these effects were similar whether dexmedetomidine was administered intravenously or perineurally.

Background

Perineural and IV dexmedetomidine have each been suggested to prolong the duration of analgesia when administered in conjunction with peripheral nerve blocks. In the first randomized, triple-masked, placebo-controlled trial to date, the authors aimed to define and compare the efficacy of perineural and IV dexmedetomidine in prolonging the analgesic duration of single-injection interscalene brachial plexus block (ISB) for outpatient shoulder surgery.

Methods

Ninety-nine patients were randomized to receive ISB using 15 ml ropivacaine, 0.5%, with 0.5 μg/kg dexmedetomidine administered perineurally (DexP group), intravenously (DexIV group), or none (control group). The authors sequentially tested the joint hypothesis that dexmedetomidine prolongs the duration of analgesia and reduces the 24-h cumulative postoperative morphine consumption. Motor blockade, pain severity, hemodynamic variations, opioid-related side effects, postoperative neurologic symptoms, and patient satisfaction were also evaluated.

Results

Ninety-nine patients were analyzed. The duration of analgesia was 10.9 h (10.0 to 11.8 h) and 9.8 h (9.0 to 10.6 h) for the DexP and DexIV groups, respectively, compared with 6.7 h (5.6 to 7.8) for the control group (P < 0.001). Dexmedetomidine also reduced the 24-h cumulative morphine consumption to 63.9 mg (58.8 to 69.0 mg) and 66.2 mg (60.6 to 71.8 mg) for the DexP and DexIV groups, respectively, compared with 81.9 mg (75.0 to 88.9 mg) for the control group (P < 0.001). DexIV was noninferior to DexP for these outcomes. Both dexmedetomidine routes reduced the pain and opioid consumption up to 8 h postoperatively and did not prolong the duration of motor blockade.

Conclusion

Both perineural and IV dexmedetomidine can effectively prolong the ISB analgesic duration and reduce the opioid consumption without prolonging motor blockade.
PGE1 Attenuates IL-1β-induced NGF Expression in Human Intervertebral Disc Cells
Authors: Murata Kazuma , Sawaji Yasunobu , Alimasi Wuqikun , Suzuki Hidekazu , Endo Kenji , Tanaka Hidetoshi , Yorifuji Makiko , Kosaka Taiichi , Shishido Takaaki , Yamamoto Kengo
Published: December 2015

Study Design.

In vitro study using isolated human intervertebral disc (IVD) cells.

Objective.

To investigate the effects of prostaglandin (PG)E1 and its orally available derivative limaprost on the regulation of nerve growth factor (NGF) expression and to compare their actions with other prostanoids using interleukin (IL)-1-stimulated human IVD cells.

Summary of Background Data.

We previously reported that a selective COX-2 inhibitor enhanced, whereas PGE2 suppressed the induction of NGF by IL-1 in human IVD cells, and proposed that PGE2 can suppress NGF expression by a negative feedback mechanism.

Methods.

Isolated human IVD cells were stimulated with IL-1 in the presence or absence of increasing concentrations of PGE2, PGE1, limaprost, PGI2, PGD2, or PGF2α (10–10,000 nM). For some experiments, an E-series prostanoid receptor (EP)4 antagonist (L-161,982) was added prior to the stimulation. NGF expression was determined by real-time polymerase chain reaction and its protein level was quantified by enzyme-linked immunosorbent assay.

Results.

PGE2, PGE1, and limaprost inhibited the IL-1-mediated induction of NGF in a concentration-dependent manner, with IC50 values of 9.9, 10.6, and 70.9 nM, respectively. PGI2 also suppressed NGF expression but to a much less extent. PGD2, on the other hand, significantly enhanced NGF expression, whereas PGF2α had no effect. Protein expression levels of NGF mirrored its mRNA levels. The suppression of NGF expression by PGE2 and PGE1 was partly reversed by L-161,982.

Conclusion.

PGE1 and limaprost exhibited a novel pharmacological action that suppresses NGF expression in human IVD cells, and other prostanoids differentially regulated NGF expression. Limaprost has been used to treat patients with lumbar spinal stenosis in Japan and was proved to be effective in relieving symptoms. Our in vitro results may explain, in part, the mechanism of action of limaprost for low back pain.

Level of Evidence: N/A
Changes in Whole-Body Oxygen Consumption and Skeletal Muscle Mitochondria During Linezolid-Induced Lactic Acidosis
Authors: Protti Alessandro , Ronchi Dario , Bassi Gabriele , Fortunato Francesco , Bordoni Andreina , Rizzuti Tommaso , Fumagalli Roberto
Published: December 2015

Objective:

To better clarify the pathogenesis of linezolid-induced lactic acidosis.

Design:

Case report.

Setting:

ICU.

Patient:

A 64-year-old man who died with linezolid-induced lactic acidosis.

Interventions:

Skeletal muscle was sampled at autopsy to study mitochondrial function.

Measurements and Main Results:

Lactic acidosis developed during continuous infusion of linezolid while oxygen consumption and oxygen extraction were diminishing from 172 to 52 mL/min/m2 and from 0.27 to 0.10, respectively. Activities of skeletal muscle respiratory chain complexes I, III, and IV, encoded by nuclear and mitochondrial DNA, were abnormally low, whereas activity of complex II, entirely encoded by nuclear DNA, was not. Protein studies confirmed stoichiometric imbalance between mitochondrial (cytochrome c oxidase subunits 1 and 2) and nuclear (succinate dehydrogenase A) DNA–encoded respiratory chain subunits. These findings were not explained by defects in mitochondrial DNA or transcription. There were no compensatory mitochondrial biogenesis (no induction of nuclear respiratory factor 1 and mitochondrial transcript factor A) or adaptive unfolded protein response (reduced concentration of heat shock proteins 60 and 70).

Conclusions:

Linezolid-induced lactic acidosis is associated with diminished global oxygen consumption and extraction. These changes reflect selective inhibition of mitochondrial protein synthesis (probably translation) with secondary mitonuclear imbalance. One novel aspect of linezolid toxicity that needs to be confirmed is blunting of reactive mitochondrial biogenesis and unfolded protein response.
PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation
Authors: Elinzano Heinrich , Glantz Michael , Mrugala Maciej , Kesari Santosh , Piccioni David E. , Kim Lyndon , Pan Edward , Yunus Shakeeb , Coyle Thomas , Timothy Kinsella , Evans Devon , Mantripragada Kalyan , Boxerman Jerrold , DiPetrillo Thomas , Donahue John E. , Hebda Nicholas , Mitchell Kristen M. , Rosati Kayla L. , Safran Howard
Published: December 2015

Purpose:

Efficacy signals but substantial myelosuppression were demonstrated in a single arm phase II study of paclitaxel poliglumex (PPX) in combination with temozolomide (TMZ) and radiation therapy (RT) for first-line treatment of glioblastoma. The objective of this randomized phase II trial was to assess the efficacy and safety of single-agent PPX with RT (PPX/RT) versus TMZ with RT (TMZ/RT) for glioblastoma without O6-methylguanine-DNA methyltransferase (MGMT) methylation.

Materials and Methods:

Patients with glioblastoma with unmethylated MGMT without prior chemotherapy or RT were eligible. Patients were randomly assigned 2:1 to PPX, 50 mg/m2/wk for 6 weeks, or standard TMZ, with concurrent 60.0 Gy RT. One month after completion of chemoradiation all patients received standard maintenance TMZ. The primary endpoint was progression-free survival (PFS).

Results:

Of the 164 patients enrolled, 86 were MGMT unmethylated. Of these, 63 patients were randomized (42 to PPX/RT and 21 to TMZ/RT). Fifty-nine patients could be analyzed. The median PFS was 9 months in the PPX/RT group and 9.5 months in the TMZ/RT group (hazard ratio in the PPX/RT group, 1.10; 95% confidence interval, 0.79-2.08; P=0.75). Median overall survival was 16 versus 14.8 months for PPX/RT and TMZ/RT groups, respectively (hazard ratio, 1.44; 95% confidence interval, 0.75-2.77; P=0.27). In the PPX and TMZ groups 44% versus 22% of patients, respectively, experienced one or more grade 3 or higher toxicities during chemoradiation.

Conclusions:

PPX/RT did not improve PFS or overall survival. This study provides an effective trial design for screening RT sensitizers in glioblastoma.
Effect of Head Tilt and Ocular Compensatory Mechanisms on Retinal Nerve Fiber Layer Measurements by Cirrus Spectral Domain and Spectralis Optical Coherence Tomography in Normal Subjects
Authors: Bin Ismail Muhammad A. , Hui Li Lilian Koh , Yap Sae Cheong , Yip Leonard W.
Published: December 2015

Purpose:

To determine the effect of head tilt and ocular compensatory mechanisms on retinal nerve fiber layer (RNFL) thickness measurements using the Cirrus and Spectralis spectral-domain optical coherence tomography (OCT) in healthy eyes. Our secondary objective was to assess the visual influence on ocular compensatory mechanisms during head tilt.

Materials and Methods:

This is a prospective, observational study. A single randomly selected eye was scanned undilated in 3 positions (baseline, right, and left tilt) using both machines. In addition, patching was also done for the contralateral eye during head tilt and RNFL measurements repeated. The paired t test was used to analyze effect on RNFL thickness. One-way repeated-measures analysis of variance was used to compare differences in RNFL measurements.

Results:

In Cirrus OCT RNFL analysis, ipsilateral head tilt resulted in superior thinning and temporal thickening, whereas contralateral head tilt resulted in inferior thinning, nasal thickening, as well as temporal thickening (all P<0.05). Head tilt did not cause any significant change in RNFL thickness with Spectralis OCT (P>0.05). Patching the contralateral eye also did not alter Cirrus RNFL measurement errors due to head tilt.

Conclusions:

Head tilt can affect the measurement of the RNFL thickness in Cirrus OCT, and ocular compensatory mechanisms were not sufficient to prevent this. In contrast, Spectralis OCT RNFL thickness measurements were not affected by head tilt. Patching the contralateral eye during head tilt in Cirrus OCT also did not affect RNFL variability. The visual influence on ocular compensatory mechanisms during head tilt appears insignificant.
Spray Dried, Pasteurised Bovine Colostrum Protects Against Gut Dysfunction and Inflammation in Preterm Pigs
Authors: St⊘y Ann Cathrine F. , Sangild Per T. , Skovgaard Kerstin , Thymann Thomas , Bjerre Mette , Chatterton Dereck E.W. , Purup Stig , Boye Mette , Heegaard Peter M.H.
Published: December 2015

Objective:

Feeding bovine colostrum (BC) improves gut maturation and function and protects against necrotizing enterocolitis, relative to formula in newborn preterm pigs. Before BC can be used for preterm infants, it is important to test if the milk processing, required to reduce bacterial load and increase shelf life, may affect bioactivity and efficacy of a BC product.

Methods:

We investigated if spray dried, pasteurised BC had protective effects on gut function in preterm pigs, relative to formula. After a 2‐day total parenteral nutrition period, preterm pigs were fed formula for a few hours (to induce a proinflammatory state) followed by 2 days of formula (FORM, n = 14), BC (colostrum [COLOS], n = 14), spray‐dried BC (POW, n = 8), or pasteurised, spray‐dried BC (POWPAS, n = 9).

Results:

Spray drying and pasteurisation of BC decreased the concentration of transforming growth factor‐β1, ‐β2 and increased protein aggregation. All of the 3 BC groups had reduced necrotizing enterocolitis severity, small intestinal levels of IL‐1β, ‐8, and colonic lactic acid levels, and increased intestinal villus height, hexose absorption, and digestive enzyme activities, relative to the FORM group (all P < 0.05). All of the 3 BC diets stimulated epithelial cell migration in a wound‐healing model with IEC‐6 cells.

Conclusions:

Spray drying and pasteurisation affect BC proteins, but do not reduce the trophic and anti‐inflammatory effects of BC on the immature intestine. It remains to be studied if BC products will benefit preterm infants just after birth when human milk is often not available.
Does Gastrostomy Placement With Concurrent Fundoplication Increase the Risk of Gastrostomy‐related Complications?
Authors: Thomas Christine , Forrest Alison , Klingberg Hannah , Moore David , Abu‐Assi Rammy , Barry Simon C. , Khurana Sanjeev
Published: December 2015

Objective:

To compare the incidence of complications with a primary gastrostomy versus gastrostomy with concurrent fundoplication and evaluating the impact of the method of gastrostomy tube placement. Neurologically impaired children were compared with neurologically normal children. Two low profile devices were compared for longevity.

Methods:

Ninety‐eight patients (58 boys, mean age 4.66 years) with 107 gastrostomies inserted between April 2004 and May 2008 were included in this retrospective, single institution audit. Minimum follow‐up period was 1 year. Specific complications reviewed were tube and site related. Logistic regression analysis examined the relationship between complications, type of procedure, method of placement, and neurological status. Survival analysis with log‐rank test was used to compare the duration of the low‐profile devices.

Results:

There were 63 primary gastrostomies and 44 with concurrent fundoplication, 71 children were neurologically impaired. Mean (±SD) follow‐up time was 35.6 ± 1.4 months. There was a significant association between concurrent gastrostomy insertion with fundoplication and incidence of infection (odds ratio = 2.4, 95% confidence interval (CI) 1.02–5.56, P = 0.02) and excoriation (odds ratio = 2.5, 95% CI 1.09–5.71, P = 0.015). There were no associations between the complications with gastrostomy placement and neurological status. Failure rate of the balloon device was significantly greater than the fixed bolster device with a Hazard Ratio for survival of 3.2 (95% CI 2.2–4.6).

Conclusions:

Gastrostomy site‐related problems were more common than generally reported. There was a higher incidence of site infection and skin excoriation for gastrostomy placement with concurrent fundoplication. There was no significant difference in complications between the method of gastrostomy placement or neurological status. Balloon devices were changed 3 times more often than bolster retention devices.
Association of Macrophages With Angiogenesis in Oral Epithelial Dysplasia, Oral Verrucous Carcinoma, and Oral Squamous Cell Carcinoma: An Immunohistochemical Study
Authors: Chawla Himanshi , Urs Aadithya B. , Augustine Jeyaseelan
Published: December 2015

The present study aimed to elucidate the role of tumor-associated macrophages (TAMs) and angiogenesis in tumor progression by assessing their immunohistochemical expression in oral epithelial dysplasia (OED), oral verrucous carcinoma (OVC), and oral squamous cell carcinoma (OSCC). About 20 histopathologically confirmed cases of OED, OVC, and OSCC each and 10 cases of normal oral mucosa taken as controls were stained immunohistochemically using CD68 and CD31 antibodies. The average TAM count and the microvessel density (MVD) were calculated for each group and expressed as mean±SD and compared using the Mann-WhitneyUTest. Pearson correlation was applied to assess the correlation between TAM and MVD in different groups. The CD68 count was found to be significantly higher in all the groups as compared with controls, with the highest counts in OSCC, followed by OED and OVC. MVD was significantly higher in all the test groups as compared with controls. The increase in MVD was highly significant in OSCC as compared with OVC, and in OVC as compared with OED. No association could be determined between TAM and MVD. There does not seem to be any direct influence of macrophages on angiogenesis in the microenvironment of OED, OVC, and OSCC.
Immunohistochemical Performance of Estrogen and Progesterone Receptor Antibodies on the Dako Omnis Staining Platform: Evaluation in Multicenter Studies
Authors: Hicks David , Dell’Orto Patrizia , Falzon Mary , Hoff Kirsten D. , Levy Yaron Y. , McMahon Loralee , Miller Keith , Russo Leila , Viale Giuseppe
Published: December 2015

The analysis of estrogen receptor (ER) and progesterone receptor (PR) expression levels by immunohistochemistry is an important part of the initial evaluation of breast cancer and critically important in treatment planning. Anti-ERα (clone EP1) and anti-PR (clone PgR 1294) antibodies are in development for the Dako Omnis automated staining platform. These antibodies are not yet commercially available and are in performance evaluation, including the 4 international, multicenter studies reported here. For each antibody, a reproducibility study and a method comparison study was done in a randomized manner in order to test the antibodies under conditions closest to real-world user conditions. The reproducibility studies included 5 staining runs on the Dako Omnis with 20 formalin-fixed and paraffin-embedded human breast carcinoma specimens in 3 independent laboratories, and the method comparison studies included several hundred specimens stained on the Dako Omnis and on the Autostainer Link 48 platforms. Stained slides were evaluated for nuclear ER or PR expression according to American Society of Clinical Oncology/College of American Pathologists guidelines (≥1% cut-off for positive) by pathologists who were blinded from the staining method and specimen ID. For both anti-ERα (clone EP1) and anti-PR (clone PgR 1294) on the Dako Omnis, high reproducibility agreement rates were obtained on the interrun, interlaboratory, and interobserver endpoints. High concordance rates were observed between the specimens stained on the Dako Omnis platform and the Autostainer Link 48 platform. Staining quality was excellent for both anti-ERα (clone EP1) and anti-PR (clone PgR 1294) on the Dako Omnis. These results suggest that these antibodies are reliable and reproducible tools for immunohistochemistry analysis of ER and PR expression levels in formalin-fixed and paraffin-embedded breast carcinoma tissues on the Dako Omnis platform.
Nanopore Sequencing in Microgravity
Authors: McIntyre Alexa B.R. , Rizzardi Lindsay , Yu Angela M , Rosen Gail L. , Alexander Noah , Botkin Douglas J. , John Kristen K. , Castro-Wallace Sarah L. , Burton Aaron S. , Feinberg Andrew , Mason Christopher E.
Published: December 2015

The ability to perform remote,in situsequencing and diagnostics has been a long-sought goal for point-of-care medicine and portable DNA/RNA measurements. This technological advancement extends to missions beyond Earth as well, both for crew health and astrobiology applications. However, most commercially available sequencing technologies are ill-suited for space flight for a variety of reasons, including excessive volume and mass, and insufficient ruggedization for spaceflight. Portable and lightweight nanopore-based sequencers, which analyze nucleic acids electrochemically, are inherently much better suited to spaceflight, and could potentially be incorporated into future missions with only minimal modification. As a first step toward evaluating the performance of nanopore sequencers in a microgravity environment, we tested the Oxford Nanopore Technologies MinIONTMin a parabolic flight simulator to examine the effect of reduced gravity on DNA sequencing. The instrument successfully generated three reads, averaging 2,371 bases. However, the median current was shifted across all reads and the error profiles changed compared with operation of the sequencer on the ground, indicating that distinct computational methods may be needed for such data. We evaluated existing methods and propose two new methods; the first new method is based on a wave-fingerprint method similar to that of the Shazam model for matching periodicity information in music, and the second is based on entropy signal mapping. These tools provide a unique opportunity for nucleic acid sequencing in reduced gravity environments. Finally, we discuss the lessons learned from the parabolic flight as they would apply to performing DNA sequencing with the MinIONTMaboard the International Space Station.
Combating the scientific decline effect with confidence (intervals)
Authors: Groppe David M.
Published: December 2015

A symptom of the need for greater reproducibility in scientific practice is the “decline effect,” the fact that the size of many experimental effects decline with subsequent study or fail to replicate entirely. A simple way to combat this problem is for scientists to more routinely use confidence intervals (CIs) in their work. CIs provide frequentist bounds on the true size of an effect and can reveal when a statistically significant effect is possibly too small to be reliable or when a large effect might have been missed due to insufficient statistical power. CIs are often lacking in psychophysiological reports, likely due to the large number of dependent variables, which complicates deriving and visualizing CIs. In this article, I explain the value of CIs and show how to compute them for analyses involving multiple variables in various ways that adjust the intervals for the greater uncertainty induced by multiple statistical comparisons. The methods are illustrated using a basic visual oddball event-related potential (ERP) dataset and freely available Matlab software.
Ritornello: High fidelity control-free chip-seq peak calling
Authors: Stanton Kelly Patrick , Jin Jiaqi , Weissman Sherman , Kluger Yuval
Published: December 2015

With the advent of next generation high-throughput DNA sequencing technologies, omics experiments have become the mainstay for studying diverse biological effects on a genome wide scale. ChIP-seq is the omics technique that enables genome wide localization of transcription factor binding or epigenetic modification events. Since the inception of ChIP-seq in 2007, many methods have been developed to infer ChIP target binding loci from the resultant reads after mapping them to a reference genome. However, interpreting these data has proven challenging, and as such these algorithms have several shortcomings, including susceptibility to false positives due to artifactual peaks, poor localization of binding sites, and the requirement for a total DNA input control which increases the cost of performing these experiments. We present Ritornello, a new approach with roots in digital signal processing (DSP) that addresses all of these problems. We show that Ritornello generally performs equally or better than the peak callers tested and recommended by the ENCODE consortium, but in contrast, Ritornello does not require a matched total DNA input control to avoid false positives, effectively decreasing the sequencing cost to perform ChIP-seq.
SSA.ME Detection of cancer mutual exclusivity patterns by small subnetwork analysis
Authors: Pulido-Tamayo Sergio , Weytjens Bram , De Maeyer Dries , Marchal Kathleen
Published: December 2015

Because of its clonal evolution a tumor rarely contains multiple genomic alterations in the same pathway, as disrupting the pathway by one gene often is sufficient to confer the complete fitness advantage. As a result mutated genes display patterns of mutual exclusivity across tumors. The identification of such patterns have been exploited to detect cancer drivers. The complex problem of searching for mutual exclusivity across individuals has previously been solved by filtering the input data upfront, analyzing only genes mutated in numerous samples. These stringent filtering criteria come at the expense of missing rarely mutated driver genes. To overcome this problem, we present SSA.ME, a network-based method to detect mutually exclusive genes across tumors that does not depend on stringent filtering. Analyzing the TCGA breast cancer dataset illustrates the added value of SSA.ME: despite not using mutational frequency based-prefiltering, well-known recurrently mutated drivers could still be highly prioritized. In addition, we prioritized several genes that displayed mutual exclusivity and pathway connectivity with well-known drivers, but that were rarely mutated. We expect the proposed framework to be applicable to other complex biological problems because of its capability to process large datasets in polynomial time and its intuitive implementation.
LEAFY COTYLEDON1-CASEIN KINASE I-TCP15-PHYTOCHROME INTERACTING FACTOR4 Network Regulates Somatic Embryogenesis by Regulating Auxin Homeostasis
Authors: Min Ling , Hu Qin , Li Yaoyao , Xu Jiao , Ma Yizan , Zhu Longfu , Yang Xiyan , Zhang Xianlong
Published: December 2015

Somatic embryogenesis (SE) is an efficient tool for the propagation of plant species and also, a useful model for studying the regulatory networks in embryo development. However, the regulatory networks underlying the transition from nonembryogenic callus to somatic embryos during SE remain poorly understood. Here, we describe an upland cotton (Gossypium hirsutum) CASEIN KINASE I gene, GhCKI, which is a unique key regulatory factor that strongly affects SE. Overexpressing GhCKI halted the formation of embryoids and plant regeneration because of a block in the transition from nonembryogenic callus to somatic embryos. In contrast, defective GhCKI in plants facilitated SE. To better understand the mechanism by which GhCKI regulates SE, the regulatory network was analyzed. A direct upstream negative regulator protein, cotton LEAFY COTYLEDON1, was identified to be targeted to a cis-element, CTTTTC, in the promoter of GhCKI. Moreover, GhCKI interacted with and phosphorylated cotton CINCINNATA-like TEOSINTE BRANCHED1-CYCLOIDEA-PCF transcription factor15 by coordinately regulating the expression of cotton PHYTOCHROME INTERACTING FACTOR4, finally disrupting auxin homeostasis, which led to increased cell proliferation and aborted somatic embryo formation in GhCKI-overexpressing somatic cells. Our results show a complex process of SE that is negatively regulated by GhCKI through a complex regulatory network.
Probing the absolute scattering intensity by means of a laboratory-based small-angle X-ray scattering camera using an imaging plate detector
Authors: Gutsche Alexander , Dingenouts Nico , Guo Xiaoai , Meier Manuel , Nirschl Hermann
Published: December 2015

This paper deals with the application of an imaging plate (IP) detector for probing absolute intensities in small-angle X-ray scattering experiments. The IP detector is used with an in-house modified Kratky camera. It is shown that the normalization of scattering data to the transmitted primary beam intensity properly compensates for various unwanted features typically associated with the IP detector,e.g.the fading effect and poorly reproducible scanning times, promoting precise absolute intensity calibration. The absolute intensity calibration was performed by measuring a large number of different silica sols serving as secondary standards. The calibration factor, which converts the measured data into absolute units, was determined by the average over the data obtained for different silica sols, providing a precise calibration of the IP detector. In particular, it is shown that silica sols do not require application of synchrotron radiation or a long exposure time as typically needed if pure liquids or standard proteins are used as secondary standards. To check the applicability of the IP detector in a real synthesis, Stöber silica particles were synthesized under various reaction conditions and the scattering intensity was probed and converted into absolute units. The volume fractions and the number densities of silica particles provided by the absolute intensities showed a good agreement with theoretical values predicted for the different reaction conditions. Therefore, the IP detector can be used for accurate probing of absolute intensities.
Caution regarding ambiguities in similar expressions of orientation relationships
Authors: Du Juan , Zhang Wen-Zheng , Dai Fu-Zhi , Shi Zhang-Zhi
Published: December 2015

The orientation relationship (OR) between two phases is an essential parameter to characterize microstructure in multiphase crystalline materials. Among the numerous ways to define an OR, the expression in terms of the parallelism between lattice planes and between directions from different phases, referred to as the {hkl}/〈uvw〉 expression, is the most commonly used. However, this expression scheme may be misleading because completely different ORs could be mistakenly regarded as equivalent ORs owing to the similarity of the expressions. In this article, the symmetries of the parallel elements were analyzed to clarify the conditions causing three cases. Namely, two similar expressions may describe two different ORs, two variants of a unique OR or exactly the same OR. This analysis helps not only to avoid ambiguities caused by the {hkl}/〈uvw〉 expression but also to specify how variants are defined with respect to a different matrix phase. Based on the result of the analysis, the expressions of variants for the Kurdjumow–Sachs and Nishiyama–Wassermann ORs between face-centred cubic and body-centred cubic systems for different matrix phases are provided. Examples are given together with stereographic projections to demonstrate different cases.
Crystal structure of ethyl (1RS,6SR)-4-(2-methyl-1H-imidazol-4-yl)-2-oxo-6-(2,3,5-trichlorophenyl)cyclohex-3-ene-1-carboxylate
Authors: Mohan Billava J. , Sarojini Balladka K. , Yathirajan Hemmige S. , Rathore Ravindranath , Glidewell Christopher
Published: December 2015

The title compound, C19H17Cl3N2O3, has been prepared in a cyclocondensation reaction between 2,3,5-trichlorobenzaldehye and 4-acetyl-2-methyl-1H-imidazole. The cyclohexenone ring adopts an envelope conformation with the C atom substituted by the trichlorophenyl ring as the flap. The mutuallytransester and aryl substituents both occupy equatorial sites. In the crystal, a combination of N—H...O and C—H...N hydrogen bonds links the molecules into ribbons of edge-fused centrosymmetric rings, which encloseR22(14) andR44(16) alternate ring motifs, propagating along theb-axis direction.
Crystal structure of the thermochromic bis(diethylammonium) tetrachloridocuprate(II) complex
Authors: Aldrich Emily P. , Bussey Katherine A. , Connell Jennifer R. , Reinhart Erin F. , Oshin Kayode D. , Mercado Brandon Q. , Oliver Allen G.
Published: December 2015

In the structure of the title complex salt, (Et2NH2)2[CuCl4], the asymmetric unit consists of four unique diethylammonium cations and three unique tetrachloridocuprate anions. Two of the three anions are located with their copper atoms on independent crystallographic twofold axes, while the remaining tetrachloridocuprate is located at a general position of the orthorhombic space groupP21212. Two of the three Cu atoms adopt a distorted square-planar/disphenoidal geometry and the third Cu atom has a regular square-planar coordination environment. The diethylammonium cations form an extensive hydrogen-bonded network through N—H...Cl interactions with the tetrachloridocuprate anions, resulting in a two-dimensional sheet-like hydrogen-bonded network parallel to theabdirection. The complex was observed to undergo a color shift from deep green at room temperature to pale yellow at temperatures above 328 K.
Crystal structures of three complexes of zinc chloride with tri-tert-butylphosphane
Authors: Finke Aaron D. , Gray Danielle L. , Moore Jeffrey S.
Published: December 2015

Under anhydrous conditions and in the absence of a Lewis-base solvent, a zinc chloride complex with tri-tert-butylphosphane as the μ-bridged dimer is formed,viz.di-μ-chlorido-bis[chloridobis(tri-tert-butylphosphane)zinc], [ZnCl4(C12H27P)2], (1), which features a nearly square-shaped (ZnCl)2cyclic core and whose Cl atoms interact weakly with C—H groups on the phosphane ligand. In the presence of THF, monomeric dichlorido(tetrahydrofuran-κO)(tri-tert-butylphosphane-κP)zinc, [ZnCl2(C4H8O)(C12H27P)] or [P(tBu3)(THF)ZnCl2], (2), is formed. This slightly distorted tetrahedral Zn complex has weak C—H...Cl interactions between the Cl atoms and phosphane and THF C—H groups. Under ambient conditions, the hydrolysed complex tri-tert-butylphosphonium aquatrichloridozincate 1,2-dichloroethane monosolvate, (C12H28P)[ZnCl3(H2O)]·C2H4Cl2or [HPtBu3]+[(H2O)ZnCl3]−·C2H4Cl2, (3), is formed. This complex forms chains of [(H2O)ZnCl3]−anions from hydrogen-bonding interactions between the water H atoms and Cl atoms that propagate along thebaxis.
Preparing a framework for two-stage target-cost arrangement formulation
Authors: Lahdenperä Pertti
Published: December 2015

Purpose

– Early involvement of the project team with the construction resources seems to be gaining popularity as it aims to improve the cost efficiency of a project as there is significantly more potential to influence the project solution at that point in time. The missing price during early involvement/selection and the principal-agent setting, however, tend to leave the project owner in doubt of the reasonableness of pricing when it is fixed only later after the joint design phase involving the service provider and the owner. The purpose of this paper is to find a solution for this challenge.

Design/methodology/approach

– A two-stage target-cost (2STC) arrangement has been proposed as the solution. In this model the service provider earns a bonus by suggesting a lower target cost than the reference set at the time of the involvement of the provider. The amount of bonus also impacts the cost over-run risk transferred to the service provider to avoid overly optimistic promises. The proposition encompassed just the basic idea, and did not really delve into actual model formulations and their functioning under practical realities. Therefore, the required work is presented here in the form of a conceptual, discursive study focusing on relevant theories and empirical findings from major investment projects.

Findings

– The study produces a requirement framework for the 2STC model to allow functioning models to be formulated and tested. The framework incorporates numerous requirements, constraints and a suggested path forward. For instance, while the model may not be manipulatable, it must incentivise the service provider to seek more cost-effective project solutions, be feasible also from the view of the project owner and adapt to various project risk profiles and ranges of efficiency improvements.

Research limitations/implications

– The study suggests more concrete model formulations to be provided under the guidance of the presented framework.

Originality/value

– The 2STC model is a unique concept and no comparable construct is known to exist. Besides the requirement framework, the study also strengthens the foundation of and need for the 2STC model by a thorough survey of its theoretical linkages. Accordingly, the study presented in this paper forms the second stage in the overall 2STC development process focused on benefiting project owners and the industry.
Formularising two-stage target-cost arrangements for use in practice
Authors: Lahdenperä Pertti
Published: December 2015

Purpose

– Early involvement of the project team with the construction resources seems to be gaining popularity as it aims to improve the cost efficiency of a project as there is significantly more potential to influence the project solution at that point in time. The missing price during early involvement/selection and the principal-agent setting, however, tend to leave the project owner in doubt of the reasonableness of pricing when it is fixed only later after the joint design phase involving the service provider and the owner. The purpose of this paper is to find a solution for this challenge.

Design/methodology/approach

– A two-stage target-cost (2STC) arrangement has been proposed as the solution. In this model the service provider earns a bonus by suggesting a lower target cost than the reference set at the time of the involvement of the provider. The amount of bonus also impacts the cost over-run risk transferred to the service provider to avoid overly optimistic promises. Besides the initial conceptualisation of the idea, earlier research has also produced a framework for developing and assessing alternative formulations of the 2STC model. By means of mathematical modelling and optimisation and critical review the work seeks to provide formulations that meet the set requirements.

Findings

– The study establishes concrete formulations that are believed to function as intended with certain reservations. Two potential mechanisms, the constant and variable share models, are generated and presented, and recommendations are given for their use in practice. In the former, the extent of cost efficiency improvement in the development phase has no impact on percentage shares, but in the latter the service provider’s relative development bonus and share of cost over-runs are the bigger, the bigger the improvement.

Research limitations/implications

– The study suggests piloting the formulations in carefully selected projects in order to discover their practical feasibility.

Originality/value

– The 2STC model is a unique concept and no comparable construct is known to exist. The study produced concrete formulations for a 2STC construct while ensuring and illustrating their functioning to avoid surprises in their use. The study presented in this paper forms the third stage in the overall 2STC development process focussed on benefiting project owners and the industry.
Cognitive, affective and behavioural responses in mall experience
Authors: Lucia-Palacios Laura , Pérez-López Raúl , Polo-Redondo Yolanda
Published: December 2015

Purpose

– The purpose of this paper is to identify specific cognitive and affective responses in mall experience, as well as their antecedents, moderators and behavioural outcomes.

Design/methodology/approach

– The paper is based on content analysis technique. Data were obtained through in-depth interviews conducted from February 2013 to January 2014.

Findings

– The study reports the identification of efficiency and confusion as cognitive responses, as well as frustration, stress, peacefulness and excitement as affective responses experienced during the shopping trip. These responses lead to behavioural outcomes that are time spent, buying intentions and repatronage intentions. Furthermore, the paper identifies the main antecedents of these responses and the moderators of their relationships.

Research limitations/implications

– The findings provide insights into the study of psychological responses in retailing and avenues for further research.

Practical implications

– This research offers practical implications for managers, related to the manipulation of mall characteristics in order to encourage positive cognitive and affective responses and avoid negative ones.

Originality/value

– Based on content analysis technique, the present paper proposes a theoretical framework to conceptualize mall experience, detecting specific cognitive and affective responses and their specific behavioural outcomes as well as moderators.
Exploring logistics-related environmental sustainability in large retailers
Authors: Björklund Maria , Forslund Helena , Persdotter Isaksson Maria
Published: December 2015

Purpose

– The purpose of this paper is to explore and illustrate ways in which the world’s largest retailers describe their logistics-related environmental considerations, their environmental indicators applied to measure the effects of these considerations and their environmental consciousness in their CSR reports.

Design/methodology/approach

– Classification models are developed via a literature review on logistics-related environmental considerations, indicators and consciousness. A content analysis approach is then applied to examine CSR reports from 12 of the world’s largest retailers.

Findings

– Few retailers show environmental considerations in all logistics activities, but purchasing is especially well described. Even if many retailers claim to use the Global Reporting Initiative (GRI) framework, no one uses is completely. Judging consciousness from CSR reports raised a number of questions.

Research limitations/implications

– A contribution to theory is the development of two classification models. The first provides a description structure for environmental considerations related to logistics activities. The second expands the GRI indicator framework by incorporating a structure for logistics activities.

Practical implications

– The classification models developed can be an important mean for managers and also consumers to judge the environmental sustainability of retailers by their CSR reports.

Social implications

– The study makes a social contribution with its input on sustainability and especially environmental issues.

Originality/value

– Few studies have focused upon environmentally sustainable logistics in retail chains, and even fewer address how to measure environmental sustainability in this context.