bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical imaging of tumor vascularity associated with proliferation and glucose metabolism in early breast cancer: clinical application of total hemoglobin measurements in the breast
Authors: Ueda Shigeto , Nakamiya Noriko , Matsuura Kazuo , Shigekawa Takashi , Sano Hiroshi , Hirokawa Eiko , Shimada Hiroko , Suzuki Hiroaki , Oda Motoki , Yamashita Yutaka , Kishino Osamu , Kuji Ichiei , Osaki Akihiko , Saeki Toshiaki
Published: October 2013

Background

Near-infrared optical imaging targeting the intrinsic contrast of tissue hemoglobin has emerged as a promising approach for visualization of vascularity in cancer research. We evaluated the usefulness of diffuse optical spectroscopy using time-resolved spectroscopic (TRS) measurements for functional imaging of primary breast cancer.

Methods

Fifty-five consecutive TNM stageI/II patients with histologically proven invasive ductal carcinoma and operable breast tumors (<5 cm) who underwent TRS measurements were enrolled. Thirty (54.5%) patients underwent 18F-fluoro-deoxy-glucose (FDG) positron emission tomography with measurement of maximum tumor uptake. TRS was used to obtain oxyhemoglobin, deoxyhemoglobin, and total hemoglobin (tHb) levels from the lesions, surrounding normal tissue, and contralateral normal tissue. Lesions with tHb levels 20% higher than those present in normal tissue were defined as “hotspots,” while others were considered “uniform.” The findings in either tumor type were compared with clinicopathological factors.

Results

“Hotspot” tumors were significantly larger (P = 0.002) and exhibited significantly more advanced TNM stage (P = 0.01), higher mitotic counts (P = 0.01) and higher levels of FDG uptake (P = 0.0004) compared with “uniform” tumors; however, other pathological variables were not significantly different between the two groups.

Conclusions

Optical imaging for determination of tHb levels allowed for measurement of tumor vascularity as a function of proliferation and glucose metabolism, which may be useful for prediction of patient prognosis and potential response to treatment.
Is deep brain stimulation a treatment option for anorexia nervosa?
Authors: Oudijn Marloes S , Storosum Jitschak G , Nelis Elise , Denys Damiaan
Published: October 2013

Anorexia nervosa (AN) is a severe psychiatric disorder with high rates of morbidity, comorbidity and mortality, which in a subset of patients (21%) takes on a chronic course. Since an evidence based treatment for AN is scarce, it is crucial to investigate new treatment options, preferably focused on influencing the underlying neurobiological mechanisms of AN. The objective of the present paper was to review the evidence for possible neurobiological correlates of AN, and to hypothesize about potential targets for Deep brain stimulation (DBS) as a treatment for chronic, therapy-refractory AN. One avenue for exploring new treatment options based on the neurobiological correlates of AN, is the search for symptomatologic and neurobiologic parallels between AN and other compulsivity- or reward-related disorders. As in other compulsive disorders, the fronto-striatal circuitry, in particular the insula, the ventral striatum (VS) and the prefrontal, orbitofrontal, temporal, parietal and anterior cingulate cortices, are likely to be implicated in the neuropathogenesis of AN. In this paper we will review the few available cases in which DBS has been performed in patients with AN (either as primary diagnosis or as comorbid condition). Given the overlap in symptomatology and neurocircuitry between reward-related disorders such as obsessive compulsive disorder (OCD) and AN, and the established efficacy of accumbal DBS in OCD, we hypothesize that DBS of the nucleus accumbens (NAc) and other areas associated with reward, e.g. the anterior cingulated cortex (ACC), might be an effective treatment for patients with chronic, treatment refractory AN, providing not only weight restoration, but also significant and sustained improvement in AN core symptoms and associated comorbidities and complications. Possible targets for DBS in AN are the ACC, the ventral anterior limb of the capsula interna (vALIC) and the VS. We suggest conducting larger efficacy studies that also explore the functional effects of DBS in AN.
Hematological and hepatic effects of vascular epidermal growth factor (VEGF) used to stimulate hair growth in an animal model
Authors: Gnann Laís Angelo , Castro Rafael Ferreira , Azzalis Ligia Ajaime , Feder David , Perazzo Fabio Ferreira , Pereira Edimar Cristiano , Rosa Paulo César Pires , Junqueira Virginia Berlanga Campos , Rocha Katya Cristina , Machado Carlos D’ Aparecida , Paschoal Francisco Camargo , de Abreu Luiz Carlos , Valenti Vitor Engrácia , Fonseca Fernando Luiz Affonso
Published: October 2013

Background

Alopecia areata is the hair loss usually reversible, in sharply defined areas. The treatment of alopecia using growth factors shows interesting activity in promoting hair growth. In this concept, VEGF (vascular endothelial growth factor) is a marker of angiogenesis, stimulating hair growth by facilitating the supply of nutrients to the hair follicle, increasing follicular diameter. The aim of this study was the evaluation of a topical gel enriched with VEGF liposomes on the hair growth stimulation and its toxicological aspects.

Methods

Mesocricetus auratus were randomly divided into three groups. Control group was treated with Aristoflex® gel, 1% group with the same gel but added 1% VEGF and 3% group with 3% VEGF. Biochemical, hematological and histological analyses were done.

Results

At the end of the experiment (15th day of VEGF treatment) efficacy was determined macroscopically by hair density dermatoscopy analysis, and microscopically by hair diameter analysis. They both demonstrated that hair of the VEGF group increased faster and thicker than control. On the other hand, biochemical and hematological results had shown that VEGF was not 100% inert.

Conclusions

VEGF increased hair follicle area, but more studies are necessary to confirm its toxicity.
The capability of endophytic fungi for production of hemicellulases and related enzymes
Authors: Robl Diogo , Delabona Priscila da Silva , Mergel Carla Montanari , Rojas Juan Diego , Costa Patrícia dos Santos , Pimentel Ida Chapaval , Vicente Vania Aparecida , da Cruz Pradella José Geraldo , Padilla Gabriel
Published: October 2013

Background

There is an imperative necessity for alternative sources of energy able to reduce the world dependence of fossil oil. One of the most successful options is ethanol obtained mainly from sugarcane and corn fermentation. The foremost residue from sugarcane industry is the bagasse, a rich lignocellulosic raw material uses for the production of ethanol second generation (2G). New cellulolytic and hemicellulytic enzymes are needed, in order to optimize the degradation of bagasse and production of ethanol 2G.

Results

The ability to produce hemicellulases and related enzymes, suitable for lignocellulosic biomass deconstruction, was explored using 110 endophytic fungi and 9 fungi isolated from spoiled books in Brazil. Two initial selections were performed, one employing the esculin gel diffusion assay, and the other by culturing on agar plate media with beechwood xylan and liquor from the hydrothermal pretreatment of sugar cane bagasse. A total of 56 isolates were then grown at 29°C on steam-exploded delignified sugar cane bagasse (DEB) plus soybean bran (SB) (3:1), with measurement of the xylanase, pectinase, β-glucosidase, CMCase, and FPase activities. Twelve strains were selected, and their enzyme extracts were assessed using different substrates. Finally, the best six strains were grown under xylan and pectin, and several glycohydrolases activities were also assessed. These strains were identified morphologically and by sequencing the internal transcribed spacer (ITS) regions and the partial β-tubulin gene (BT2). The best six strains were identified asAspergillus nigerDR02,Trichoderma atrovirideDR17 and DR19,Alternariasp. DR45,Annulohypoxylon stigyumDR47 andTalaromyces wortmanniiDR49. These strains produced glycohydrolases with different profiles, and production was highly influenced by the carbon sources in the media.

Conclusions

The selected endophytic fungiAspergillus nigerDR02,Trichoderma atrovirideDR17 and DR19,Alternariasp. DR45,Annulohypoxylon stigyumDR47 andTalaromyces wortmanniiDR49 are excellent producers of hydrolytic enzymes to be used as part of blends to decompose sugarcane biomass at industrial level.
Rhodiola crenulata extract for prevention of acute mountain sickness: a randomized, double-blind, placebo-controlled, crossover trial
Authors: Chiu Te-Fa , Chen Lisa Li-Chuan , Su Deng-Huang , Lo Hsiang-Yun , Chen Chung-Hsien , Wang Shih-Hao , Chen Wei-Lung
Published: October 2013

Background

Rhodiola crenulata (R. crenulata) is widely used to prevent acute mountain sickness in the Himalayan areas and in Tibet, but no scientific studies have previously examined its effectiveness. We conducted a randomized, double-blind, placebo-controlled crossover study to investigate its efficacy in acute mountain sickness prevention.

Methods

Healthy adult volunteers were randomized to 2 treatment sequences, receiving either 800 mg R. crenulata extract or placebo daily for 7 days before ascent and 2 days during mountaineering, before crossing over to the alternate treatment after a 3-month wash-out period. Participants ascended rapidly from 250 m to 3421 m on two separate occasions: December 2010 and April 2011. The primary outcome measure was the incidence of acute mountain sickness, as defined by a Lake Louise score ≥ 3, with headache and at least one of the symptoms of nausea or vomiting, fatigue, dizziness, or difficulty sleeping.

Results

One hundred and two participants completed the trial. There were no demographic differences between individuals taking Rhodiola-placebo and those taking placebo-Rhodiola. No significant differences in the incidence of acute mountain sickness were found between R. crenulata extract and placebo groups (all 60.8%; adjusted odds ratio (AOR) = 1.02, 95% confidence interval (CI) = 0.69–1.52). The incidence of severe acute mountain sickness in Rhodiola extract vs. placebo groups was 35.3% vs. 29.4% (AOR = 1.42, 95% CI = 0.90–2.25).

Conclusions

R. crenulata extract was not effective in reducing the incidence or severity of acute mountain sickness as compared to placebo.

Trial registration

ClinicalTrials.govNCT01536288.
Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2
Authors: Long Limin , Huang Guoqing , Zhu Hongyi , Guo Yonghong , Liu Youshuo , Huo Jirong
Published: October 2013

Background

Colorectal cancer (CRC) is the most common digestive system malignancy. The molecular events involved in the development and progression of CRC remain unclear. Recently, more and more evidences have showed that deregulated miRNAs participate in colorectal carcinogenesis.

Methods

The expression levels of miR-138 were first examined in CRC cell lines and tumor tissues by real-time PCR. Thein vitroandin vivofunctional effects of miR-138 were examined further. Luciferase reporter assays were conducted to confirm the targeting associations. Kaplan-Meier analysis and log-rank tests were performed to estimate the overall survival and disease free survival rate.

Results

miR-138 was found to be down-regulated in human colorectal cancer tissues and cell lines. Ectopic expression of miR-138 resulted in a dramatic inhibition of CRC migration and invasionin vitroandin vivo. Twist basic helix-loop-helix transcription factor 2 gene (TWIST2) was identified as one of the functional target. Restoration of miR-138 resulted in a dramatic reduction of the expression of TWIST2 at both mRNA and protein levels by directly targeting its 3′-untranslated region (3′UTR). Up-regulation of TWIST2 was detected in CRC tumors compared with adjacent normal tissues (P < 0.001) and is inversely correlated with miR-138 expression. We also identified that down-regulation of miR-138 was associated with lymph node metastasis, distant metastasis, and always predicted poor prognosis.

Conclusion

These data highlight a pivotal role for miR-138 in the regulation of CRC metastasis by targeting TWIST2, and suggest a potential application of miR-138 in prognosis prediction and CRC treatment.
Achievable rates optimization for broadcast channels using finite size constellations under transmission constraints
Authors: Mheich Zeina , Alberge Florence , Duhamel Pierre
Published: October 2013

In this paper, maximal achievable rate regions are derived for power-constrained AWGN broadcast channel involving finite constellations and two users. The achievable rate region is studied for various transmission strategies including superposition coding and compared to standard schemes such as time sharing. The maximal achievable rates are obtained by optimizing over both the joint distribution of probability and over the constellation symbol positions. A numerical solution is proposed for solving this non-convex optimization problem. Then, we consider several variations of the same problem by introducing various constraints on the optimization variables. The aim is to evaluate efficiency vs. complexity tradeoffs of several transmission strategies, some of which (the simplest ones) can be found in actual standards. The improvement for each scheme is evaluated in terms of SNR savings for target achievable rates or/and percentage of gain in achievable rates for one user compared to a reference scheme. As an application, two scenarios of coverage areas and user alphabets are considered. This study allows to evaluate with practical criteria the performance improvement brought by more advanced schemes.
Rationale and study design of ViPS – variable pressure support for weaning from mechanical ventilation: study protocol for an international multicenter randomized controlled open trial
Authors: Kiss Thomas , Güldner Andreas , Bluth Thomas , Uhlig Christopher , Spieth Peter Markus , Markstaller Klaus , Ullrich Roman , Jaber Samir , Santos Jose Alberto , Mancebo Jordi , Camporota Luigi , Beale Richard , Schettino Guilherme , Saddy Felipe , Vallverdú Immaculada , Wiedemann Bärbel , Koch Thea , Schultz Marcus Josephus , Pelosi Paolo , de Abreu Marcelo Gama
Published: October 2013

Background

In pressure support ventilation (PSV), a non-variable level of pressure support is delivered by the ventilator when triggered by the patient. In contrast, variable PSV delivers a level of pressure support that varies in a random fashion, introducing more physiological variability to the respiratory pattern. Experimental studies show that variable PSV improves gas exchange, reduces lung inflammation and the mean pressure support, compared to non-variable PSV. Thus, it can theoretically shorten weaning from the mechanical ventilator.

Methods/design

The ViPS (variable pressure support) trial is an international investigator-initiated multicenter randomized controlled open trial comparing variable vs. non-variable PSV. Adult patients on controlled mechanical ventilation for more than 24 hours who are ready to be weaned are eligible for the study. The randomization sequence is blocked per center and performed using a web-based platform. Patients are randomly assigned to one of the two groups: variable PSV or non-variable PSV. In non-variable PSV, breath-by-breath pressure support is kept constant and targeted to achieve a tidal volume of 6 to 8 ml/kg. In variable PSV, the mean pressure support level over a specific time period is targeted at the same mean tidal volume as non-variable PSV, but individual levels vary randomly breath-by-breath. The primary endpoint of the trial is the time to successful weaning, defined as the time from randomization to successful extubation.

Discussion

ViPS is the first randomized controlled trial investigating whether variable, compared to non-variable PSV, shortens the duration of weaning from mechanical ventilation in a mixed population of critically ill patients. This trial aims to determine the role of variable PSV in the intensive care unit.

Trial registration

clinicaltrials.gov NCT01769053
Expression of the senescence marker p16INK4a in skin biopsies of acute lymphoblastic leukemia survivors: a pilot study
Authors: Marcoux Sophie , Le Oanh NL , Langlois-Pelletier Chloé , Laverdière Caroline , Hatami Afshin , Robaey Philippe , Beauséjour Christian M
Published: October 2013

Background

Most childhood cancer survivors will develop ionizing radiation treatment-related health conditions that, in many instances, resemble age-associated pathologies. Treatment-induced premature senescence could be an underlying mechanism.

Findings

Here we wanted to know whether the expression of p16INK4a, a senescence/aging biomarker, is increased in skin biopsies of acute lymphoblastic leukemia survivors (ALL), previously exposed to chemotherapy and radiation therapy. Several years post-treatments, we found p16INK4a mRNA levels are 5.8 times higher in scalp skin biopsies (targeted by cranial irradiation therapy) compared to buttocks skin biopsies (n = 10, p = 0.01).

Conclusions

These results demonstrate for the first time that premature senescence is induced in pediatric cancer survivors and that p16INK4a expression could be used as a potential biomarker in this population.
Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer
Authors: Rajagopalan Malolan S , Heron Dwight E , Wegner Rodney E , Zeh Herbert J , Bahary Nathan , Krasinskas Alyssa M , Lembersky Barry , Brand Randall , Moser A James , Quinn Annette E , Burton Steven A
Published: October 2013

Background

Neoadjuvant stereotactic body radiotherapy (SBRT) has potential applicability in the management of borderline resectable and locally-advanced pancreatic adenocarcinoma. In this series, we report the pathologic outcomes in the subset of patients who underwent surgery after neoadjuvant SBRT.

Methods

Patients with borderline resectable or locally-advanced pancreatic adenocarcinoma who were treated with SBRT followed by resection were included. Chemotherapy was to the discretion of the medical oncologist and preceded SBRT for most patients.

Results

Twelve patients met inclusion criteria. Most (92%) received neoadjuvant chemotherapy, and gemcitabine/capecitabine was most frequently utilized (n = 7). Most were treated with fractionated SBRT to 36 Gy/3 fractions (n = 7) and the remainder with single fraction to 24 Gy (n = 5). No grade 3+ acute toxicities attributable to SBRT were found. Two patients developed post-surgical vascular complications and one died secondary to this. The mean time to surgery after SBRT was 3.3 months. An R0 resection was performed in 92% of patients (n = 11/12). In 25% (n = 3/12) of patients, a complete pathologic response was achieved, and an additional 16.7% (n = 2/12) demonstrated <10% viable tumor cells. Kaplan-Meier estimated median progression free survival is 27.4 months. Overall survival is 92%, 64% and 51% at 1-, 2-, and 3-years.

Conclusions

This study reports the pathologic response in patients treated with neoadjuvant chemotherapy and SBRT for borderline resectable and locally-advanced pancreatic cancer. In our experience, 92% achieved an R0 resection and 41.7% of patients demonstrated either complete or extensive pathologic response to treatment. The results of a phase II study of this novel approach will be forthcoming.
Changes in parafoveal retinal thickness and subfoveal choroidal thickness in a patient with dengue fever-associated maculopathy
Authors: Yamamoto Kazuhiro , Takahashi Hidenori , Kanno Mikiko , Noda Yasuo , Fujino Yujiro
Published: October 2013

Background

The time courses of retinal and choroidal thickness changes in dengue fever-associated maculopathy are not known. We measured central macular thickness (CMT), parafoveal retinal thickness (PRT), and subfoveal choroidal thickness (SCT), in one case, employing optical coherence tomography.

Findings

The patient was a 43-year-old man diagnosed with dengue fever in Sri Lanka. He became aware of blurred vision bilaterally and visited our department 2 weeks after the onset. He showed reduced visual acuity. The Amsler test revealed a doughnut-shaped relative scotoma. Based on the course of this condition, dengue fever-associated maculopathy was diagnosed. One month later, 20 mg triamcinolone was injected into sub-Tenon space of the left eye. Both eyes showed subsequent improvement. PRT of both eyes increased 1 week after the first visit and decreased thereafter, reaching a plateau 1 month after the first visit. The change in CMT was minimal. SCT changed markedly, with the similar pattern in both eyes, though no particular tendency was noted during the observation period.

Conclusions

Dengue fever-associated maculopathy appears to be closely associated with thickening of the inner layer of the retina, but not with changes in choroidal thickness.
Predictive value of tumor recurrence using urinary vascular endothelial factor levels in patients receiving radiation therapy for Glioblastoma Multiforme (GBM)
Authors: Krauze Andra V , Won Minhee , Graves Christian , Corn Ben W , Muanza Thierry M , Howard Steven P , Mahadevan Arul , Schultz Christopher J , Haas Michael L , Mehta Minesh P , Camphausen Kevin A
Published: October 2013

Background

Glioblastoma Multiforme (GBM) is the most common primary malignant tumor of the central nervous system. Standard of care includes maximal resection followed by chemoradiotherapy. Tumors need adequate perfusion and neovascularization to maintain oxygenation and for removal of wastes. Vascular endothelial growth factor (VEGF) is a well characterized pro-angiogenic factor. We hypothesized that the increases in urinary VEGF levels would occur early in the course of tumor recurrence or progression. We examine the feasibility of collecting and analyzing urinary VEGF levels in a prospective, multi-institutional trial (Radiation Therapy Oncology Group, RTOG, 0611) as well as the role of VEGF as a marker of tumor recurrence.

Method

We evaluated VEGF levels in urine specimens collected post-operatively, at the conclusion of radiation therapy (RT) and one month following RT. Urinary VEGF levels were correlated with tumor progression at one year. VEGF levels were measured by enzyme-linked immunosorbant assay in urine specimens and normalized to urinary creatinine levels. Sample size was determined based on a 50% 1-year recurrence rate. With a sensitivity and specificity of 80%, the expected 95% confidence interval was (0.69, 0.91) with 100 patients. A failure was defined as documented disease progression, recurrence or death before one year.

Results

202 patients were enrolled between February-2006 and October-2007. Four patients were ineligible as they did not receive RT. Of the remaining 198 patients, 128 had all three samples collected. In this group, 35 patients (27.3%) did not progress, 89 (69.5%) had progression and 4 (3.1%) died without evidence of progression. Median VEGF levels at baseline were 52.9 pg/mg Cr (range 0.2- 15,034.4); on the last day of RT, 56.6 (range 0–2,377.1); and at one month follow-up, 70.0 (range 0.1-1813.2). In patients without progression at 1-year, both baseline VEGF level and end of RT VEGF level were lower than those of patients who progressed: 40.3 (range 0.2-350.8) vs. 59.7 (range 1.3-15,034.4) and 41.8 (range 0–356.8) vs. 69.7 (range 0–2,377.1), respectively. This did not reach statistical significance. Comparison of the change in VEGF levels between the end of RT and one month following RT, demonstrated no significant difference in the proportions of progressors or non-progressors at 1-year for either the VEGF increased or VEGF decreased groups.

Conclusion

Urine can be collected and analyzed in a prospective, multi-institutional trial. In this study of patients with GBM a change in urinary VEGF levels between the last day of RT and the one month following RT did not predict for tumor progression by one year.
An optimized five-gene multi-platform predictor of hormone receptor negative and triple negative breast cancer metastatic risk
Authors: Yau Christina , Sninsky John , Kwok Shirley , Wang Alice , Degnim Amy , Ingle James N , Gillett Cheryl , Tutt Andrew , Waldman Fred , Moore Dan , Esserman Laura , Benz Christopher C
Published: October 2013

Introduction

Outcome predictors in use today are prognostic only for hormone receptor-positive (HRpos) breast cancer. Although microarray-derived multigene predictors of hormone receptor-negative (HRneg) and/or triple negative (Tneg) breast cancer recurrence risk are emerging, to date none have been transferred to clinically suitable assay platforms (for example, RT-PCR) or validated against formalin-fixed paraffin-embedded (FFPE) HRneg/Tneg samples.

Methods

Multiplexed RT-PCR was used to assay two microarray-derived HRneg/Tneg prognostic signatures IR-7 and Buck-4) in a pooled FFPE collection of 139 chemotherapy-naïve HRneg breast cancers. The prognostic value of the RT-PCR measured gene signatures were evaluated as continuous and dichotomous variables, and in conditional risk models incorporating clinical parameters. An optimized five-gene index was derived by evaluating gene combinations from both signatures.

Results

RT-PCR measured IR-7 and Buck-4 signatures proved prognostic as continuous variables; and conditional risk modeling chose nodal status, the IR-7 signature, and tumor grade as significant predictors of distant recurrence (DR). From the Buck-4 and IR-7 signatures, an optimized five-gene (TNFRSF17, CLIC5, HLA-F, CXCL13, XCL2) predictor was generated, referred to as the Integrated Cytokine Score (ICS) based on its functional pathway linkage through interferon-γ and IL-10. Across all FFPE cases, the ICS was prognostic as either a continuous or dichotomous variable, and conditional risk modeling selected nodal status and ICS as DR predictors. Further dichotomization of node-negative/ICS-low FFPE cases identified a subset of low-grade HRneg tumors with <10% 5-year DR risk. The prognostic value of ICS was reaffirmed in two previously studied microarray assayed cohorts containing 274 node-negative and chemotherapy naive HRneg breast cancers, including 95 Tneg cases where it proved prognostically independent of Tneg molecular subtyping. In additional HRneg/Tneg microarray assayed cohorts, the five-gene ICS also proved prognostic irrespective of primary tumor nodal status and adjuvant chemotherapy intervention.

Conclusion

We advanced the measurement of two previously reported microarray-derived HRneg/Tneg breast cancer prognostic signatures for use in FFPE samples, and derived an optimized five-gene Integrated Cytokine Score (ICS) with multi-platform capability of predicting metastatic outcome from primary HRneg/Tneg tumors independent of nodal status, adjuvant chemotherapy use, and Tneg molecular subtype.
Better lactate clearance associated with good neurologic outcome in survivors who treated with therapeutic hypothermia after out-of-hospital cardiac arrest
Authors: Lee Tae Rim , Kang Mun Ju , Cha Won Chul , Shin Tae Gun , Sim Min Seob , Jo Ik Joon , Song Keun Jeong , Jeong Yeon Kwon , Cho Jun Hwi
Published: October 2013

Introduction

Several methods have been proposed to evaluate neurological outcome in out-of-hospital cardiac arrest (OHCA) patients. Blood lactate has been recognized as a reliable prognostic marker for trauma, sepsis, or cardiac arrest. The objective of this study was to examine the association between initial lactate level or lactate clearance and neurologic outcome in OHCA survivors who were treated with therapeutic hypothermia.

Methods

This retrospective cohort study included patients who underwent protocol-based 24-hour therapeutic hypothermia after OHCA between January 2010 and March 2012. Serum lactate levels were measured at the start of therapy (0 hours), and after 6 hours, 12 hours, 24 hours, 48 hours and 72 hours. The 6 hour and 12 hour lactate clearance were calculated afterwards. Patients’ neurologic outcome was assessed at one month after cardiac arrest; good neurological outcome was defined as Cerebral Performance Category one or two. The primary outcome was an association between initial lactate level and good neurologic outcome. The secondary outcome was an association between lactate clearance and good neurologic outcome in patients with initial lactate level >2.5 mmol/l.

Results

Out of the 76 patients enrolled, 34 (44.7%) had a good neurologic outcome. The initial lactate level showed no significant difference between good and poor neurologic outcome groups (6.07 ±4 .09 mmol/L vs 7.13 ± 3.99 mmol/L, P = 0.42), However, lactate levels at 6 hours, 12 hours, 24 hours, and 48 hours in the good neurologic outcome group were lower than in the poor neurologic outcome group (3.81 ± 2.81 vs 6.00 ± 3.22 P <0.01, 2.95 ± 2.07 vs 5.00 ± 3.49 P <0.01, 2.17 ± 1.24 vs 3.86 ± 3.92 P <0.01, 1.57 ± 1.02 vs 2.21 ± 1.35 P = 0.03, respectively). The secondary analysis showed that the 6-hour and 12-hour lactate clearance was higher for good neurologic outcome patients (35.3 ± 34.6% vs 6.89 ± 47.4% P = 0.01, 54.5 ± 23.7% vs 25.6 ± 43.7% P <0.01, respectively). After adjusting for potential confounding variables, the 12-hour lactate clearance still showed a statistically significant difference (P = 0.02).

Conclusion

The lactate clearance rate, and not the initial lactate level, was associated with neurological outcome in OHCA patients after therapeutic hypothermia.
High fat feeding promotes obesity and renal inflammation and protects against post cardiopulmonary bypass acute kidney injury in swine
Authors: Sleeman Philippa , Patel Nishith N , Lin Hua , Walkden Graham J , Ray Paramita , Welsh Gavin I , Satchell Simon C , Murphy Gavin J
Published: October 2013

Introduction

Obesity confers a survival advantage in the critically ill and in patients undergoing cardiac surgery. We explored whether an obesogenic high fat diet could confer protection against post cardiopulmonary bypass (CPB) acute kidney injury (AKI) in a swine model.

Methods

In this study, 28 anaesthetised adult female Landrace White swine (55 to 70 kg) were allocated into a 4 group design to either 2.5 hours of CPB or Sham operation with or without pre-procedural high fat (HF) feeding containing 15% lard, 1.5% cholesterol and 1% cholic acid for 12-weeks (Groups: Sham, CPB, CPB + HF and Sham + HF). Our primary endpoint was creatinine clearance measured at 1.5 and 24 hours post intervention. This is a validated index of the glomerular filtration rate (GFR) in swine and an endpoint used in our clinical studies. Secondary endpoints included measures of systemic and renal inflammation, endothelial homeostasis, tubular injury and dysfunction, and inflammatory cell signalling. Differences between groups were calculated using analysis of variance with adjustment for baseline differences for repeated measures.

Results

CPB in pigs fed a normal chow diet resulted in AKI. This was characterised by reductions in GFR sustained for up to 24 hours post injury relative to Sham operated pigs fed a normal diet; mean difference 50.2 ml/min (95% CI 5.9 to 94.4). Post CPB AKI was also characterised by renal inflammation, parallel activation of both pro-inflammatory (NF-kB, iNOS) and pro-survival pathways (pAkt, p70s6k, HIF-1α) and apoptosis. Pigs fed a 12-week high fat diet developed obesity and hyperlipidaemia. This was associated with increased redox sensitive pro-inflammatory and anti-apoptotic signalling, and tubular epithelial cell proliferation. High fat feeding also protected swine against post CPB AKI; mean difference in creatinine clearance CPB - CPB + HF −65.3 ml/min (95% CI −106.9 to −23.7), by preserving endothelial homeostasis and function, and preventing the reductions in GFR, loss of ATP and tubular apoptosis that characterise the extension phase of AKI in swine at 24 hours post injury. Reno-protection was not attributed to pAkt signaling.

Conclusions

A high fat diet promoted obesity and renal inflammation and prevented post CPB AKI in swine. This study provides insights into the obesity paradox and the failure of anti-inflammatory interventions to improve clinical outcomes in patients at risk of post cardiac surgery AKI.
Variation of Source-to-Site Distance for Megathrust Subduction Earthquakes: Effects on Ground Motion Prediction Equations
Authors: Goda Katsuichiro , Atkinson Gail M.
Published: October 2013

This study investigates the effects of using different finite-fault source models in evaluating rupture distances for megathrust subduction earthquakes. The uncertainty of the calculated rupture distances affects interpretation of the recorded ground motions significantly. To demonstrate this from an empirical perspective, ground motion data and available finite-fault models for the 2011 M9.0 Tohoku, 2003 M8.3 Tokachi-oki, and 2005 M7.2 Miyagi-oki earthquakes are analyzed. The impact of different finite-fault models on the development of ground motion prediction equations for these large subduction events is significant. Importantly, the results suggest that comparison of observed ground motion data with existing ground motion prediction models is not straightforward; different conclusions may be reached regarding agreement/disagreement between empirical data and developed models, depending on the selected finite-fault model. These results are particularly relevant to the development of ground motion prediction equations for subduction regions.
Intraslab versus Interplate Earthquakes as Recorded in Mexico City: Implications for Seismic Hazard
Authors: Singh Shri K. , Ordaz Mario , Pérez-Campos Xyoli , Iglesias Arturo
Published: October 2013

We study the relative importance of interplate and intraslab earthquakes in the seismic hazard of Mexico City by analyzing accelerograms recorded at the hill-zone site of CU (1964–2012) and the lake-bed site of SCT (1985–2012). Amax exceeded 6 gal during 20 earthquakes at CU during this period. Of these, eight were intraslab events so that the exceedance rate of Amax ≥ 6 gal from both types of earthquakes is roughly about the same. The estimated return period of Amax of 30 gal from the two types of earthquakes is ∼100 yrs. If we consider high-frequency (2.5–8.5 Hz) acceleration ( AmaxHF) at CU, then the top 7 out of the 20 events are all intraslab earthquakes. Even at the lake-bed site of SCT, the AmaxHF values are, generally, associated with intraslab earthquakes. It follows that the risk from both types of earthquakes to low-rise construction in the city needs careful assessment.
A dual to tight closure theory
Authors: Epstein Neil , Schwede Karl
Published: October 2013

We introduce an operation on modules over anF-finite ring of characteristicp. We call this operationtight interior. While it exists more generally, in some cases this operation is equivalent to the Matlis dual of tight closure. Moreover, the interior of the ring itself is simply the big test ideal. We directly prove, without appeal to tight closure, results analogous to persistence, colon capturing, and working modulo minimal primes, and we begin to develop a theory dual to phantom homology. Using our dual notion of persistence, we obtain new and interesting transformation rules for tight interiors, and so in particular for the test ideal. Using our theory of phantom homology, we prove a vanishing theorem for maps of Ext. We also compare our theory with Blickle’s notion of Cartier modules, and in the process we prove new existence results for Blickle’s test submodule. Finally, we apply the theory we developed to the study of test ideals in nonnormal rings, proving that the finitistic test ideal coincides with the big test ideal in some cases.
Growth differentiation factor 5 is a key physiological regulator of dendrite growth during development
Authors: Osório Catarina , Chacón Pedro J. , Kisiswa Lilian , White Matthew , Wyatt Sean , Rodríguez-Tébar Alfredo , Davies Alun M.
Published: October 2013

Dendrite size and morphology are key determinants of the functional properties of neurons. Here, we show that growth differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) subclass of the transforming growth factor β superfamily with a well-characterised role in limb morphogenesis, is a key regulator of the growth and elaboration of pyramidal cell dendrites in the developing hippocampus. Pyramidal cells co-express GDF5 and its preferred receptors, BMP receptor 1B and BMP receptor 2, during development. In culture, GDF5 substantially increased dendrite, but not axon, elongation from these neurons by a mechanism that depends on activation of SMADs 1/5/8 and upregulation of the transcription factor HES5. In vivo, the apical and basal dendritic arbours of pyramidal cells throughout the hippocampus were markedly stunted in both homozygous and heterozygous Gdf5 null mutants, indicating that dendrite size and complexity are exquisitely sensitive to the level of endogenous GDF5 synthesis.
Experimental verification of dynamic soaring in albatrosses
Authors: Sachs G. , Traugott J. , Nesterova A. P. , Bonadonna F.
Published: October 2013

Dynamic soaring is a small-scale flight manoeuvre which is the basis for the extreme flight performance of albatrosses and other large seabirds to travel huge distances in sustained non-flapping flight. As experimental data with sufficient resolution of th ese small-scale movements are not available, knowledge is lacking about dynamic soaring and the physical mechanism of the energy gain of the bird from the wind. With new in-house developments of GPS logging units for recording raw phase observations and of a dedicated mathematical method for postprocessing these measurements, it was possible to determine the small-scale flight manoeuvre with the required high precision. Experimental results from tracking 16 wandering albatrosses (Diomedea exulans) in the southern Indian Ocean show the characteristic pattern of dynamic soaring. This pattern consists of four flight phases comprising a windward climb, an upper curve, a leeward descent and a lower curve, which are continually repeated. It is shown that the primary energy gain from the shear wind is attained in the upper curve where the bird changes the flight direction from windward to leeward. As a result, the upper curve is the characteristic flight phase of dynamic soaring for achieving the energy gain necessary for sustained non-flapping flight.
Hemoglobin function and allosteric regulation in semi-fossorial rodents (family Sciuridae) with different altitudinal ranges
Authors: Revsbech Inge G. , Tufts Danielle M. , Projecto-Garcia Joana , Moriyama Hideaki , Weber Roy E. , Storz Jay F. , Fago Angela
Published: October 2013

Semi-fossorial ground squirrels face challenges to respiratory gas transport associated with the chronic hypoxia and hypercapnia of underground burrows, and such challenges are compounded in species that are native to high altitude. During hibernation, such species must also contend with vicissitudes of blood gas concentrations and plasma pH caused by episodic breathing. Here, we report an analysis of hemoglobin (Hb) function in six species of marmotine ground squirrels with different altitudinal distributions. Regardless of their native altitude, all species have high Hb–O2 affinities, mainly due to suppressed sensitivities to allosteric effectors [2,3-diphosphoglycerate (DPG) and chloride ions]. This suppressed anion sensitivity is surprising given that all canonical anion-binding sites are conserved. Two sciurid species, the golden-mantled and thirteen-lined ground squirrel, have Hb–O2 affinities that are characterized by high pH sensitivity and low thermal sensitivity relative to the Hbs of humans and other mammals. The pronounced Bohr effect is surprising in light of highly unusual amino acid substitutions at the C-termini that are known to abolish the Bohr effect in human HbA. Taken together, the high O2 affinity of sciurid Hbs suggests an enhanced capacity for pulmonary O2 loading under hypoxic and hypercapnic conditions, while the large Bohr effect should help to ensure efficient O2 unloading in tissue capillaries. In spite of the relatively low thermal sensitivities of the sciurid Hbs, our results indicate that the effect of hypothermia on Hb oxygenation is the main factor contributing to the increased blood–O2 affinity in hibernating ground squirrels.
Possible age-related hearing loss (presbycusis) and corresponding change in echolocation parameters in a stranded Indo-Pacific humpback dolphin
Authors: Li Songhai , Wang Ding , Wang Kexiong , Hoffmann-Kuhnt Matthias , Fernando Nimal , Taylor Elizabeth A. , Lin Wenzhi , Chen Jialin , Ng Timothy
Published: October 2013

The hearing and echolocation clicks of a stranded Indo-Pacific humpback dolphin (Sousa chinensis) in Zhuhai, China, were studied. This animal had been repeatedly observed in the wild before it was stranded and its age was estimated to be ~40 years. The animal's hearing was measured using a non-invasive auditory evoked potential (AEP) method. Echolocation clicks produced by the dolphin were recorded when the animal was freely swimming in a 7.5 m (width)×22 m (length)×4.8 m (structural depth) pool with a water depth of ~2.5 m. The hearing and echolocation clicks of the studied dolphin were compared with those of a conspecific younger individual, ~13 years of age. The results suggested that the cut-off frequency of the high-frequency hearing of the studied dolphin was ~30–40 kHz lower than that of the younger individual. The peak and centre frequencies of the clicks produced by the older dolphin were ~16 kHz lower than those of the clicks produced by the younger animal. Considering that the older dolphin was ~40 years old, its lower high-frequency hearing range with lower click peak and centre frequencies could probably be explained by age-related hearing loss (presbycusis).
Solid-State Photoluminescence Modulation of trans-Alkoxy-Nitrostilbene Dyes by Triggering the Solidification of Mesophases via External Stimuli
Authors: Chen Chien-Chih , Hinoue Tomoaki , Liu Jui-Hsiang , Hisaki Ichiro , Miyata Mikiji , Tohnai Norimitsu
Published: October 2013

Stimuli-responsive luminescent materials in solid state have many useful applications such as optical recording. However, reversible solid–solid phase transitions are not easy due to the restricted movements of molecules. In order to modulate solid-state emission properties via external stimuli, we aimed to induce various crystallization processes from the liquid-crystalline states of trans-alkoxy-nitrostilbene dyes. The structure–property relationships in the crystalline and liquid-crystalline states of the nitrostilbenes were studied by differential scanning calorimetry (DSC), polarizing optical microscopy (POM), powder X-ray diffraction (PXRD), single-crystal X-ray diffraction (SCD), and photoluminescence spectroscopy (PL). Three types of slipped-stacking structures, which display distinct luminescent intensities, were found in their crystalline state. The photoluminescence color of these dyes in the crystalline state changes from green to yellow depending on the length of their substituted alkyl chains. Various external stimuli, including heat, mechanical force, and ultrasound, were applied to the liquid-crystalline state at supercooled temperatures to trigger different crystallization processes. Accordingly, a number of polymorphs were obtained that displayed various luminescent properties. Among these solids, enhanced luminescence of trans-4-undecyloxy-4′-nitrostilbene (NS11) was obtained through packing changes caused by mechanical force and ultrasonication. The reversible fluorescent properties can be applied to fluorescent recording and sensing.
Superstar Cities
Authors: Gyourko Joseph , Mayer Christopher , Sinai Todd
Published: October 2013

We document large long-run differences in average house price appreciation across metropolitan areas over the past 50 years, and show they can be explained by an inelastic supply of land in some unique locations combined with an increasing number of highincome households nationally. The resulting high house prices and price-to-rent ratios in those “superstar” areas crowd out lower income households. The same forces generate a similar pattern among municipalities within a metropolitan area. These facts suggest that disparate local house price and income trends can be driven by aggregate demand, not just changes in local factors such as productivity or amenities. (JEL R11, R23, R31, R52)
State Gun Policy and Cross-State Externalities: Evidence from Crime Gun Tracing
Authors: Knight Brian
Published: October 2013

This paper provides a theoretical and empirical analysis of cross-state externalities associated with gun regulations that impact gun trafficking. Using tracing data, which identify the source state for crime guns recovered in destination states, we find that firearms tend to flow from states with weak laws to states with strict laws, satisfying a key theoretical condition for the existence of externalities. We also find that gun flows are more significant between nearby states, suggesting that externalities are spatial in nature. Finally, we present evidence that criminal possession of guns is higher in states exposed to weak laws in nearby states. (JEL H76, K14, K42)
Bank Bailouts, International Linkages, and Cooperation
Authors: Niepmann Friederike , Schmidt-Eisenlohr Tim
Published: October 2013

Financial institutions are increasingly linked internationally. As a result, financial crises and government intervention have stronger effects beyond borders. We provide a model of international contagion allowing for bank bailouts. While a social planner trades off tax distortions, liquidation losses, and intra- and intercountry income inequality, in the noncooperative game between governments there are inefficiencies due to externalities, a lack of burden sharing, and free riding. We show that, in absence of cooperation, stronger interbank linkages make government interests diverge, whereas cross-border asset holdings tend to align them. We analyze different forms of cooperation and their effects on global and national welfare. (JEL C72, G01, G21, G28)
Tame Fréchet submanifolds of co-Banach type
Authors: Freyn Walter D.
Published: October 2013

We introduce a new class of submanifolds of co-Banach type in tame Fréchet manifolds and construct tame Fréchet submanifolds as inverse images of regular values of certain tame maps. Our method furnishes an easy way to construct tame Fréchet manifolds. The results presented are key ingredients in the construction of affine Kac–Moody symmetric spaces; they have also important applications in the study of isoparametric submanifolds in tame Fréchet spaces.
Character degree sums of finite groups
Authors: Maróti Attila , Nguyen Hung Ngoc
Published: October 2013

We present some results on
character degree sums in connection with several important
characteristics of finite groups such as p-solvability,
solvability, supersolvability, and nilpotency. Some of them
strengthen known results in the literature.
Isomorphism versus commensurability for a class of finitely presented groups
Authors: Arzhantseva Goulnara , Lafont Jean-François , Minasyan Ashot
Published: October 2013

We construct a class of finitely presented groups within which the
isomorphism problem is solvable but the commensurability
problem is unsolvable. Conversely,
we construct a class of finitely presented
groups within which the commensurability problem is solvable but the isomorphism problem is unsolvable.
These are the first examples of such a contrastive
complexity behavior with respect to the isomorphism problem.
Taiwan’s Wealth Gap and the Evolution of Electoral Politics after the 2008 Global Financial Crisis
Authors: Zheng Zhenqing
Published: October 2013

Taiwan’s economic downturn and wealth gap, under the impact of the 2008 global financial crisis, spurred livelihood/redistributive questions to become electoral issues. This paper explores the linkage between the wealth gap and electoral campaigns, and points to a new political economy trend in today’s Taiwan: class mobilization has become the new driver of party politics, with identity mobilization played down.