bluuebunny/crossref_metadata_2025 huggingface dataset:
Crossed-Screws Provide Greater Tarsometatarsal Fusion Stability Compared to Compression Plates
Authors: Baxter Josh R. , Mani Sriniwasan B. , Chan Jeremy Y. , Vulcano Ettore , Ellis Scott J.
Published: July 2014

Background. Hallux valgus is a common deformity that is often treated with a fusion of the first tarsometatarsal (TMT) joint. Crossed-screws are currently the accepted standard but advances in plate systems present opportunities for improved clinical outcomes; however, in vitro testing should be performed prior to clinical implementation. The purpose of this study was to determine whether a locking plate with surgeon-mediated compression provides similar fusion stability compared to crossed-screws and if bone density or joint size are related to construct success. Methods. Ten matched-pair cadaveric specimens received first TMT fusions with either crossed-screws or a compression plate and were loaded for 1000 cycles to assess the amount of joint motion measured as plantar gapping. Bone density was quantified using computed tomography images of each specimen, and joint height was measured with calipers. Results. Crossed-screws provided 3 times greater resistance to plantar gapping compared to compression plates after 1000 cycles. Bone density and joint size did not affect resistance to plantar gapping for either construct. Conclusion. Lag screws or a plantarly applied plate are needed to maximize TMT fusion stability prior to osseous union. Dorsomedially applied plates are also effective when paired with a lag screw placed across the TMT joint. These constructs do not appear to depend on bone density or joint size, suggesting that patients with osteoporosis are viable candidates. Clinical Relevance. The results of this study suggest that traditional, lagged cross-screws provide greater stability to that of a dorsally place compression plate and may lead to better rates of union.

Levels of Evidence: Therapeutic, Level V: Cadaveric Study
Human Milk Analysis Contributes to Nutritional Management of Very Low Birth Weight Infants
Authors: Sparks Blake B. , Radmacher Paula G. , Lewis Salisa L. , Serke Laura A. , Adamkin David H.
Published: July 2014

Objective. To evaluate the contribution of real-time human milk (HM) analysis in the development of individual fortification plans for very low birth weight (VLBW) infants (<1500 g). Methods. Pooled, 24-hour samples of HM were analyzed 1 to 2 times weekly. HM was fortified using 30 kcal/oz preterm formula (PTF) or acidified concentrated liquid formula (ACLF). Daily nutrient intakes, growth, and laboratory data were collected from the week prior to fortification and for the 4 weeks of the study period. Protein (g/kg/day) and energy (kcal/kg/day) intakes were calculated by adding the proportional contributions from HM and fortifier. Results. There were 24 VLBW infants. Both groups (PTF, n = 18; ACLF, n = 6) had similar birth characteristics. HM protein and energy content varied considerably throughout the study. Mean protein intake was significantly higher in infants receiving ACLF (P < 0.001) compared to PTF, while energy intake was similar. The proportion of HM used with ACLF was significantly higher than with PTF (P < 0.001). Mean blood urea nitrogen decreased by about half from prefortifier to week 1 in both groups, although levels were lower in PTF than ACLF infants. Conclusion. Real-time HM analysis and individualized fortification strategies are an effective means of improving protein and energy intakes in VLBW infants.
Big Data in the 1800s in surgical science: A social history of early large data set development in urologic surgery in Paris and Glasgow
Authors: Mazur Dennis J
Published: July 2014

“Big Data” in health and medicine in the 21st century differs from “Big Data” used in health and medicine in the 1700s and 1800s. However, the old data sets share one key component: large numbers. The term “Big Data” is not synonymous with large numbers. Large numbers are a key component of Big Data in health and medicine, both for understanding the full range of how a disease presents in a human for diagnosis, and for understanding if one treatment of a disease is better than another treatment or better than just leaving the patient on his or her own without therapy. In this paper, we examine the first considerations of Big Data in medicine in Paris in the early 1800s when urologic surgeon Jean Civiale collected the first large numbers. Civiale collected the large numbers to defend the efficacy of his urologic instrument, the lithotrite, and the surgical procedure he developed, lithotrity, for the removal of bladder stones compared with earlier, more invasive surgical approaches. We examine how large numbers were adjudicated in social decision-making in the Académie des sciences, Paris, when a dispute arose among French urologic surgeons about the importance of large numbers in surgical science. After Civiale’s successful defense of his instrument and procedure in Paris, we examine how his approach to Big Data (large numbers) impacted data collection by George Buchanan in his use of the procedure at the Royal Hospital Infirmary in Glasgow.
Hering’s Law Assessment Tool Revisited
Authors: Saha Subhranil , Koley Munmun , Arya Jogendra Singh , Choubey Gurudev , Ghosh Shubhamoy , Ganguly Subhasish , Gosavi Tejas , Ghosh Aloke , Ali Syed Afsar , Gupta Neeraj
Published: July 2014

Hering’s Law Assessment Tool emerged as a systematic outcome assessment tool following homeopathic intervention. The authors intend to modify it and develop a new tool—Patient Response Assessment Tool after Homeopathic Treatment (PRATHoT)—in chronic cases through Delphi technique for systematic categorization of probable outcomes following individualized homeopathic treatment in chronic cases. The PRATHoT was drafted after literature review and iterative Delphi rounds with multidisciplinary expert panel, setting Fleiss κ of 0.41 to 1.00 a priori as the desired level of multirater agreement. Following pilot testing, the tool was implemented on 37 patients suffering from knee osteoarthritis over 6 months. Logistic regression analysis confirmed that higher PRATHoT score was significantly associated with achieving pain visual analogue scale responses from the second follow-up visit onwards ( B = 0.037-0.066; SE = 0.021-0.036; P = .003-.048). The tool appeared to have acceptable psychometric properties; hence, it may be considered as a promising tool, amendable for further development.
Mindfulness-Based Stress Reduction as a Stress Management Intervention for Healthy Individuals
Authors: Sharma Manoj , Rush Sarah E.
Published: July 2014

Stress is a global public health problem with several negative health consequences, including anxiety, depression, cardiovascular disease, and suicide. Mindfulness-based stress reduction offers an effective way of reducing stress by combining mindfulness meditation and yoga in an 8-week training program. The purpose of this study was to look at studies from January 2009 to January 2014 and examine whether mindfulness-based stress reduction is a potentially viable method for managing stress. A systematic search from Medline, CINAHL, and Alt HealthWatch databases was conducted for all types of quantitative articles involving mindfulness-based stress reduction. A total of 17 articles met the inclusion criteria. Of the 17 studies, 16 demonstrated positive changes in psychological or physiological outcomes related to anxiety and/or stress. Despite the limitations of not all studies using randomized controlled design, having smaller sample sizes, and having different outcomes, mindfulness-based stress reduction appears to be a promising modality for stress management.
The Lived Experience of Teen Girls’ Abortion in Taiwan
Authors: Lee Tsorng-Yeh , Chou Cheng-Chen , Chen Chin-Mi , Weng Min-Hsueh , Liu Yin-Chun
Published: July 2014

In-depth interviews about the experience after having an abortion were conducted with 20 teenage girls in Taiwan. Six themes emerged by using Colaizzi’s phenomenological methodology: (a) returning to “normal” life as soon as possible, (b) seeking abortion resources, (c) neglecting post-abortion care, (d) disturbed by the fetus ghost, (e) concern about virginity loss and choices for future, and (f) re-examining relationships with partners. Teenage girls received tremendous social and moral pressure due to their traditional cultural and social environment when they went through the abortion experience. The study helps health professionals understand the experience of those girls.
Assessing the Scientific Research Productivity of the Palestinian Higher Education Institutions
Authors: Sweileh Waleed M. , Zyoud Sa’ed H. , Al-Khalil Suleiman , Al-Jabi Samah W. , Sawalha Ansam F.
Published: July 2014

An-Najah National University (ANNU) is a Palestinian university that was established more than 35 years ago. The objective of this study was to do a bibliometric assessment of research output, which describes the growth, contribution, and impact of research carried out by the faculty members, researchers, or students of ANNU in the past 35 years. The data used for this study were retrieved from Scopus database. Bibliometric analysis was used to identify the pattern of publication, relative growth rate, authorship pattern, collaborative measures, author’s productivity, most prolific authors, and most prolific journals. A total of 791 published documents were retrieved for ANNU. Seventeen documents (2.1%) were published in Acta Crystallographica Section E Structure Reports Online, whereas 16 (2.0%) were published in Journal of Environmental Science and Health, Part A: Environmental Science and Engineering, and 10 (1.3%) were published in International Journal of Clinical Pharmacology and Therapeutics. Six hundred one (76%) documents were published in journals listed in Web of Knowledge. The total number of citations for documents published from ANNU, at the time of data analysis (November 19, 2013), was 4,553, with an average of 5.8 citations per document. The study identified 384 (25.8%) documents with 59 countries as ANNU–foreign collaborators. Research output from ANNU showed steady growth over the past 35 years. Research output was high from certain scientific disciplines, whereas was lagging from others. Future emphasis on joint research, international collaboration, and publishing in indexed journals is needed.
Work–Life Interventions
Authors: Ong He Lu Calvin , Jeyaraj Senthu
Published: July 2014

Despite disparities in the conceptualization of work–life balance (WLB) and work–life harmony (WLH) in the literature, there remains no evidence till date to validate these differences. Furthermore, there are currently no insights that shed light on the relationship between work–life initiatives and key business strategies of contemporary organizations. Hence, the current study investigated the differences between the constructs of WLB and WLH using a cognitive dissonance approach and assessed the impact of work–life interventions, based on these approaches, on individual creativity at work. Hundred participants, age ranging from 18 to 32 years ( M = 23.94, SD = 3.87), with at least 6 months of working experience were recruited. Using an online questionnaire, participants were randomly assigned into WLB ( n = 55) or WLH ( n = 45) conditions. Participants were tasked to complete pre- and post-intervention measures of individual creativity, as well as a manipulation check using a cognitive dissonance scale. Results showed that participants in the WLB condition elicit higher levels of cognitive dissonance compared with participants in the WLH condition. This indicates an implicit difference in the constructs of WLB and harmony. Second, findings also suggest that work–life interventions adopting a WLH approach will have a more positive impact on individuals’ creativity at work compared with interventions targeted at achieving balance. Research, practical, and cultural implications of the findings are discussed in the article.
Dolutegravir
Authors: Mercadel Candice J. , Skelley Jessica W. , Kyle Jeffrey A. , Elmore Lindsey K.
Published: July 2014

Objective: To review the efficacy, safety, pharmacokinetics, pharmacodynamics, administration, drug interactions, and cost of dolutegravir (Tivicay), a third in class integrase strand transfer inhibitor (INSTI), for the treatment of human immunodeficiency virus (HIV-1) in adults. Data Sources: MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google Scholar searches (January 2000 to May 2014) were conducted for articles published in English and limited to human subjects, using the key words antiretroviral drugs, HIV integrase strand transfer inhibitors, dolutegravir, DTG, and S/GSK1349572. Study Selection and Data Extraction: Following MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google Scholar searches, 6 clinical trials were identified and included in this review. Phase III/IV studies evaluating the safety and efficacy of dolutegravir in humans were selected and evaluated. Data Synthesis: In treatment naïve and experienced patients dolutegravir was noninferior to raltegravir at suppressing viral load when added to background therapy. Abacavir/lamivudine/dolutegravir was noninferior to efavirenz/emtricitabine/tenofovir disoproxil fumarate and darunavir/ritonavir plus background therapy at suppressing viral load. In patients with multiple-class antiretroviral resistance at baseline, dolutegravir decreased HIV RNA by 1.4 log10 copies/mL at day 8, 63% of patients had achieved virologic suppression at week 8, and retained potency in treatment-experienced INSTI-resistant patients up to week 48 or 96 of follow-up. Conclusion: Dolutegravir is a safe, effective, and well-tolerated treatment option for adults with HIV-1, even in the setting of resistance to other antiretrovirals.
Formation of interfacial microstructure in a friction stir welded lap joint between aluminium alloy and stainless steel
Authors: Nishida T. , Ogura T. , Nishida H. , Fujimoto M. , Takahashi M. , Hirose A.
Published: July 2014

The interfacial microstructure produced through tool transit of a friction stir welded lap joint between an aluminium alloy and stainless steel was studied by transmission electron microscopy in order to clarify its early stages of formation. Transmission electron microscopy studies of the bottom surface of the exit hole revealed the presence of several mixed layers of an ultrafine intermetallic compound (IMC) and stainless steel. The joining between dissimilar materials was achieved through a continuous flow of the stirred aluminium alloy into the mixed layers and the resultant growth of the ultrafine IMCs due to the heat induced by the friction between the tool and the specimen. The continuous thin reaction layer finally produced at the interface was found to be stronger than the base aluminium alloy.
Feasibility study of friction stir welding of wood–plastic composites
Authors: Rahbarpour R. , Azdast T. , Rahbarpour H. , Shishavan S. M.
Published: July 2014

In this study, feasibility of friction stir welding of wood–plastic composites is investigated. For this purpose, a special welding tool including a fixed heated shoe called ‘hot shoe’ is designed. Furthermore, rotating and travelling speeds of the pin and shoe temperature are considered as the variable parameters and tensile strength as the mechanical property of welded samples. A 33 full factorial design of experiment and an analysis of variance is performed in this study. Experimental results show that acceptable weld could be obtained using the designed welding tool. Results also reveal that the statistically significant effects of all parameters are at the confidence level of 95%. It is also concluded that the shoe temperature is the most effective parameter.
Structural health monitoring for smart composites using embedded FBG sensor technology
Authors: Lau K-T.
Published: July 2014

Fibre-optic Bragg grating (FBG) sensors have been recognised as one of the smart localised and globalised structural health monitoring devices for many structural applications. A particular interest has been placed on embedding these sensors into advanced composites for in situ manufacturing process monitoring and then, lifetime structural health monitoring (SHM). There is no doubt that the need of maintaining structural integrity of these composites has been increased owing to an increasing use of carbon and glass fibre composites in real life structural and engineering applications. In the public transportation, the structural components of Airbus 350 XWB and Boeing 787 are made by over 50 of composite materials to replace traditional aluminium alloys. Electric vehicles have used lightweight carbon fibre composites as their chassis to overcome the weight penalty from batteries. With the advantages of high specific stiffness to weight ratio and good damping properties of polymer based composites, these composites are also used to reinforce and strengthen civil concrete structures that are located on the earthquake zones. In some critical engineering components, glass fibre composites with embedded shape memory alloy (SMA) wires are used for stiffness and shape controls during marginally operational conditions. Therefore, developing better SHM technologies is an urgent need to ensure the structural integrity and safety of structures. In this paper, FBG sensors for different SHMs are introduced and discussed. The use of the sensors with appropriate design for smart composites with sensing and actuating capacities is also presented.
Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD
Authors: Khoder Ahmad , Sarvaria Anushruti , Alsuliman Abdullah , Chew Claude , Sekine Takuya , Cooper Nichola , Mielke Stephan , de Lavallade Hugues , Muftuoglu Muharrem , Fernandez Curbelo Irina , Liu Enli , Muraro Paolo A. , Alousi Amin , Stringaris Kate , Parmar Simrit , Shah Nina , Shaim Hila , Yvon Eric , Molldrem Jeffrey , Rouce Rayne , Champlin Richard , McNiece Ian , Mauri Claudia , Shpall Elizabeth J. , Rezvani Katayoun
Published: July 2014

Key Points

Human IgM memory B cells possess immunoregulatory properties analogous to transitional B cells. IL-10–producing B cells are deficient in cGVHD.
Two new sequence spaces generated by the composition of m th order generalized difference matrix and lambda matrix
Authors: Bişgin Mustafa Cemil , Sönmez Abdulcabbar
Published: July 2014

In this work, we introduce two sequence spaces

c
0
λ

(

G
m

)

and

c
λ

(

G
m

)

generated by the composition of m th order generalized difference matrix and lambda matrix and define an isomorphism between new sequence spaces and classical sequence spaces. Afterward, we investigate inclusion relations and obtain the Schauder basis of those spaces. Furthermore, we determine their α-, β- and γ-duals. Lastly, we characterize some matrix classes related to those spaces.

MSC:40C05, 40H05, 46B45.
Multi-strip fractional q-integral boundary value problems for nonlinear fractional q-difference equations
Authors: Pongarm Nittaya , Asawasamrit Suphawat , Tariboon Jessada , Ntouyas Sotiris K
Published: July 2014

In this article, we study the existence and uniqueness of solutions for multi-strip fractional q-integral boundary value problems of nonlinear fractional q-difference equations. By using the Banach contraction principle, Krasnoselskii’s fixed point theorem, Leray-Schauder’s nonlinear alternative and Leray-Schauder degree theory some interesting results are obtained. Some examples are presented to illustrate the results.

MSC:34A08, 34B18, 39A13.
A prospective study comparing the efficacy and safety of two sublingual birch allergen preparations
Authors: Klimek Ludger , Sperl Annette , van Twuijver Esther , van Ree Ronald , Kleinjans Huub , Boot Johan Diderik , Pfaar Oliver
Published: July 2014

Background

SUBLIVAC FIX Birch (SUB‐B) is a liquid oral preparation of Betula verrucosa pollen extract for the treatment of allergic rhinitis/rhinoconjuctivitis induced by birch pollen. The major allergen content of SUB‐B and Staloral Birch (Stal‐B) have been shown to be comparable. In order to compare the clinical efficacy and safety of both products, the present study was designed to investigate efficacy of treatment with SUB‐B compared to Stal‐B by means of reduction in allergy symptoms assessed by a titrated nasal provocation test (TNPT) in subjects suffering from IgE mediated allergy complaints triggered by birch pollen.

Methods

A prospective, randomized, open, blinded endpoint (PROBE), controlled, single‐centre study in 74 birch allergic adults was performed. Treatment consisted of either SUB‐B (10,000 AUN/ml) or Stal‐B (initial phase 10 I.R./ml and maintenance phase 300 I.R./ml) for 16–20 weeks at maintenance dose. The primary efficacy outcome was defined by the difference in change of the TNPT‐threshold dose between the two treatment groups at baseline and after completion of treatment. Secondary outcomes included determination of birch pollen specific IgE and IgG levels, safety lab and ECG. During the first 30 days of treatment, subjects were requested to fill out a diary concerning compliance with study medication, occurrence of AEs and the use of concomitant medication.

Results

Analysis of the primary efficacy parameter showed that the percentage of subjects showing a beneficial treatment effect was similar in both treatment groups, 33.3% for SUB‐B vs. 31.4% for Stal‐B in the intention to treat population. Evaluation of the immunologic response, showed that treatment with SUB‐B and Stal‐B induced similar increases (approximately 2 times) in IgE, IgG and IgG4 specific for Bet v 1.

In total, 143 related adverse events (AEs) were reported. The majority of the AEs was of mild intensity. The same pattern of AEs was observed for both products. No clinically relevant changes in other safety parameters, such as safety laboratory parameters, vital signs, physical examination and ECGs were observed.

Conclusion

Taken together, treatment with both products was effective by means of reduction in allergic symptoms during a TNPT. In addition, safety analysis revealed a good tolerability of both SLIT extracts.
The political economy of the disability insurance: theory and evidence of gubernatorial learning
Authors: Iyengar Radha , Mastrobuoni Giovanni
Published: July 2014

The dramatic rise in the disability insurance (DI) rolls in the last 20 years has been the subject of much controversy. While the relationship between DI and labor force participation has been the subject of a growing literature, the mechanism of this transition from employment to DI remains unclear. We hypothesize that one mechanism is the state-level administration of the program which creates a classic principal-agent problem. We analyze the conflict of interests for Disability Determination Services agencies between Social Security Administration (SSA) standards and state gubernatorial political interests interacted with the increased demand for disability insurance as an alternative for low-skilled employment during the period of 1982 to 2013. We find evidence that multi-term governors allow a greater fraction of applicants than do first-term governors, but only up to year 2000, when allowance rates started to decrease over time. We develop a model that illustrates how these differences can be due to the type of monitoring conducted by the SSA. We provide additional evidence supporting this hypothesis analyzing how the effects interact with economic and political constraints.

JEL codes

H55, I18, I38, G22
Clinical course after corticosteroid therapy in IgG4-related aortitis/periaortitis and periarteritis: a retrospective multicenter study
Authors: Mizushima Ichiro , Inoue Dai , Yamamoto Motohisa , Yamada Kazunori , Saeki Takako , Ubara Yoshifumi , Matsui Shoko , Masaki Yasufumi , Wada Takashi , Kasashima Satomi , Harada Kenichi , Takahashi Hiroki , Notohara Kenji , Nakanuma Yasuni , Umehara Hisanori , Yamagishi Masakazu , Kawano Mitsuhiro
Published: July 2014

Introduction

Immunoglobulin G4 (IgG4)–related aortitis/periaortitis and periarteritis are vascular manifestations of IgG4-related disease. In this disease, the affected aneurysmal lesion has been suspected to be at risk of rupture. In this study, we aimed to clarify the clinical course after corticosteroid therapy in IgG4-related aortitis/periaortitis and periarteritis.

Methods

We retrospectively evaluated clinical features, including laboratory data, imaging findings and the course after corticosteroid therapy, in 40 patients diagnosed with IgG4-related aortitis/periaortitis and periarteritis on the basis of periaortic/periarterial radiological findings, satisfaction of the comprehensive diagnostic criteria or each organ-specific diagnostic criteria, and exclusion of other diseases.

Results

The patients were mainly elderly, with an average age of 66.4 years and with a marked male predominance and extensive other organ involvement. Subjective symptoms were scanty, and only a small proportion had elevated serum C-reactive protein levels. The affected aorta/artery were the abdominal aortas or the iliac arteries in most cases. Thirty-six patients were treated with prednisolone, and the periaortic/periarterial lesions improved in most of them during the follow-up period. Two (50.0%) of four patients with luminal dilatation of the affected lesions before corticosteroid therapy had exacerbations of luminal dilatation after therapy, whereas none of the twenty-six patients without it had a new appearance of luminal dilatation after therapy.

Conclusions

The results of this retrospective multicenter study highlight three important points: (1) the possibility of latent existence and progression of periaortic/periarterial lesions, (2) the efficacy of corticosteroid therapy in preventing new aneurysm formation in patients without luminal dilatation of periaortic/periarterial lesions and (3) the possibility that a small proportion of patients may actually develop luminal dilatation of periaortic/periarterial lesions in IgG4-related aortitis/periaortitis and periarteritis. A larger-scale prospective study is required to confirm the efficacy and safety of corticosteroid therapy in patients with versus those without luminal dilatation and to devise a more useful and safe treatment strategy, including administration of other immunosuppressants.
Interest of low-dose hydrocortisone therapy during brain-dead organ donor resuscitation: the CORTICOME study
Authors: Pinsard Michel , Ragot Stéphanie , Mertes Paul Michel , Bleichner Jean Paul , Zitouni Samira , Cook Fabrice , Pierrot Marc , Dube Laurent , Menguy Edgard , Lefèvre Laurent Martin , Escaravage Laurence , Dequin Pierre-François , Vignon Philippe , Pichon Nicolas
Published: July 2014

Introduction

Circulatory failure during brain death organ donor resuscitation is a problem that compromises recovery of organs. Combined administration of steroid, thyroxine and vasopressin has been proposed to optimize the management of brain deceased donors before recovery of organs. However the single administration of hydrocortisone has not been rigorously evaluated in any trial.

Methods

In this prospective multicenter cluster study, 259 subjects were included. Administration of low-dose steroids composed the steroid group (n = 102).

Results

Although there were more patients in the steroid group who received norepinephrine before brain death (80% vs. 66%: P = 0.03), mean dose of vasopressor administered after brain death was significantly lower than in the control group (1.18 ± 0.92 mg/H vs. 1.49 ± 1.29 mg/H: P = 0.03), duration of vasopressor support use was shorter (874 min vs. 1160 min: P < 0.0001) and norepinephrine weaning before aortic clamping was more frequent (33.8% vs. 9.5%: P < 0.0001). Using a survival approach, probability of norepinephrine weaning was significantly different between the two groups (P < 0.0001) with a probability of weaning 4.67 times higher in the steroid group than in the control group (95% CI: 2.30 – 9.49).

Conclusions

Despite no observed benefits of the steroid administration on primary function recovery of transplanted grafts, administration of glucocorticoids should be a part of the resuscitation management of deceased donors with hemodynamic instability.
Experimental and clinical evidences for glucose control in intensive care: is infused glucose the key point for study interpretation?
Authors: Mazeraud Aurélien , Polito Andrea , Annane Djillali
Published: July 2014

Stress-induced hyperglycemia has been considered an adaptive mechanism to stress up to the first intensive insulin therapy trial, which showed a 34% reduction in relative risk of in-hospital mortality when normalizing blood glucose levels. Further trials had conflicting results and, at present, stress-induced hyperglycemia management remains non-consensual. These findings could be explained by discrepancies in trials, notably regarding the approach to treat hyperglycemia: high versus restrictive caloric intake. Stress-induced hyperglycemia is a frequent complication during intensive care unit stay and is associated with a higher mortality. It results from an imbalance between insulin and counter-regulatory hormones, increased neoglucogenesis, and the cytokine-induced insulin-resistant state of tissues. In this review, we summarize detrimental effects of hyperglycemia on organs in the critically ill (peripheric and central nervous, liver, immune system, kidney, and cardiovascular system). Finally, we show clinical and experimental evidence of potential benefits from glucose and insulin administration, notably on metabolism, immunity, and the cardiovascular system.
Autoimmune uveitis: a retrospective analysis of 104 patients from a tertiary reference center
Authors: Prete Marcella , Guerriero Silvana , Dammacco Rosanna , Fatone Maria Celeste , Vacca Angelo , Dammacco Francesco , Racanelli Vito
Published: July 2014

Background

The aim of this study was to identify the main features of a cohort of Caucasian patients with idiopathic (I) and systemic disease-associated (SDA) autoimmune uveitis (AU) who were followed up at a single tertiary reference center. The study consisted of a retrospective analysis of the demographic, clinical, and laboratory features and the response to treatment of 104 patients with AU evaluated between 2004 and 2013, with a median follow-up of 4.8 years. The primary outcome measure was the response to systemic treatment after 24 months of therapy. The data are expressed as the range, percentage, or mean ± standard error. Categorical variables were assessed by Fisher's exact test.

Results

The mean age at diagnosis was 40.1 ± 17.8 years for men and 44.1 ± 15.3 years for women. There was a slight female predominance. Of the 104 patients, 72.1% had I-AU and 27.9% SDA-AU. The most frequent associations were with ankylosing spondyloarthritis, autoimmune thyroiditis, inflammatory bowel diseases, and Behcet's disease. Symptoms at presentation consisted of eye redness and pain (28.8%), decreased visual acuity (25.9%), and floaters (18.3%). Complications included cataracts (24%), retinal neovascularization (16.3%), chorio-retinal scars (10.6%), cystoid macular edema (8.6%), glaucoma/ocular hypertension (7.7%), epiretinal membranes (4.8%), and retinal detachment (3.8%). The prevalence of autoantibodies, mostly antinuclear antibodies, was comparable between the I-AU and SDA-AU groups. Fisher's exact test showed a direct correlation between patients with class I HLA B27, Cw8, B5 (51, 52), B51, or Cw2 and the presence of AU, whereas among patients with class II HLA, only DQ1 was a predisposing factor for AU. The therapeutic spectrum included corticosteroids and immunosuppressive agents, given either alone or in various combinations according to the severity of AU and the extent of the clinical response. Among the immunosuppressive drugs, azathioprine was preferentially used for anterior uveitis, and cyclosporine-A for intermediate and posterior uveitis. An assessment of the patients after 24 months of therapy showed a complete remission in 43.3% and a significant clinical improvement in 26.9%.

Conclusions

At our tertiary reference center, the prevalence in Caucasian patients of I-AU was approximately 2.5-fold higher than that of SDA-AU. Our findings point to the need for a patient-tailored therapeutic approach according to the anatomic site and the severity of AU. Therapy should be prolonged, over a period of months and even up to 1–2 years, in order to achieve stable control of the disease and to prevent severe complications. The outcome of SDA-AU is also influenced by treatment of the underlying systemic disease. Additional controlled trials are needed to assess the efficacy and the long-term safety of both the prescribed therapeutic agents and their combinations.
Association of phosphatase and tensin homolog low and phosphatidylinositol 3-kinase catalytic subunit alpha gene mutations on outcome in human epidermal growth factor receptor 2-positive metastatic breast cancer patients treated with first-line lapatinib plus paclitaxel or paclitaxel alone
Authors: Xu Binghe , Guan Zhongzhen , Shen Zhenzhou , Tong Zhongshen , Jiang Zefei , Yang Junlan , DeSilvio Michelle , Russo Mark , Leigh Meggan , Ellis Catherine
Published: July 2014

Introduction

Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) has been shown to enhance breast cancer cell survival and confer resistance to chemotherapeutic agents. We studied the prognostic and predictive value of PIK3CA mutations and PTEN low in patients receiving paclitaxel alone or in combination with lapatinib.

Methods

Immunohistochemistry and mutation analyses were used to evaluate PTEN and PIK3CA, respectively. Kaplan-Meier analysis with log-rank tests, logistic regression and Cox models were used in analyses of these biomarkers with efficacy endpoints.

Results

In the overall population, PIK3CA mutations were associated with poorer overall survival (OS) (hazard ratio (HR) = 1.87; 95% confidence interval (CI): 1.22, 2.88; P = 0.001). PTEN expression was not associated with OS (P = 0.474). In the PIK3CA wild-type subgroup, lapatinib plus paclitaxel reduced risk of progression compared with paclitaxel alone (HR = 0.44; 95% CI: 0.28, 0.69; P <0.0001); progression-free survival (PFS) was not significantly improved within the PIK3CA mutation subgroup (P = 0.179). In the PTEN low group, OS was improved with addition of lapatinib (P = 0.039). In both PTEN subgroups, addition of lapatinib was associated with improvements in PFS (P <0.050). PIK3CA and PTEN were not predictive of treatment based on interaction tests (P >0.05).

Conclusions

PTEN was neither a significant prognostic nor predictive factor. PIK3CA mutations were an adverse prognostic factor for survival but not predictive for lapatinib benefit.

Trial registration

ClinicalTrials.gov NCT00281658 (registered 23 January 2006)
Nestin positively regulates the Wnt/β-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells
Authors: Zhao Zuowei , Lu Ping , Zhang Hao , Xu Huanming , Gao Ningning , Li Man , Liu Caigang
Published: July 2014

Introduction

We investigated Nestin expression in triple-negative breast cancer and examined how the modulation of Nestin expression affects cell cycle progression, survival, invasion and regulatory signaling in breast cancer stem cells (CSC) in vitro.

Methods

Nestin expression in 150 triple-negative breast cancer specimens were examined by immunohistochemistry. The role of Nestin expression in tumorigenesis was examined by assaying naturally occurring Nestinhigh/Nestinlow CSC from 12 breast cancer tissues, as well as CSC from 26 clinical specimens, where Nestin overexpression and silencing was achieved by genetic manipulation, for their ability to form mammospheres and induce solid tumors. Cell cycle progression, spontaneous apoptosis and invasiveness of Nestin-silenced breast CSC were investigated by flow cytometry and transwell assays. The relative levels of expression of epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathway-related molecules were determined by western blotting.

Results

Nestin expression was significantly associated with poor survival in patients with triple-negative breast cancer (P = 0.01). Nestinhigh breast CSC rapidly formed typical mammospheres in vitro. Nestinhigh, but not Nestinlow CSC, efficiently formed solid tumors in vivo. Nestin silencing induced cell cycle arrest at G2/M (52.03% versus 19.99% in controls) and promoted apoptosis (36.45% versus 8.29% in controls). Nestin silencing also inhibited breast CSC invasiveness, and was associated with significantly upregulated E-cadherin, while N-cadherin, vimentin, a-smooth muscle actin (a-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression was downregulated (P <0.05 for all). Nestin silencing also upregulated Axin, glycogen synthase kinase-3 beta (GSK-3β), adenomatous polyposis coli (APC), and peroxisome proliferator-activated receptor alpha (PPARa), and downregulated β-catenin, c-Myc, cyclin D and MMP-7 expression in CSC. Inhibition of the Wnt/β-catenin pathway mitigated mammosphere formation in Nestinhigh CSC, while inhibition of GSK-3β promoted the mammosphere formation in Nestinlow CSC (P <0.05 for all).

Conclusions

Our data indicates that Nestin positively regulates the proliferation, survival and invasiveness of breast CSC by enhancing Wnt/β-catenin activation.
The influence of tamoxifen on normal mouse mammary gland homeostasis
Authors: Shehata Mona , van Amerongen Renée , Zeeman Amber L , Giraddi Rajshekhar R , Stingl John
Published: July 2014

Introduction

Lineage tracing using inducible genetic labeling has emerged to be a powerful method for interrogating the developmental fate of cells in intact tissues. A common induction mechanism is the use of tamoxifen-dependent Cre recombinase (CreER and CreERT2), but the effects of tamoxifen at doses normally used in lineage-tracing studies on normal adult mammary gland homeostasis are not known.

Methods

We used flow cytometry and immunostaining of intact glands to determine whether varying doses of tamoxifen skew the distribution and the apoptosis and proliferation status of different types of mammary epithelial cells in vivo. We also examined how tamoxifen influences the number of progenitor and mammary repopulating units (MRUs).

Results

Our results indicate that ≥5 mg/25 g body weight of tamoxifen induces a transient increase in cell proliferation and in the number of basal cells in the adult mammary epithelium up to 7 days after tamoxifen administration. However, in the medium term (3 weeks), all doses of tamoxifen ≥1 mg/25 g body weight result in a decrease in the number of basal and EpCAM+CD49b− luminal cells and a decrease in progenitor cell function. Tamoxifen at doses ≥5 mg/25 g body weight induced a transient increase in caspase-3-mediated apoptotic cell death within the mammary epithelium. However, mammary epithelial cell numbers in all subpopulations were restored to their original levels by 8 weeks. No long-lasting effects of tamoxifen on MRU numbers or on pubertal ductal development were observed.

Conclusion

Tamoxifen can skew the distribution of mammary cell types in a dose-dependent manner, and thus caution must be taken when interpreting lineage-tracing studies using high doses of tamoxifen, particularly when short-duration analyses of a quantitative nature are being performed.
Mediterranean and Near East obsidian reference samples to establish artefacts provenance
Authors: Avino Pasquale , Rosada Alberto
Published: July 2014

Background

The commercial obsidian trade played an important role during Neolithic period. Its characteristics favoured the exchange network. In this way the Mediterranean area was fundamental. The availability of significant numbers of obsidian samples has allowed to improve the knowledge about the trade and commercial routes. Obsidian samples from the Mediterranean (Aegean, Flegrean, North Latium, Sicily, Sardinia) and Near East (Anatolia) areas were directly collected on the sites and considered as reference. Almost 30 elements were analyzed by Instrumental Neutron Activation Analysis (INAA).

Results

The approach based on the source discrimination analysis allowed to identify clearly different obsidian deposits, except the reference samples coming from Flegrean and Sicily areas, quite similar for their geochemical origin. The obtained data were used for assigning the provenance of 71 obsidian artefacts found during archaeological excavations in Tuscany. Two different groups were found: 16 artefacts were attributed to Sicily/Flegrean area whereas 55 items seemed to show a provenance from Aegean.

Conclusions

The results are important because they represents a confirmation about the hypothesis of the existence of a large exchange network in the Mediterranean area since 3000 B.C.
Lead heavy metal toxicity induced changes on growth and antioxidative enzymes level in water hyacinths [Eichhornia crassipes (Mart.)]
Authors: Malar Srinivasan , Shivendra Vikram Sahi , JC Favas Paulo , Perumal Venkatachalam
Published: July 2014

Background

Lead (Pb) heavy metal pollution in water bodies is one of the serious problems across the world. This study was designed to find out the effect of Pb toxicity on physiological and biochemical changes in Eichhornia crassipes (water hyacinth) seedlings.

Results

The plant growth was significantly inhibited (50%) at 1000 mg/L Pb concentration. Accumulation of Pb was higher in root than in shoot tissues. The maximum level of Pb accumulation was noticed in roots (5.45%) followed by petiole (2.72%) and leaf tissues (0.66%). Increasing the Pb concentration gradually decreased the chlorophyll content. Intracellular distribution of Pb was also studied using SEM-EDX, where the Pb deposition was observed in both root and leaf tissues. MDA content increased in both the leaf and root tissues up to the 400 mg/L Pb treatment and slightly decreased at higher concentrations. The activity of antioxidative enzymes, such as APX and POX, positively correlated with Pb treatment, while in the case of SOD and CAT enzymes increased up to 800 mg/L treatment and then slightly decreased at higher concentration in both leaf and root tissues.

Conclusions

These results suggest that water hyacinth plants have efficient mechanism to tolerate Pb toxicity, as evidenced by an increased level of antioxidative enzymes. Results clearly indicate that water hyacinth is a feasible plant for hyperaccumulation of heavy metals from polluted wetlands.
Diagnostics of seismic time-lapse effects of sandstones based on laboratory data
Authors: Moyano Bernardo , Johansen Tor Arne , Agersborg Remy Sverre , Spikes Kyle T.
Published: July 2014

We evaluated a viscoelastic modeling of P- and S-wave velocity dispersion, attenuation, pressure, and fluid effects for a set of siliciclastic rock samples. Our analysis used a published laboratory data set of 63 sandstones with a wide range of compositional heterogeneities. We observed a notable correlation between the (velocity and attenuation) pressure sensitivity and the abundance/lack of quartz in the samples. We included compliant pores (low-aspect ratio) proportionally to the content of secondary minerals to account for the differential sensitivity to pressure. The observed velocity and attenuation were well reproduced by the applied viscoelastic modeling. We found that pores of significantly different scale required pore fluid relaxation time constants of proportionally different magnitudes to reproduce the velocity and attenuation measurements. The relaxation time constant of crack-sized pores can be one order of magnitude smaller than the constant of mesopores. Moreover, the velocity dispersion and attenuation signatures revealed that a pore textural model dependent on lithological composition is critical in the prediction of time-lapse fluid and pressure responses.
Order Through Honor: Masculinity and the Use of Temporary Release in a Greek Prison
Authors: Cheliotis Leonidas K.
Published: July 2014

Severe conditions of imprisonment have contributed to a rise in the frequency and seriousness of unrest in Greek prisons over recent decades. Drawing on fieldwork material collected in the largest and most overcrowded prison for men in Greece, this article explores how prison authorities used the prospect of temporary release as a means of incentivizing conformist behavior among prisoners. It is argued that the effectiveness of this seemingly straightforward mechanism was complicated by practical restrictions on the granting of temporary release, thus leading to “behaviorist” efforts on the part of prison authorities to transfer the incentivizing properties of temporary release itself onto praise they extended to prisoners for observing institutional rules and regulations. The content of such praise entailed references to the ideal of a tamed masculinity embodied in the traditional Greek notion of philotimo, or honor, a finding that bolsters the limited body of research on the pacifying potential of masculine identities in carceral settings. While, and at least in part because, the gains made for order through this process have at best been transitory, the broader politico-economic functions of imprisonment have persisted.
The Militarization and Madness of Everyday Life
Authors: Scheper-Hughes Nancy
Published: July 2014

This essay explores the militarization of everyday life in the United States today, following decades of unresolved cycles of wars fought at home (e.g., the war on drugs) and abroad. A “continuum of violence” is established, through which the tactics of war and war crimes gradually seep into domestic civilian life as the new norms. The gross abuses of presumed enemy combatants in Abu Ghraib and Guantánamo Bay come back to haunt us, as war crimes abroad impact behavior at home. The expansion and deformation of US prison culture—isolation, solitary confinement, and other dehumanizing practices—illustrate the militarization of US society. The mimetic recycling of war- and peacetime crimes is complete when the force-feeding of hunger strikers at Guantánamo Bay finds its parallel in the force-feeding of hunger strikers at Pelican Bay prison in California. The normalization of the abnormal and the militarization of everyday life appear in the proliferation of armed and dangerous gated communities, the presence of the invisible de rigueur house gun or house arsenal, invisible surveillance, and civilian passive acquiescence to stop-and-frisk encounters as well as in the mass incarceration (without mass protest) of “dangerous populations,” almost any young black man, Latino gang members, and small-fry neighborhood drug dealers. The normalization of long-term solitary confinement in Security Housing Units (SHUs) in US prisons crosses over into the realm of torture and crimes against humanity.
Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer?
Authors: Grove Carolyn S. , Vassiliou George S.
Published: July 2014

Acute myeloid leukaemia (AML) is an uncontrolled clonal proliferation of abnormal myeloid progenitor cells in the bone marrow and blood. Advances in cancer genomics have revealed the spectrum of somatic mutations that give rise to human AML and drawn our attention to its molecular evolution and clonal architecture. It is now evident that most AML genomes harbour small numbers of mutations, which are acquired in a stepwise manner. This characteristic, combined with our ability to identify mutations in individual leukaemic cells and our detailed understanding of normal human and murine haematopoiesis, makes AML an excellent model for understanding the principles of cancer evolution. Furthermore, a better understanding of how AML evolves can help us devise strategies to improve the therapy and prognosis of AML patients. Here, we draw from recent advances in genomics, clinical studies and experimental models to describe the current knowledge of the clonal evolution of AML and its implications for the biology and treatment of leukaemias and other cancers.