bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlates of Delayed Diagnosis among Human Immunodeficiency Virus-Infected Pulmonary Tuberculosis Suspects in a Rural HIV Clinic, South Africa
Authors: Boniface Respicious , Moshabela Mosa , Zulliger Rose , MacPherson Peter , Nyasulu Peter
Published: June 2012

Background.Delay in pulmonary tuberculosis (PTB) diagnosis is one of the major factors that affect outcome and threatens continued spread of tuberculosis. This study aimed at determining factors associated with delayed PTB diagnosis among human immunodeficiency virus (HIV) infected individuals.Methods.A retrospective observational study was done using clinic records of HIV-infected PTB suspects attending an HIV/AIDS clinic at Tintswalo rural hospital in South Africa (SA) between January 2006 and December 2007. Using routine clinic registers, 480 records were identified.Results.PTB diagnosis delay was found among 77/176 (43.8%) of the patients diagnosed with PTB. The mean delay of PTB diagnosis was 170.6 days; diagnosis delay ranged 1–30 days in 27 (35.1%) patients, 31–180 days in 24 (33.8%) patients; 24 (31.2%) patients remained undiagnosed for ≥180 days. Independent factors associated with delayed diagnosis were: older age >40 years (Odds Ratio (OR) 3.43, 95% CI 1.45–8.08) and virological failure (OR 2.72, 95% CI 1.09–6.74).Conclusion.There is a considerable delayed PTB diagnosis among HIV-infected patients in rural SA. Older patients as well as patients with high viral load are at a higher risk of PTB diagnosis delay. Therefore efforts to reduce PTB diagnosis delay need to emphasised.
Chelators in the Treatment of Iron Accumulation in Parkinson's Disease
Authors: Mounsey Ross B. , Teismann Peter
Published: June 2012

Iron is an essential element in the metabolism of all cells. Elevated levels of the metal have been found in the brains of patients of numerous neurodegenerative disorders, including Parkinson's disease (PD). The pathogenesis of PD is largely unknown, although it is thought through studies with experimental models that oxidative stress and dysfunction of brain iron homeostasis, usually a tightly regulated process, play significant roles in the death of dopaminergic neurons. Accumulation of iron is present at affected neurons and associated microglia in the substantia nigra of PD patients. This additional free-iron has the capacity to generate reactive oxygen species, promote the aggregation ofα-synuclein protein, and exacerbate or even cause neurodegeneration. There are various treatments aimed at reversing this pathologic increase in iron content, comprising both synthetic and natural iron chelators. These include established drugs, which have been used to treat other disorders related to iron accumulation. This paper will discuss how iron dysregulation occurs and the link between increased iron and oxidative stress in PD, including the mechanism by which these processes lead to cell death, before assessing the current pharmacotherapies aimed at restoring normal iron redox and new chelation strategies undergoing research.
CDK Inhibitors Upregulate BH3-Only Proteins to Sensitize Human Myeloma Cells to BH3 Mimetic Therapies
Authors: Chen Shuang , Dai Yun , Pei Xin-Yan , Myers Jennifer , Wang Li , Kramer Lora B. , Garnett Mandy , Schwartz Daniella M. , Su Florence , Simmons Gary L. , Richey Justin D. , Larsen Dustin G. , Dent Paul , Orlowski Robert Z. , Grant Steven
Published: June 2012

BH3 mimetic drugs induce cell death by antagonizing the activity of antiapoptotic Bcl-2 family proteins. Cyclin-dependent kinase (CDK) inhibitors that function as transcriptional repressors downregulate the Bcl-2 family member Mcl-1 and increase the activity of selective BH3 mimetics that fail to target this protein. In this study, we determined whether CDK inhibitors potentiate the activity of pan-BH3 mimetics directly neutralizing Mcl-1. Specifically, we evaluated interactions between the prototypical pan-CDK inhibitor flavopiridol and the pan-BH3 mimetic obatoclax in multiple myeloma (MM) cells in which Mcl-1 is critical for survival. Coadministration of flavopiridol and obatoclax synergistically triggered apoptosis in both drug-naïve and drug-resistant MM cells. Mechanistic investigations revealed that flavopiridol inhibited Mcl-1 transcription but increased transcription of Bim and its binding to Bcl-2/Bcl-xL. Obatoclax prevented Mcl-1 recovery and caused release of Bim from Bcl-2/Bcl-xL and Mcl-1, accompanied by activation of Bax/Bak. Whether administered singly or in combination with obatoclax, flavopiridol also induced upregulation of multiple BH3-only proteins, including BimEL, BimL, Noxa, and Bik/NBK. Notably, short hairpin RNA knockdown of Bim or Noxa abrogated lethality triggered by the flavopiridol/obatoclax combination in vitro and in vivo. Together, our findings show that CDK inhibition potentiates pan-BH3 mimetic activity through a cooperative mechanism involving upregulation of BH3-only proteins with coordinate downregulation of their antiapoptotic counterparts. These findings have immediate implications for the clinical trial design of BH3 mimetic-based therapies that are presently being studied intensively for the treatment of diverse hematopoietic malignancies, including lethal multiple myeloma. Cancer Res; 72(16); 4225–37. ©2012 AACR.
Inhibition of Akt Potentiates 2-DG–Induced Apoptosis via Downregulation of UPR in Acute Lymphoblastic Leukemia
Authors: DeSalvo Joanna , Kuznetsov Jeffim N. , Du Jianfeng , Leclerc Gilles M. , Leclerc Guy J. , Lampidis Theodore J. , Barredo Julio C.
Published: June 2012

The ability to pair the regulation of metabolism and cellular energetics with oncogenes and tumor suppressor genes provides cancer cells with a growth and survival advantage over normal cells. We investigated the mechanism of cell death induced by 2-deoxy-d-glucose (2-DG), a sugar analog with dual activity of inhibiting glycolysis and N-linked glycosylation, in acute lymphoblastic leukemia (ALL). We found that, unlike most other cancer phenotypes in which 2-DG only inhibits cell proliferation under normoxic conditions, ALL lymphoblasts undergo apoptosis. Bp-ALL cell lines and primary cells exhibited sensitivity to 2-DG, whereas T-ALL cells were relatively resistant, revealing phenotypic differences within ALL subtypes. Cotreatment with d-mannose, a sugar essential for N-linked glycosylation, rescues 2-DG–treated ALL cells, indicating that inhibition of N-linked glycosylation and induction of ER stress and the unfolded protein response (UPR) is the predominant mechanism of 2-DG's cytotoxicity in ALL. 2-DG–treated ALL cells exhibit upregulation of P-AMPK, P-Akt, and induction of ER stress/UPR markers (IRE1α, GRP78, P-eIF2α, and CHOP), which correlate with PARP cleavage and apoptosis. In addition, we find that pharmacologic and genetic Akt inhibition upregulates P-AMPK, downregulates UPR, and sensitizes ALL cells to remarkably low doses of 2-DG (0.5 mmol/L), inducing 85% cell death and overcoming the relative resistance of T-ALL. In contrast, AMPK knockdown rescues ALL cells by upregulating the prosurvival UPR signaling. Therefore, 2-DG induces ALL cell death under normoxia by inducing ER stress, and AKT and AMPK, traditionally thought to operate predominantly on the glycolytic pathway, differentially regulate UPR activity to determine cell death or survival. Mol Cancer Res; 10(7); 969–78. ©2012 AACR.
Gene Silencing of the Mitochondrial Adaptor p66
Shc
Suppresses Vascular Hyperglycemic Memory in Diabetes
Authors: Paneni Francesco , Mocharla Pavani , Akhmedov Alexander , Costantino Sarah , Osto Elena , Volpe Massimo , Lüscher Thomas Felix , Cosentino Francesco
Published: June 2012

Rationale:

Hyperglycemic memory may explain why intensive glucose control has failed to improve cardiovascular outcomes in patients with diabetes. Indeed, hyperglycemia promotes vascular dysfunction even after glucose normalization. However, the molecular mechanisms of this phenomenon remain to be elucidated.

Objective:

The present study investigated the role of mitochondrial adaptor p66
Shc
in this setting.

Methods and Results:

In human aortic endothelial cells (HAECs) exposed to high glucose and aortas of diabetic mice, activation of p66
Shc
by protein kinase C βII (PKCβII) persisted after returning to normoglycemia. Persistent p66
Shc
upregulation and mitochondrial translocation were associated with continued reactive oxygen species (ROS) production, reduced nitric oxide bioavailability, and apoptosis. We show that p66
Shc
gene overexpression was epigenetically regulated by promoter CpG hypomethylation and general control nonderepressible 5–induced histone 3 acetylation. Furthermore, p66
Shc
-derived ROS production maintained PKCβII upregulation and PKCβII-dependent inhibitory phosphorylation of endothelial nitric oxide synthase at Thr-495, leading to a detrimental vicious cycle despite restoration of normoglycemia. Moreover, p66
Shc
activation accounted for the persistent elevation of the advanced glycated end product precursor methylglyoxal. In vitro and in vivo gene silencing of p66
Shc
, performed at the time of glucose normalization, blunted ROS production, restored endothelium-dependent vasorelaxation, and attenuated apoptosis by limiting cytochrome
c
release, caspase 3 activity, and cleavage of poly (ADP-ribose) polymerase.

Conclusions:

p66
Shc
is the key effector driving vascular hyperglycemic memory in diabetes. Our study provides molecular insights for the progression of diabetic vascular complications despite glycemic control and may help to define novel therapeutic targets.
Racial Differences in Risks for First Cardiovascular Events and Noncardiovascular Death
Authors: Feinstein Matthew , Ning Hongyan , Kang Joseph , Bertoni Alain , Carnethon Mercedes , Lloyd-Jones Donald M.
Published: June 2012

Background—

No studies have compared first cardiovascular disease (CVD) events and non-CVD death between races in a competing risks framework, which examines risks for numerous events simultaneously.

Methods and Results—

We used competing Cox models to estimate hazards for first CVD events and non-CVD death within and between races in 3 multicenter, National Heart, Lung, and Blood Institute–sponsored cohorts. Of 14 569 Atherosclerosis Risk in Communities (ARIC) study participants aged 45 to 64 years with mean follow-up of 10.5 years, 11.6% had CVD and 5.0% had non-CVD death as first events; among 4237 Cardiovascular Health Study (CHS) study participants aged 65 to 84 years and followed for 8.5 years, these figures were 43.2% and 15.7%, respectively. Middle-aged blacks were significantly more likely than whites to experience any CVD as a first event; this disparity disappeared by older adulthood and after adjustment for CVD risk factors. The pattern of results was similar for Multi-Ethnic Study of Atherosclerosis (MESA) participants. Traditional Cox and competing risks models yielded different results for coronary heart disease risk. Black men appeared somewhat more likely than white men to experience coronary heart disease with use of a standard Cox model (hazard ratio 1.06; 95% CI 0.90, 1.26), whereas they appeared less likely than white men to have a first coronary heart disease event with use of a competing risks model (hazard ratio, 0.77; 95% CI, 0.60, 1.00).

Conclusions—

CVD affects blacks at an earlier age than whites; this may be attributable in part to elevated CVD risk factor levels among blacks. Racial disparities in first CVD incidence disappear by older adulthood. Competing risks analyses may yield somewhat different results than traditional Cox models and provide a complementary approach to examining risks for first CVD events.
Incidence, Event Rates, and Early Outcome of Stroke in Dublin, Ireland
Authors: Kelly Peter J. , Crispino Gloria , Sheehan Orla , Kelly Lisa , Marnane Michael , Merwick Aine , Hannon Niamh , Ní Chróinín Danielle , Callaly Elizabeth , Harris Dawn , Horgan Gillian , Williams Emma B. , Duggan Joseph , Kyne Lorraine , McCormack Patricia , Dolan Eamon , Williams David , Moroney Joan , Kelleher Cecily , Daly Leslie
Published: June 2012

Background and Purpose—

The World Health Organization has emphasized the importance of international population-based data for unbiased surveillance of stroke incidence and outcome. To date, few such studies have been conducted using recommended gold-standard ascertainment methods. We conducted a large, population-based stroke study in Dublin, Ireland.

Methods—

Using gold-standard ascertainment methods, individuals with stroke and transient ischemic attack occurring over a 12-month period (December 1, 2005–November 30, 2006) in North Dublin were identified. Disability was assessed using the modified Rankin score and stroke severity (<72 hours) by the National Institutes of Health Stroke Scale. Stroke-related deaths were confirmed by review of medical files, death certificates, pathology, and coroner's records. Crude and standardized (to European and World Health Organization standard populations) rates of incidence, risk factors, severity, and early outcome (mortality, case-fatality, disability) were calculated, assuming a Poisson distribution for the number of events.

Results—

Seven hundred one patients with new stroke or transient ischemic attack were ascertained (485 first-ever stroke patients, 83 recurrent stroke patients, 133 first-ever transient ischemic attack patients). Crude frequency rates (all rates per 1000 person-years) were: 1.65 (95% CI, 1.5–1.79; first-ever stroke), 0.28 (95% CI, 0.22–0.35; recurrent stroke), and 0.45 (95% CI, 0.37–0.53; first-ever transient ischemic attack). Age-adjusted stroke rates were higher than those in 9 other recent population-based samples from high-income countries. High rates of subtype-specific risk factors were observed (atrial fibrillation, 31.3% and smoking, 29.1% in ischemic stroke; warfarin use, 21.2% in primary intracerebral hemorrhage; smoking, 53.9% in subarachnoid hemorrhage;
P
<0.01 for all compared with other subtypes). Compared with recent studies, 28-day case-fatality rates for primary intracerebral hemorrhage (41%; 95% CI, 29.2%–54.1%) and subarachnoid hemorrhage (46%; 95% CI, 28.8%–64.5%) were greater in Dublin.

Conclusions—

Using gold-standard methods for case ascertainment, we found high incidence rates of stroke in Dublin compared with those in similar high-income countries; this is likely explained in part by high rates of subtype-specific risk factors.
Cerebral Hemodynamic Changes in Stroke During Sleep-Disordered Breathing
Authors: Pizza Fabio , Biallas Martin , Kallweit Ulf , Wolf Martin , Bassetti Claudio L.
Published: June 2012

Background and Purpose—

Sleep-disordered breathing (SDB) negatively impacts stroke outcome. Near-infrared spectroscopy showed the acute cerebral hemodynamic effects of SDB.

Methods—

Eleven patients (7 men, age 61±13 years) with acute/subacute middle cerebral artery stroke (National Institutes of Health Stroke Scale score 10±7) and SDB (apnea–hypopnea index 32±28/hour) were assessed with nocturnal polysomnography and bilateral near-infrared spectroscopy recording. Cerebral oxygenation and hemoglobin concentration changes during obstructive and central apneas were analyzed.

Results—

During SDB, near-infrared spectroscopy showed asymmetrical patterns of cerebral oxygenation and hemoglobin concentrations with changes significantly larger on the unaffected compared with the affected hemisphere. Brain tissue hypoxia was more severe during obstructive compared with central apneas.

Conclusions—

Profound cerebral deoxygenation effects of SDB occurred in acute/subacute stroke. These changes may contribute to poor outcome, arising in the possibility of a potential benefit of SDB treatment in stroke management.
A bridging model prediction of the ultimate strength of composite laminates subjected to triaxial loads
Authors: Zhou Ye-Xin , Huang Zheng-Ming
Published: June 2012

A pseudo three-dimensional laminate theory is incorporated with the three-dimensional bridging model, based on micromechanics formulae, to predict failure under triaxial loads. A lamina failure is considered to occur as long as any of its constituents has failed. A laminate ultimate failure is assumed to take place when the fibres have failed or when the resin has failed in compression. In order to account for the effect of a three-dimensional compression on increasing the load-carrying ability of a resin material, a modified maximum compressive stress failure criterion is introduced. The methodology was used successfully to solve all the 12 challenging test cases of the Second World-Wide Failure Exercise.
Leading by Example to Protect the Environment
Authors: Van der Heijden Eline , Moxnes Erling
Published: June 2012

Environmentalists often urge their home countries to take a leading role in reducing global environmental problems like climate change. A pertinent question is, Will examples set by leading nations influence others to follow suit, and if so, do the costs of leading matter? For instance, will costly domestic reductions have a stronger effect on followers than purchases of cheap emission permits abroad? To investigate these questions, we have conducted two treatments in a public bad experiment in which leaders have different costs of leading. Our findings suggest that higher costs of leading lead to stronger effects of a given leader example. Randomly chosen leaders lead by example and set better examples if it is less costly to do so. Finally, there seems to be a limit to the leader effect and it may decrease over time.
Propranolol Reduces Infantile Hemangioma Volume and Vessel Density
Authors: Bingham Matthew M. , Saltzman Babette , Vo Nghia‐Jack , Perkins Jonathan A.
Published: June 2012

Objective

To evaluate changes in infantile hemangioma tissue before and after propranolol therapy, using gray‐scale and color Doppler ultrasound imaging.

Study Design

Case series with chart review.

Setting

Tertiary pediatric hospital.

Subjects and Methods

Medical records and image studies of head and neck infantile hemangioma patients treated with propranolol, identified in a quality improvement database, were reviewed. Patients with imaging before and at least 4 weeks following the initiation of treatment were included. Data collected included sex, age, location, and concurrent treatment. Student t tests were used to evaluate change in cutaneous lesion area, volume, and vessel density. Logistic regression was used to compare lesion area, volume, and vessel density.

Results

Of the 177 patients identified, 19 met inclusion criteria. Fourteen of 19 were female, and 5 of 19 were older than 1 year. Mean lesion area change with treatment was 13.0 cm2 (range, −2.8 to 28.9 cm2, P =. 05). Measured volume change was a mean of 10.3 cm3 (range, 1.5‐19.2 cm3, P =. 01). Mean vessel density change was 4.4 vessels per cm2 (range, 2.5‐6.3 vessels per cm2, P <. 01). Treatment decreased clinically determined hemangioma area proportionately less than gray‐scale and color Doppler ultrasound measured lesion volume. Gray‐scale and color Doppler ultrasound measured treatment response did not differ with sex, lesion location, or age at propranolol initiation.

Conclusion

Gray‐scale and color Doppler ultrasound imaging of propranolol‐treated infantile hemangiomas detected a significant reduction in lesion volume and vessel density. Patient age at propranolol treatment and concomitant corticosteroid use did not affect lesion volume change.
Wales in the age of austerity
Authors: Drakeford Mark
Published: June 2012

Austerity in Wales has to be understood in the context of the more general budgetary limitations created by the out-dated Barnett formula and the current debates in Wales (and Scotland) about the ways in which devolved functions should be funded in the future. This paper identifies the key measures which successive administrations have taken in support of an essentially Keynesian, counter-cyclical approach to countering recession in Wales. It traces the outcomes of the May 2011 Assembly election and the emerging policy and legislative agenda of the minority Labour administration which that election produced. The paper ends by placing these developments within the wider austerity agenda pursued by the Westminster coalition and its deleterious impact on Wales.
Nonlesions, Unusual Cell Types, and Postmortem Artifacts in the Central Nervous System of Domestic Animals
Authors: Wohlsein P. , Deschl U. , Baumgärtner W.
Published: June 2012

In the central nervous system (CNS) of domestic animals, numerous specialized normal structures, unusual cell types, findings of uncertain or no significance, artifacts, and various postmortem alterations can be observed. They may cause confusion for inexperienced pathologists and those not specialized in neuropathology, leading to misinterpretations and wrong diagnoses. Alternatively, changes may mask underlying neuropathological processes. “Specialized structures” comprising the hippocampus and the circumventricular organs, including the vascular organ of the lamina terminalis, subfornical organ, subcommissural organ, pineal gland, median eminence/neurohypophyseal complex, choroid plexus, and area postrema, are displayed. Unusual cell types, including cerebellar external germinal cells, CNS progenitor cells, and Kolmer cells, are presented. In addition, some newly recognized cell types as of yet incompletely understood significance and functionality, such as synantocytes and aldynoglia, are introduced and described. Unusual reactive astrocytes in cats, central chromatolysis, neuronal vacuolation, spheroids, spongiosis, satellitosis, melanosis, neuromelanin, lipofuscin, polyglucosan bodies, and psammoma bodies may represent incidental findings of uncertain or no significance and should not be confused with significant microscopic changes. Auto- and heterolysis as well as handling and histotechnological processing may cause postmortem morphological changes of the CNS, including vacuolization, cerebellar conglutination, dark neurons, Buscaino bodies, freezing, and shrinkage artifacts, all of which have to be differentiated from genuine lesions. Postmortem invasion of micro-organisms should not be confused with intravital infections. Awareness of these different changes and their recognition are a prerequisite for identifying genuine lesions and may help to formulate a professional morphological and etiological diagnosis.
Double-Bundle Versus Single-Bundle Anterior Cruciate Ligament Reconstruction
Authors: Suomalainen Piia , Järvelä Timo , Paakkala Antti , Kannus Pekka , Järvinen Markku
Published: June 2012

Background:

Surgical technique is essential in anterior cruciate ligament (ACL) reconstruction.

Purpose:

This randomized 5-year study tested the hypothesis that double-bundle ACL reconstruction with hamstring autografts and aperture screw fixation has fewer graft ruptures and rates of osteoarthritis (OA) and better stability than single-bundle reconstruction.

Study Design:

Randomized controlled trial; Level of evidence, 1.

Methods:

Ninety patients were randomized: double-bundle ACL reconstruction with bioabsorbable screw fixation (DB group; n = 30), single-bundle ACL reconstruction with bioabsorbable screw fixation (SBB group; n = 30), and single-bundle ACL reconstruction with metallic screw fixation (SBM group; n = 30). The following evaluation methods were used: clinical examination, KT-1000 arthrometer measurement, and International Knee Documentation Committee (IKDC) and Lysholm knee scores. Additionally, radiographic evaluation was made by a musculoskeletal radiologist who was unaware of the patients’ clinical and surgical data. A single orthopaedic surgeon performed all the operations, and clinical follow-up assessments were made in a blinded manner by an independent examiner.

Results:

Preoperatively, there were no differences between the groups. Eleven patients (7 in the SBB group, 3 in the SBM group, and 1 in the DB group) had a graft failure during the follow-up and went on to ACL revision surgery ( P < .043). Of the remaining 79 patients, a 5-year follow-up was performed for 65 patients (20 in the DB group, 21 in the SBB group, and 24 in the SBM group) who had their grafts intact. At 5 years, there was no statistically significant difference in the pivot-shift or KT-1000 arthrometer tests. In the DB group, 20% of the patients had OA in the medial femorotibial compartment and 10% in the lateral compartment, while the corresponding figures were 33% and 18% in the single-bundle groups, again an insignificant finding. Further, no significant group differences were found in the knee scores.

Conclusion:

The double-bundle surgery resulted in significantly fewer graft failures and subsequent revision ACL surgery than the single-bundle surgeries during the 5-year follow-up. Knee stability and OA rates were similar at 5 years. In view of the size of the groups, some caution should be exercised when interpreting the lack of difference in the secondary outcomes.
Biomechanical Properties of Porcine Flexor Tendon Fixation With Varying Throws and Stitch Methods
Authors: Sakaguchi Katsunobu , Tachibana Yomei , Oda Hiromi
Published: June 2012

Background:

The well-known suture technique configurations used for hamstring tendon autograft preparation in anterior cruciate ligament (ACL) reconstruction are the Krackow locking stitch and nonlocking stitch, such as a baseball stitch and a whipstitch. However, there are few data in the literature regarding biomechanical comparisons of suture techniques.

Purpose:

The purpose of this study was to determine the properties of several current techniques of tendon graft suture employed in ACL reconstruction.

Study Design:

Controlled laboratory study.

Methods:

Forty-two fresh-frozen porcine flexor digitorum tendons were used. Three stitch configurations (Krackow stitch [group K], baseball stitch [group B], and whipstitch [group W]) were assessed with varying suture throws (6 throws, group×6; 10 throws, group×10) using No. 5 Ethibond sutures. Each group was tested at 1500 loading cycles between 50 and 200 N. After loading cycles, the surviving tendons underwent a load-to-failure test.

Results:

During the loading cycles, 3 of 7 specimens in group B×6 and all specimens in group W×6 failed by suture pullout. Four of 7 specimens in group B×10 and all specimens in group W×10 showed partial tearing of the tendon. Elongation of group B×10 and group W×10 showed significantly greater elongation than other groups ( P < .05). Maximum loads at failure showed significant differences between group K and the other groups (K×6, 436 ± 52 N; K×10, 419 ± 34 N; P < .05). Most specimens failed by rupture of the suture thread in group K. Pullout of the suture from the tendon was observed most in groups B and W.

Conclusion:

The Krackow stitch was superior to other stitch methods. There was, however, no significant effect of the number of throws on the holding strength.

Clinical Relevance:

The Krackow stitch could prevent suture slippage by a locking mechanism. The whipstitch is not suitable for clinical application even with an increased number of throws.
The biocompatibility of a polyelectrolyte vitreous body substitute on a high resistance in vitro model of the blood-retinal barrier
Authors: Strotmann Falko , Wolf Isabel , Galla Hans-Joachim
Published: June 2012

The vitreous body can be regarded as a fascinating simple but important tissue, since it represents the main compartment of the eye and plays a crucial role for proper vision. Several diseases require its removal with following substitution using a liquid artificial vitreous body replacement. We explore the biocompatibility of a poly(AMPS-Na+)-graft-poly(NIPAAm) polyelectrolyte following the innovative concept of thermo-responsive behaviour, exhibiting enhanced shear viscosity at physiological temperatures. As a powerful model for the blood-retinal barrier, we use the well-established in vitro cell culture model based on highly differentiated porcine brain capillary endothelial cells. Via the quantification of the transendothelial electrical resistance and immunocytochemical staining of tight junction proteins, we are able to show that a barrier integrity affecting impact of the polyelectrolyte was only transient and nearly reversible. Furthermore, the polyelectrolyte hydrogel is characterized by the absence of any acute cell morphology, cell vitality or proliferation affecting impacts. It does not trigger acute apoptotic processes, as can be substantiated via caspase-3 activity and DNA fragmentation assays. In view of the results of this study, it is shown that the polyelectrolyte does not affect the vitality parameters of our porcine brain capillary endothelial cells. It can be suggested that the tested thermo-responsive polyelectrolyte does not affect the sensitive retinal barrier integrity. Thus from the cellular tolerance it might serve as a potential liquid artificial vitreous body replacement to overcome the most prominent difficulties of common vitreal endotamponades.
In-cylinder boosting of turbocharged spark-ignited engines. Part 2: Control and experimental verification
Authors: Voser Christoph , Ott Tobias , Dönitz Christian , Onder Christopher , Guzzella Lino
Published: June 2012

Downsizing and turbocharging is a common approach to improve the fuel economy of spark-ignited combustion engines. However, the inherent turbo lag results in a loss of driveability. In-cylinder boosting is an effective way to eliminate this problem. In the first part of this two-part study, a deactivatable camshaft-driven valve controlling the air mass flow from a pressurised air-tank directly into the cylinder was proposed as the main actuator of such a system, where also a model-based design procedure was demonstrated. In this paper, the torque control during the turbo lag compensation is discussed. The control is complicated by the limited variability of the mechanical valve-train. This limited variability gives rise to a trade-off between fuel and pressurised air consumption. However, the proposed control strategy minimising the consumption of pressurised air (thereby minimising the space required for the pressurised air tank), causes only a small penalty in fuel consumption. This air-mass-based control strategy actuating the throttle, ignition timing and boost mode timing is analysed in simulation and then verified experimentally in various operating conditions.
Clinical research ethics in Irish healthcare
Authors: Condell Sarah L , Begley Cecily
Published: June 2012

Gaining ethical clearance to conduct a study is an important aspect of all research involving humans but can be time-consuming and daunting for novice researchers. This article stems from a larger ethnographic study that examined research capacity building in Irish nursing and midwifery. Data were collected over a 28-month time frame from a purposive sample of 16 nurse or midwife research fellows who were funded to undertake full-time PhDs. Gaining ethical clearance for their studies was reported as an early ‘rite of passage’ in the category of ‘labouring the doctorate’. This article penetrates the complexities in Irish clinical research ethics by describing the practices these nurse and midwife researchers encountered and the experiences they had. The key issue of representation that occurred in the context of ‘medicalized’ research ethics is further explored including its meaning for nursing or midwifery research.
Low-salt restructured fish products from Atlantic mackerel (Scomber scombrus) with texture resembling turkey breast
Authors: Martelo-Vidal MJ , Mesas JM , Vázquez M
Published: June 2012

Atlantic mackerel ( Scomber scombrus) is a pelagic and migratory species that is usually caught with other fish as bycatch. The aim of this work was to obtain low-salt restructured fish products from Atlantic mackerel resembling turkey breast using transglutaminase (0.2 U/g) as binder. NaCl concentration (0–20 g/kg), temperature (25–40 °C) and time of incubation (30–90 min) were assayed. The texture parameters (Warner–Bratzler force and Warner–Bratzler work) and expressible water were compared to those of turkey breast. Mathematical models were obtained to determine the effect of these variables on the texture of Atlantic mackerel restructured products. Optimal conditions to obtain a similar texture than turkey breast were found. The overall optimization point out that the treatment at 31.8 °C for 63.35 min using a NaCl concentration of 8.45 g/kg allowed to obtain restructured products from Atlantic mackerel with texture and expressible water similar to those of turkey breast. Color parameters ( L*, a* and b*) of the product were also similar to those of turkey breast. The results showed the feasibility of producing low-salt restructured products from Atlantic mackerel resembling turkey breast using transglutaminase.
Public Spending Composition in Uganda and its Implications for Growth and Poverty Reduction
Authors: Sennoga Edward Batte , Matovu John Mary
Published: June 2012

This article examines the interrelationships between public spending composition and Uganda’s development goals including economic growth and poverty reduction. The authors utilize a dynamic computable general equilibrium model to study these interrelationships. These results demonstrate that public spending composition does indeed influence economic growth and poverty reduction. In particular, the authors show that improved public sector efficiency coupled with reallocation of public expenditure away from the unproductive sectors such as public administration and security to the productive sectors including agriculture, energy, water, and health leads to higher gross domestic product growth rates and accelerates poverty reduction. Moreover, the rate of poverty reduction is faster in rural households relative to the urban households. A major contribution of this article is that investments in agriculture, particularly with a view to promoting value addition and investing in complementary infrastructure (e.g., roads and affordable energy), contribute to higher economic growth rates and also accelerate the rate of poverty reduction.
Enriching CA through MCA? Stokoe’s MCA keys
Authors: Gardner Rod
Published: June 2012

In this commentary on Stokoe’s article, ‘Moving forward with membership categorization analysis’, I take up the challenge to apply her keys for MCA to an extract of conversation recorded in a restaurant. The strengths of conversation analysis have not included – and indeed have not attempted to achieve – successful engagement with beyond-the-immediate-talk aspects of culture and the commonsense workings of society. The aim of the article is to explore what MCA might add to an analysis of a stretch of talk using conversation analytic tools. It was found that a systematic application of the keys did indeed provide a richer account of what was going on. Whereas categories alone did not appear to provide more insights than commonsense can tell us, when the broader array of MCA tools and keys were applied, an enhanced analysis of the passage of talk emerged. An exploration of whether this can be extended as a method for a rigorous investigation of culture and society while still being grounded in participants’ mutual, moment-by-moment orientations to categories seems at the very least worth the serious attention of scholars interested in interaction.
Everyday resilience: Narratives of single refugee women with children
Authors: Lenette Caroline , Brough Mark , Cox Leonie
Published: June 2012

This article offers a critical exploration of the concept of resilience, which is largely conceptualized in the literature as an extraordinary atypical personal ability to revert or ‘bounce back’ to a point of equilibrium despite significant adversity. While resilience has been explored in a range of contexts, there is little recognition of resilience as a social process arising from mundane practices of everyday life and situated in person-environment interactions. Based on an ethnographic study among single refugee women with children in Brisbane, Australia, the women’s stories on navigating everyday tensions and opportunities revealed how resilience was a process operating inter-subjectively in the social spaces connecting them to their environment. Far beyond the simplistic binaries of resilience versus non-resilient, we concern ourselves here with the everyday processual, person-environment nature of the concept. We argue that more attention should be paid to day-to-day pathways through which resilience outcomes are achieved, and that this has important implications for refugee mental health practice frameworks.
Masculinity Beliefs Predict Psychosocial Functioning in African American Prostate Cancer Survivors
Authors: Campbell Lisa C. , Keefe Francis J. , McKee Daphne C. , Waters Sandra J. , Moul Judd W.
Published: June 2012

Research examining psychosocial functioning in African American prostate cancer survivors has been limited, in spite of documented higher mortality from prostate cancer and worse long-term physical and emotional outcomes from prostate cancer treatment reported by this group of survivors. In addition, the role of masculinity in psychosocial adjustment among prostate cancer survivors is not well understood. In this study, 59 African American prostate cancer survivors completed a questionnaire assessing masculinity beliefs related to self-reliance, emotional control, and dominance, as well as measures of psychosocial functioning (i.e., symptom distress, negative mood, and functional and social well-being). Results of regression analyses indicated that masculinity beliefs predicted negative mood, functional well-being, and social well-being, controlling for age, income, and medical comorbidities. The findings reported here, although preliminary, suggest that masculinity beliefs could be important therapeutic targets for improving the efficacy of cognitive-behavioral interventions for men adjusting to prostate cancer survivorship.
Mikhail Bakhtin and the Field of Law and Literature
Authors: Manderson Desmond
Published: June 2012

This essay takes as its focus the work of Mikhail Bakhtin, a leading literary theorist who has, to date, received relatively little attention in the field of law and literature. Central themes in the work of Bakhtin include the dialogic quality of the novel and its ethical implications, its commitment to singularity and context, its comprehensive critique of authority and, tying all of these features together, the importance of form and style to our understanding of the experience of literature. These themes all pay attention less to the subject-matter or content of particular works of literature than to its historical trajectory, its distinctive characteristics, and its approach to language. This is perhaps one important way in which Bakhtin’s approach is distinct from the focus on ‘‘narrative’’ which is so much the staple of law and literature writing. The novel’s ‘‘heteroglossia,’’ as Bakhtin puts it – its irony, ambiguity, and ‘‘doubleness’’ – is neither a serendipitous features of certain texts nor a secondary element of normatively driven ‘‘story-telling,’’ but structural and stylistic characteristics of the novel as such. Bakhtin thus problematizes the treatment of narrative and the authenticity of voice assumed in much of the standard literature. While Bakhtin brings to these arguments an unprecedented sweep and command of detail, and a highly distinctive vocabulary for analysis, his arguments parallel the work of the other twentieth-century writers on literature. In particular, writing at the same critical historical moment, Bakhtin’s claims are echoed in D.H. Lawrence’s own essays on the novel, and illustrated – indeed, performed – in his fiction.
The Changing Relationship Between Labor and the State in Contemporary Capitalism
Authors: Howell Chris
Published: June 2012

Over the course of the past quarter century, paralleling the decline of organized labor, there has been a marked increase in the role of the state in the industrial relations of advanced capitalist societies. This has come both in the form of state activism in the reconstruction of institutions, and through the replacement of collective self-regulation by employer and labor organizations with legal regulation. Unsurprisingly, these developments have failed to encourage a renewal of trade union collective power, leaving workers increasingly insecure, dependent upon markets, and vulnerable to the vagaries of state power.
‘It’s possible to play the game marvellously and at the same time look pretty and be perfectly fit’: Sport, Women and Fashion in Inter-war Britain
Authors: Skillen Fiona
Published: June 2012

This article will examine the development of women’s increasing participation in sport and its impact on the subsequent emergence of sportswear for women in inter-war Britain. It will explore the public discourses which surrounded these women and their clothes in order to point up the complex nature of the problems women faced when making decisions about what to wear for sports activities.
Study of the catalytic activity of Al-Fe pillared clays in the Baeyer–Villiger oxidation
Authors: Belaroui L. S. , Bengueddach A.
Published: June 2012

Three types of AlFePILCs pillared clays have been prepared from Algerian clay precursors. They have been characterized and tested in the Baeyer–Villiger oxidation of cyclohexanone to caprolactone using benzaldehyde and oxygen as oxidant at room temperature. The structural and textural properties of the catalyst have been determined by X-ray diffraction, nitrogen adsorption-desorption isotherms and Mössbauer spectroscopy.

The different activities of the clays have been related to their Fe contents and accessible surface areas. The induction period observed before the reaction started has been attributed to the dissolution of a portion of the Fe3+ cations, mediated by either the perbenzoic acid intermediate or the benzoic acid co-product. The reaction was indeed catalysed by a few ppm of dissolved iron cations and the catalysis of the Baeyer–Villiger oxidation reaction should mechanistically be considered as homogeneous.
The arsenic-based cure of acute promyelocytic leukemia promotes cytoplasmic sequestration of PML and PML/RARA through inhibition of PML body recycling
Authors: Lång Emma , Grudic Amra , Pankiv Serhiy , Bruserud Øystein , Simonsen Anne , Bjerkvig Rolf , Bjørås Magnar , Bøe Stig Ove
Published: June 2012

Arsenic in the form of arsenic trioxide (ATO) is used as a therapeutic drug for treatment of acute promyelocytic leukemia (APL). The mechanism by which this agent cures this disease was previously shown to involve direct interactions between ATO and the promyelocytic leukemia protein (PML), as well as accelerated degradation of the APL-associated fusion oncoprotein PML/retinoic acid receptor α (RARA). Here we investigated the fate of PML-generated nuclear structures called PML bodies in ATO-treated cells. We found that ATO inhibits formation of progeny PML bodies while it stabilizes cytoplasmic precursor compartments, referred to as cytoplasmic assemblies of PML and nucleoporins (CyPNs), after cell division. This block in PML body recycling is readily detected at pharmacologic relevant ATO concentrations (0.02-0.5μM) that do not cause detectable cell-cycle defects, and it does not require modification of PML by SUMOylation. In addition, PML and PML/RARA carrying mutations previously identified in ATO-resistant APL patients are impeded in their ability to become sequestered within CyPNs. Thus, ATO may inhibit nuclear activities of PML and PML/RARA in postmitotic cells through CyPN-dependent cytoplasmic sequestration.
Overexpression of TCL1 activates the endoplasmic reticulum stress response: a novel mechanism of leukemic progression in mice
Authors: Kriss Crystina L. , Pinilla-Ibarz Javier A. , Mailloux Adam W. , Powers John J. , Tang Chih-Hang Anthony , Kang Chang Won , Zanesi Nicola , Epling-Burnette Pearlie K. , Sotomayor Eduardo M. , Croce Carlo M. , Del Valle Juan R. , Hu Chih-Chi Andrew
Published: June 2012

Chronic lymphocytic leukemia (CLL) represents 30% of adult leukemia. TCL1 is expressed in ∼ 90% of human CLL. Transgenic expression of TCL1 in murine B cells (Eμ-TCL1) results in mouse CLL. Here we show for the first time that the previously unexplored endoplasmic reticulum (ER) stress response is aberrantly activated in Eμ-TCL1 mouse and human CLL. This includes activation of the IRE-1/XBP-1 pathway and the transcriptionally up-regulated expression of Derlin-1, Derlin-2, BiP, GRP94, and PDI. TCL1 associates with the XBP-1 transcription factor, and causes the dysregulated expression of the transcription factors, Pax5, IRF4, and Blimp-1, and of the activation-induced cytidine deaminase. In addition, TCL1-overexpressing CLL cells manufacture a distinctly different BCR, as we detected increased expression of membrane-bound IgM and altered N-linked glycosylation of Igα and Igβ, which account for the hyperactive BCR in malignant CLL. To demonstrate that the ER stress-response pathway is a novel molecular target for the treatment of CLL, we blocked the IRE-1/XBP-1 pathway using a novel inhibitor, and observed apoptosis and significantly stalled growth of CLL cells in vitro and in mice. These studies reveal an important role of TCL1 in activating the ER stress response in support for malignant progression of CLL.
How I manage pulmonary nodular lesions and nodular infiltrates in patients with hematologic malignancies or undergoing hematopoietic cell transplantation
Authors: Wingard John R. , Hiemenz John W. , Jantz Michael A.
Published: June 2012

Pulmonary nodules and nodular infiltrates occur frequently during treatment of hematologic malignancies and after hematopoietic cell transplantation. In patients not receiving active immunosuppressive therapy, the most likely culprits are primary lung cancer, chronic infectious or inactive granulomata, or even the underlying hematologic disease itself (especially in patients with lymphoma). In patients receiving active therapy or who are otherwise highly immunosuppressed, there is a wider spectrum of etiologies with infection being most likely, especially by bacteria and fungi. Characterization of the pulmonary lesion by high-resolution CT imaging is a crucial first diagnostic step. Other noninvasive tests can often be useful, but invasive testing by bronchoscopic evaluation or acquisition of tissue by one of several biopsy techniques should be performed for those at risk for malignancy or invasive infection unless contraindicated. The choice of the optimal biopsy technique should be individualized, guided by location of the lesion, suspected etiology, skill and experience of the diagnostic team, procedural risk of complications, and patient status. Although presumptive therapy targeting the most likely etiology is justified in patients suspected of serious infection while evaluation proceeds, a structured evaluation to determine the specific etiology is recommended. Interdisciplinary teamwork is highly desirable to optimize diagnosis and therapy.