bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative pharmacokinetics and pharmacodynamics of urocortins 1, 2 and 3 in healthy sheep
Authors: Patel K , Rademaker MT , Kirkpatrick CMJ , Charles CJ , Fisher S , Yandle TG , Richards AM
Published: February 2012

BACKGROUND AND PURPOSE The urocortin (Ucn) peptides are emerging as potential therapeutic targets for heart disease. However, pharmacokinetic (PK) and pharmacodynamic (PD) data are lacking. Therefore, we investigated the PK/PD for all three Ucns.

EXPERIMENTAL APPROACH Seven sheep received 1 µg·kg−1 boluses of Ucn1, Ucn2 and Ucn3. Population PK/PD models were developed to describe the time course of the haemodynamic effects.

RESULTS The population estimate for Ucn1 clearance (0.486 L·h−1) was lower than that for Ucn2 (21.7 L·h−1) and Ucn3 (220 L·h−1), while steady‐state volumes of distribution were similar for Ucn1 and Ucn2 (∼8 L) but substantially larger for Ucn3 (23.5 L). Ucn1 disposition was adequately described by a two‐compartment model, with a one‐compartment model required for Ucn2 and Ucn3. The half‐life for Ucn1 was 2.9 h (α phase) and 8.3 h (β phase), and 15.7 and 4.4 min for Ucn2 and Ucn3 respectively. All Ucns produced significant increases in heart rate, cardiac output and left ventricular systolic and mean arterial pressures, and decreases in left atrial pressure and peripheral resistance. Delayed‐effect pharmacodynamic models best described the time course of haemodynamic responses, with effects more rapid and less prolonged for Ucn2 and Ucn3 than Ucn1. Similar and physiologically plausible estimated baseline (E0) effects were exhibited by all Ucns, whereas EC50 values were generally greater for Ucn1.

CONCLUSIONS AND IMPLICATIONS Relative to Ucn1, both the PK and haemodynamic responses to Ucn2 and Ucn3 occurred more rapidly. Our data provide important comparative information, useful to the rational design of future clinical studies.
Contribution of PARP to endothelial dysfunction and hypertension in a rat model of pre‐eclampsia
Authors: Walsh SK , English FA , Crocker IP , Johns EJ , Kenny LC
Published: February 2012

BACKGROUND AND PURPOSE Under conditions of increased oxidative stress, such as pre‐eclampsia and diabetes, overstimulation of PARP leads to endothelial dysfunction. Inhibition of PARP has been demonstrated to reverse the vascular dysfunction associated with diabetes in vivo. The present study was carried out to investigate the role of PARP in mediating the endothelial dysfunction associated with pre‐eclampsia.

EXPERIMENTAL APPROACH Uteroplacental perfusion was surgically reduced in pregnant rats to produce the reduced uterine perfusion pressure (RUPP) rat model of pre‐eclampsia and the PARP inhibitor, PJ34, was administered either before or after surgery. Mean arterial BP and vascular function were measured in normal pregnant (NP) and both control and PJ34‐treated RUPP rats. Mesenteric vessels from NP rats were incubated with either 3% RUPP or NP plasma alone or in combination with PJ34. Finally, immunohistochemical staining was carried out to measure nitrotyrosine (byproduct of peroxynitrite) immunoreactivity.

KEY RESULTS RUPP rats were characterized by hypertension, fetal growth restriction and endothelial dysfunction when compared with NP rats. PJ34 administered in vivo before, but not after, surgery prevented the development of both endothelial dysfunction and hypertension. RUPP plasma‐induced impaired vasorelaxation was prevented following co‐incubation with PJ34 in vitro. Furthermore, the protective effect of PARP inhibition in vivo was accompanied by a reduction in nitrotyrosine immunoreactivity.

CONCLUSIONS AND IMPLICATIONS PJ34 prevented the development of both endothelial dysfunction and hypertension and reduced vascular nitrotyrosine immunoreactivity, thus suggesting a role for oxidative–nitrosative stress/PARP activation in the aberration in both vascular and haemodynamic function in this rat model of pre‐eclampsia.
Rivastigmine patch for treatment of Alzheimer's disease in clinical practice in Thailand
Authors: KULKANTRAKORN Kongkiat , TANYAKITPISAL Panas , TOWANABUT Somchai , DEJTHEVAPORN Charungthai , RANGSEEKAJEE Poonsri , PONGPAKDEE Sunsanee , LAPTIKULTHAM Somsak , RODPRASERT Kritsada , SETTHAWATCHARAWANICH Suwanna , THINKHAMROP Bandit
Published: February 2012

Background:  Rivastigmine is a cholinesterase inhibitor for treatment of mild to moderate Alzheimer's disease (AD) and dementia associated with Parkinson's disease. The new patch formulation was recently made available. We assessed the safety, tolerability, and cognitive outcome of rivastigmine patch in treatment of mild to moderate AD in clinical practice in Thailand.

Methods:  A multicentre, hospital‐based, prospective observational study was conducted in nine hospitals across Thailand. Patients with probable mild to moderate AD who received the rivastigmine patch were enrolled. Data were collected data at baseline, weeks 4–8 and after week16.

Results:  A total of 116 AD patients were screened, and three were excluded. Of 113 patients, 62.8% were women with a mean age of 73.3 ± 9.2 years; 79.7% were newly diagnosed. One‐third of all patients had been using antipsychotic or antidepressant medication. Common comorbidities were hypertension and dyslipidemia. The Thai Mental State Examination score significantly increased from 18.6 to 20.3 (weeks 4–8) and 20.4 (week 16+) (P < 0.001). Scores based on physicians’ (Clinical Global Impression) and caregivers’ (Patients’ Caregiver Global Impression of Change) impressions of improvement suggested minimal improvement. Because of adverse events, seven patients's dosages were reduced 10 cm2 to 5 cm2 or from 5 cm2 to nothing. Itching was the most common adverse symptom.

Conclusions:  During the first 16 weeks after initiation of rivastigmine patch therapy, patients with probable mild to moderate AD had statistically significant improvement in cognitive function, but clinically marginal benefit. Rivastigmine was safe and well tolerated.
Clinically significant red blood cell antibodies in chronically transfused patients: a survey of Chinese thalassemia major patients and literature review
Authors: Cheng C.K. , Lee C.K. , Lin C.K.
Published: February 2012

BACKGROUND: Red blood cell (RBC) alloimmunization is reported to occur at an incidence of 5.2% to 23.5% among patients with thalassemia requiring chronic transfusion. With very limited data on alloimmunization among the Chinese population, a territory‐wide study has been performed to look at its prevalence among Chinese thalassemia major patients.

STUDY DESIGN AND METHODS: A retrospective study was conducted by reviewing RBC request records for patients with thalassemia major in Hong Kong from 2006 to 2009. Demographic information and serologic data were retrieved for analysis.

RESULTS: A total of 382 patients were identified and consisted of 190 males and 192 females with a median age of 23 ± 10.4 (range, 0.25 to 52) years. Eighty‐eight patients (23.0%) were reported to have RBC antibodies. Of them, 114 alloantibodies, 18 autoantibodies, and 19 unidentified antibodies were identified. Anti‐E (42, 39.3%), anti‐Mia/Mur (33, 30.85%), anti‐c (14, 13.1%), and anti‐Jka (seven, 6.55%) were the commonest antibodies reported. However, one case of anti‐K (0.9%) and two cases of anti‐Fyb (1.9%) were reported. Seven of the 18 patients with autoantibodies contained a total of 13 alloantibodies. They were anti‐E (five, 38.4%), anti‐Mia/Mur (four, 30.8%), anti‐Jka (two, 15.4%), anti‐c (one, 7.7%), and anti‐Fyb (one, 7.7%).

CONCLUSION: It is the first comprehensive study on Chinese thalassemia major patients. Clinically significant alloantibodies are different from those observed in the Western population, although antibodies developed against Rh antigens are still common. Chinese patients are less likely to have antibodies against Kell and Duffy blood group antigens, but are more prone to develop antibodies against the Miltenberger antigens.
An Academic‐Health Service Partnership in Nursing: Lessons From the Field
Authors: Granger Bradi B. , Prvu‐Bettger Janet , Aucoin Julia , Fuchs Mary Ann , Mitchell Pamela H. , Holditch‐Davis Diane , Roth Deborah , Califf Robert M. , Gilliss Catherine L.
Published: February 2012

Purpose: To describe the development of an academic‐health services partnership undertaken to improve use of evidence in clinical practice.

Approach: Academic health science schools and health service settings share common elements of their missions: to educate, participate in research, and excel in healthcare delivery, but differences in the business models, incentives, and approaches to problem solving can lead to differences in priorities. Thus, academic and health service settings do not naturally align their leadership structures or work processes. We established a common commitment to accelerate the appropriate use of evidence in clinical practice and created an organizational structure to optimize opportunities for partnering that would leverage shared resources to achieve our goal.

Findings: A jointly governed and funded institute integrated existing activities from the academic and service sectors. Additional resources included clinical staff and student training and mentoring, a pilot research grant‐funding program, and support to access existing data. Emergent developments include an appreciation for a wider range of investigative methodologies and cross‐disciplinary teams with skills to integrate research in daily practice and improve patient outcomes.

Conclusions: By developing an integrated leadership structure and commitment to shared goals, we developed a framework for integrating academic and health service resources, leveraging additional resources, and forming a mutually beneficial partnership to improve clinical outcomes for patients.

Clinical Relevance: Structurally integrated academic‐health service partnerships result in improved evidence‐based patient care delivery and in a stronger foundation for generating new clinical knowledge, thus improving patient outcomes.

Journal of Nursing Scholarship, 2011; XX:X, XXX–XXX. ©2011 Sigma Theta Tau International.
The human epidermal differentiation complex: cornified envelope precursors, S100 proteins and the ‘fused genes’ family
Authors: Kypriotou Magdalini , Huber Marcel , Hohl Daniel
Published: February 2012

Abstract:  The skin is essential for survival and protects our body against biological attacks, physical stress, chemical injury, water loss, ultraviolet radiation and immunological impairment. The epidermal barrier constitutes the primordial frontline of this defense established during terminal differentiation. During this complex process proliferating basal keratinocytes become suprabasally mitotically inactive and move through four epidermal layers (basal, spinous, granular and layer, stratum corneum) constantly adapting to the needs of the respective cell layer. As a result, squamous keratinocytes contain polymerized keratin intermediate filament bundles and a water‐retaining matrix surrounded by the cross‐linked cornified cell envelope (CE) with ceramide lipids attached on the outer surface. These cells are concomitantly insulated by intercellular lipid lamellae and hold together by corneodesmosmes. Many proteins essential for epidermal differentiation are encoded by genes clustered on chromosomal human region 1q21. These genes constitute the ‘epidermal differentiation complex’ (EDC), which is divided on the basis of common gene and protein structures, in three gene families: (i) CE precursors, (ii) S100A and (iii) S100 fused genes. EDC protein expression is regulated in a gene and tissue‐specific manner by a pool of transcription factors. Among them, Klf4, Grhl3 and Arnt are essential, and their deletion in mice is lethal. The importance of the EDC is further reflected by human diseases: FLG mutations are the strongest risk factor for atopic dermatitis (AD) and for AD‐associated asthma, and faulty CE formation caused by TG1 deficiency causes life‐threatening lamellar ichthyosis. Here, we review the EDC genes and the progress in this field.
Type 1 IFN‐induced protein MxA and plasmacytoid dendritic cells in lesions of morphea
Authors: Ghoreishi Mehran , Vera Kellet Cristián , Dutz Jan P.
Published: February 2012

Abstract:  Morphea is an autoimmune sclerotic skin disease of unknown pathogenesis. As type 1 interferons (IFN) have been implicated in the pathogenesis of systemic sclerosis, we proposed that type 1 IFN promote localized inflammation and fibrosis in morphea. To investigate the expression of the type 1 IFN‐inducible protein myxovirus A (MxA) and the presence of plasmacytoid dendritic cells (pDC) in lesions of morphea, lesional skin of 10 patients with morphea was examined by immunohistochemistry for the presence of the type 1 IFN‐inducible protein, myxovirus A (MxA), and the pDC markers, CD123 and BDCA‐2, and was compared with lesional skin of cutaneous lupus erythematosus, lichen planus and keloid. Lesional and non‐lesional morphea skin was compared. MxA was expressed in the epidermis as well as the reticular dermis and subcutis in morphea. pDCs were abundant around vessels and between fibrous bundles. Non‐lesional biopsies demonstrated little or no expression of MxA and pDC markers. Keloid showed minimal expression of MxA and pDC markers. We demonstrate the expression of type 1 IFN‐related protein MxA and plasmacytoid DCs in lesional but not in non‐lesional biopsies of morphea. These findings suggest a potential role for type 1 interferons in the pathogenesis of morphea.
Intrinsic DNA synthesis fidelity of xenotropic murine leukemia virus‐related virus reverse transcriptase
Authors: Barrioluengo Verónica , Wang Yi , Le Grice Stuart F. J. , Menéndez‐Arias Luis
Published: February 2012

Although recent reports have provided strong evidence to suggest that xenotropic murine leukemia virus‐related virus (XMRV) is unlikely to be the causative agent of prostate cancer and chronic fatigue syndrome, this recombinant retrovirus can nonetheless infect human cells in vitro and induce a chronic infection in macaques. In the present study, we determined the accuracy of DNA synthesis of the reverse transcriptases (RTs) of XMRV and Moloney murine leukemia virus (MoMLV) using a combination of pre‐steady‐state kinetics of nucleotide incorporation and an M13mp2‐based forward mutation assay. The results obtained were compared with those previously reported for the HIV type 1 BH10 strain (HIV‐1BH10) RT. MoMLV and XMRV RTs were 13.9 and 110 times less efficient [as determined by the catalytic rate constant of the nucleotide incorporation reaction (kpol)/equilibrium constant (Kd)] than the HIV‐1BH10 RT in incorporating correct nucleotides. Misinsertion and mispair extension kinetic studies demonstrated that MoMLV RT was more accurate than the HIV‐1BH10 RT. In comparison with the MoMLV RT, the XMRV RT showed decreased mispair extension fidelity and was less faithful when misincorporating C or A opposite A. However, the XMRV RT showed stronger selectivity against G in misinsertion fidelity assays. Forward mutation assays revealed that XMRV and MoMLV RTs had similar accuracy of DNA‐dependent DNA synthesis, but were > 13 times more faithful than the HIV‐1BH10 enzyme. The mutational spectra of XMRV and MoMLV RTs were similar in having a relatively higher proportion of frameshifts and transversions compared with the HIV‐1BH10 RT. However, the XMRV polymerase was less prone to introduce large deletions and one‐nucleotide insertions.
Silicateins, silicatein interactors and cellular interplay in sponge skeletogenesis: formation of glass fiber‐like spicules
Authors: Wang Xiaohong , Schloßmacher Ute , Wiens Matthias , Batel Renato , Schröder Heinz C. , Müller Werner E. G.
Published: February 2012

Biomineralization processes are characterized by controlled deposition of inorganic polymers/minerals mediated by functional groups linked to organic templates. One metazoan taxon, the siliceous sponges, has utilized these principles and even gained the ability to form these polymers/minerals by an enzymatic mechanism using silicateins. Silicateins are the dominant protein species present in the axial canal of the skeletal elements of the siliceous sponges, the spicules, where they form the axial filament. Silicateins also represent a major part of the organic components of the silica lamellae, which are cylindrically arranged around the axial canal. With the demosponge Suberites domuncula as a model, quantitative enzymatic studies revealed that both the native and the recombinant enzyme display in vitro the same biosilica‐forming activity as the enzyme involved in spicule formation in vivo. Monomeric silicatein molecules assemble into filaments via fractal intermediates, which are stabilized by the silicatein‐interacting protein silintaphin‐1. Besides the silicateins, a silica‐degrading enzyme silicase acting as a catabolic enzyme has been identified. Growth of spicules proceeds in vivo in two directions: first, by axial growth, a process that is controlled by evagination of cell protrusions and mediated by the axial filament‐associated silicateins; and second, by appositional growth, which is driven by the extraspicular silicateins, a process that provides the spicules with their final size and morphology. This radial layer‐by‐layer accretion is directed by organic cylinders that are formed around the growing spicule and consist of galectin and silicatein. The cellular interplay that controls the morphogenetic processes during spiculogenesis is outlined.
A lasting glow: Seizing the optimism of the Arab Spring
Authors: Powell Jonathan
Published: February 2012

Jonathan Powell predicts that we will see the seeds of the Arab Spring spreading across the Middle East, with regime change on the way in Syria and possibly even Iran. The west should not rule out intervention if there is local and regional support for military action.
Debate: Why aren't there more companies like John Lewis? The difficulties of breaking the stranglehold of shareholder capitalism
Authors: Mayfield Charlie , Purnell James , Davies Will
Published: February 2012

Charlie Mayfield, chair of the John Lewis Partnership, discusses different models of business ownership with James Purnell, chair of IPPR, and Will Davies, academic director of the Centre for Mutual and Employee‐Owned Business at the University of Oxford.
London falling?
Authors: Lammy David
Published: February 2012

In the wake of financial meltdown and riots in the streets, David Lammy asks whether London and its leaders have what it takes to restore confidence, cohesion and a collective sense of mission.
Disease distribution and characterisation of a new macluravirus associated with chirke disease of large cardamom
Authors: Mandal B. , Vijayanandraj S. , Shilpi S. , Pun K.B. , Singh V. , Pant R.P. , Jain R.K. , Varadarasan S. , Varma A.
Published: February 2012

Large cardamom (Amomum subulatum), an important spice crop grown in eastern sub‐Himalayan mountains of India, is affected by a viral disease commonly known as ‘chirke’, which is characterised by light and dark green streaks on the leaf lamina. Although chirke has been known to affect large cardamom for over 50 years, its distribution in large cardamom growing regions and aetiology have remained unaddressed. In this study for the first time, distribution of chirke in the major large cardamom growing regions in India has been determined. North Sikkim and eastern region of Darjeeling hills were endemic region with average disease incidence of 19.2–35%, whereas, Mirik region of Darjeeling hills were free from the disease. Suckers, the commonly used planting material, were the major source for spread of the disease. The virus was sap transmissible to the popular large cardamom cultivars Golsey, Ramsey, Swaney and Varlangey and vectored by Rhopalosiphum maidis and Myzus persicae in a non‐persistent manner. Flexuous virus particles measuring 625–650 × 12.5 nm were observed consistently associated with the diseased samples. Polyclonal antiserum to the purified virus showed serological affinity with a macluravirus, cardamom mosaic virus (CdMV) associated with a similar disease known as katte disease of small cardamom (Elettaria cardamomum) occurring in southern India. The 3′ terminal genome sequence (1776 nucleotides) of the virus was determined, which revealed a close sequence identity and phylogenetic relationships with the members of the genus Macluravirus. The deduced amino acid sequence of putative coat protein (CP) gene showed maximum similarity of 65.7% with the CdMV. Phylogenetic analysis based on CP and 3′ UTR showed that the virus was closer to Alpinia mosaic virus, CdMV and Chinese yam necrotic mosaic virus subclade. The results suggest that the virus associated with the chirke disease of large cardamom is a new species under the genus Macluravirus in the family Potyviridae for which the name large cardamom chirke virus (LCCV) is proposed.
Effect of Coffee Filtrate, Methylglyoxal, Glyoxal, and Caffeine on Salmonella Typhimurium and S. Enteritidis Survival in Ground Chicken Breasts
Authors: Maletta Anne B. , Were Lilian M.
Published: February 2012

Abstract:  The antimicrobial effect of roasted coffee filtrate (CF) and dicarbonyls on Salmonella Typhimurium and Salmonella Enteritidis in raw ground chicken breast meat (GCB) was investigated. Coffee was brewed and filtered before addition to GCB. Coffee filtrate with and without added caffeine, methylglyoxal, and/or glyoxal was added to GCB and then inoculated with Salmonella Typhimurium and Salmonella Enteritidis. Ground chicken samples were stomached with peptone water at days 1, 3, 5, and 7, plated on XLD agar with a TSA overlay, and Salmonella survivors were enumerated. CF alone gave less than a 1 Log reduction in all runs compared to control GCB with no treatment. Methylglyoxal (2.28 mg/g GCB) had the greatest antimicrobial effect against Salmonella Typhimurium and Salmonella Enteritidis in GCB with average Log reductions of 2.27 to 3.23, respectively, over the 7 d duration of the experiment compared to control GCB with no treatment. A 1 Log reduction was observed in GCB with CF, 0.93 mg glyoxal, and 1 mg caffeine/g chicken compared to the control and GCB with only CF. Heat‐produced coffee compounds could potentially reduce Salmonella in retail ground chicken and chicken products.
Inactivation of A. ochraceus Spores and Detoxification of Ochratoxin A in Coffee Beans by Gamma Irradiation
Authors: Kumar Sanjeev , Kunwar Amit , Gautam Satyendra , Sharma Arun
Published: February 2012

Abstract:  Ochratoxin A (OTA) produced in food by Aspergillus ochraceus is known to cause adverse health effects. Among the plantation products, green coffee beans are prone to fungal attack and get contaminated with OTA frequently. A fungal strain isolated from green coffee beans was characterized by morphological analyses as well as internal transcribed spacer (ITS) and 5.8S rDNA sequencing, turned out to be A. ochraceus, however, nontoxigenic. Hence, additional strains of A. ochraceus were procured and characterized for toxin production. Presterilized green coffee beans were spiked with a toxigenic strain and treated with gamma radiation. Minimum inhibitory dose (MID) of gamma radiation for 104 and 108 spores of A. ochraceus strain per 10 g of green coffee beans was found to be approximately 1 and approximately 2.5 kGy, respectively. The radiation treatment (10 kGy) almost degraded the preformed or in vitro added OTA (50 ppb) in coffee beans. OTA degradation was found to be enhanced with increase in moisture content. Cytotoxicity in terms of cell viability was found to be reduced significantly for radiation treated OTA in MTT [3‐(4,5‐dimethylthiazole‐2yl)‐2,5‐diphenyl tetrazolium bromide] assay as well as flow cytometric analysis when studied using human intestinal epithelial (Int‐407) cells. Similar finding was also observed with E. coli MG1655 cells. Thus the inclusion of gamma radiation treatment in the postharvest processing chain of green coffee beans could help in eliminating toxigenic fungi as well as destroying preformed OTA without affecting the sensory attributes.

Practical Application:  In general, mycotoxins including ochratoxin A (OTA) are highly stable to detoxifying agents. Green coffee beans are prone to fungal attack and could get frequently contaminated with the OTA due to improper drying or rehydration during storage. Gamma radiation processing of green coffee beans was found to eliminate the A. ochraceus spores as well as inactivate OTA without affecting its sensory attributes. Thus inclusion of gamma radiation in the postharvest processing chain of green coffee beans would be very useful for consumer safety and coffee trade.
β‐Casomorphin‐7 Cause Decreasing in Oxidative Stress and Inhibiting NF‐κB‐iNOS‐NO Signal Pathway in Pancreas of Diabetes Rats
Authors: Yin Hong , Miao Jinfeng , Ma Chang , Sun Guiju , Zhang Yuanshu
Published: February 2012

Abstract:  β‐Casomorphin‐7 (β‐CM‐7) is a milk biological active peptide. The present study is aimed to investigate the protective effects of β‐CM‐7, against oxidative stress in pancreas of streptozotocin‐induced diabetic rats by assaying malondialdehyde (MDA), nitric oxide (NO) level, the activity of enzymatic antioxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH‐Px), and NF‐κB, inducible nitric oxide synthase (iNOS) gene expression. A significant increase in the level of oxidative stress was observed in pancreas of the diabetic rats when compared to control rats. After 15 d oral administration of β‐CM‐7 (7.5 × 10−8mol/d), the pancreas MDA level was markedly reduced. Oral administration of β‐CM‐7 to diabetic rats showed an obviously increase in the activity of catalase in pancreas, oral administration of β‐CM‐7 to the diabetic group of rats also showed a reduction of NF‐κB and iNOS gene expression in pancreas. The elevated pancreas NO level was markedly reduced by the oral administration of β‐CM‐7. Thus, the results of the present study suggest that β‐CM‐7 may cause protective effects such as pronounced decreasing in oxidative stress and inhibiting NF‐κB‐iNOS‐NO signal pathway in pancreas of diabetes rats.
High management impact of Ga‐68 DOTATATE (GaTate) PET/CT for imaging neuroendocrine and other somatostatin expressing tumours
Authors: Hofman Michael S , Kong Grace , Neels Oliver C , Eu Peter , Hong Emily , Hicks Rodney J
Published: February 2012

Introduction: Ga‐68 DOTATATE (Ga‐octreotate, GaTate) positron emission tomography (PET)/CT has multiple advantages compared with conventional and In‐111 octreotide imaging for neuroendocrine tumours and other somatostatin‐receptor expressing tumours. This study assesses the management impact of incremental diagnostic information obtained from this technique compared with conventional staging.

Methods: Fifty‐nine GaTate PET/CT studies were performed over an 18‐month period (52 proven or suspected gastro‐entero‐pancreatic or bronchial neuroendocrine tumours and seven neural crest/mesenchymal tumours). A retrospective blinded review was performed on the number of abnormalities (1, 2–5 or >5) within defined regions with comparison to conventional imaging to assess incremental diagnostic information. Subsequent management impact (high, moderate or low) was determined by clinical review and follow up to assess pre‐PET stage, treatment intent and post‐PET management change.

Results: Eighty‐eight percent of GaTate studies were abnormal. Compared with conventional and In‐111 octreotide imaging, additional information was provided by GaTate PET/CT in 68 and 83% of patients, respectively. Management impact was high (inter‐modality change) in 47%, moderate (intra‐modality change) in 10% and low in 41% (not assessable in 2%). High management impact included directing patients to curative surgery by identifying a primary site and directing patients with multiple metastases to systemic therapy.

Conclusion: GaTate PET/CT imaging provides additional diagnostic information in a high proportion of patients with consequent high management impact. GaTate PET/CT could replace 1In‐111 octreotide scintigraphy at centres where it is available given its superior accuracy, faster acquisition and lower radiation exposure. Rapid implementation could be achieved by allowing substitutional funding in the Medicare Benefit Schedule.
Tubular breast carcinoma: An argument against treatment de‐escalation
Authors: Hansen Carmen J , Kenny Liz , Lakhani Sunil R , Ung Owen , Keller Jacqui , Tripcony Lee , Cheuk Robyn , Grogan Michelle , Vargas Ana Cristina , Martin Jarad
Published: February 2012

Purpose: To evaluate the role of adjuvant radiotherapy in management of patients with tubular carcinoma of the breast.

Methods: One hundred seventy‐eight patients treated for tubular carcinoma were identified from the Queensland Radium Institute database. A retrospective review of medical records identified 115 patients meeting eligibility criteria: breast‐conserving surgery for a histological diagnosis of tubular carcinoma, minimum follow up of 12 months and adequate medical records.

Results: Median follow up was 64 months. There were no significant differences between patient characteristics treated with and without radiotherapy. Median age at diagnosis was 54 (36–78) years. Ninety‐five percent tumours were T1 and four patients had positive axillary lymph nodes. Of 94 patients treated with adjuvant radiotherapy, one developed local relapse. Five of 21 patients who did not have adjuvant radiotherapy failed locally. Five‐year relapse‐free survival with and without radiotherapy was 100 and 89%, respectively (hazard ratio for radiotherapy: 0.06; 95% confidence interval 0.01–0.32, P = 0.001).

Conclusion: Radiotherapy has a significant impact on relapse‐free survival in patients treated with breast‐conserving surgery for tubular carcinoma.
Value of fused positron emission tomography CT in detecting primaries in patients with primary unknown cervical lymph node metastasis
Authors: Chen Yue‐Hong , Yang Xin‐Ming , Li Shi‐Sheng , Wang Yuan‐Hua , He Jian‐Jun , Yang Yi‐Da , Wang Shuang , Liu Jia‐Jia , Zhang Xiao‐Li
Published: February 2012

Objective: Identification of the primary tumour can prolong the life expectancy of patients with primary unknown cervical lymph node metastasis (PUCLNM) through targeted therapy. This study investigated the value of 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET‐CT) at identifying primaries in patients with PUCLNM.

Methods: Twenty‐seven patients (21 males and 6 females, median age 48.2 ± 16.3, age range 30–73) with PUCLNM underwent FDG PET‐CT to search for the primary tumour, which could not be detected by conventional diagnostic modalities. The results were analysed and correlated with either pathological findings or clinical follow up.

Results: Pathological FDG uptake suspicious for the primary was detected in 13 cases, while the primary tumour remained occult in 14 cases. Eleven of 13 patients with suspected primaries were confirmed by histological findings. One with a coexisting second tumour and three with unexpected distant metastases were found in patients with confirmed primaries. The most common primary location in patients with PUCLNM found in our study was nasopharynx. In those 14 patients with negative FDG PET‐CT results, only one patient had a primary malignancy that was proven histologically after endoscopy with biopsy during a period of clinical follow up. The sensitivity, specificity, accuracy and positive predictive values of FDG PET‐CT were 91.7, 86.7, 88.9 and 84.6%, respectively.

Conclusion: FDG PET‐CT is a useful tool to help search for unknown primaries in patients with cervical lymph node metastasis and has an acceptable diagnostic yield for the detection of distant malignancies.
Blindness of Johann Sebastian Bach
Authors: Tarkkanen Ahti
Published: February 2012

Johann Sebastian Bach (1685–1750) was one of the greatest composers of all time. Apart from performing as a brilliant organist, he composed over 1.100 works in almost every musical genre. He was known as a hardworking, deeply Christian person, who had to support his family of 20 children and many students staying at his home. At the age of 64 years, his vision started to decline. Old biographies claim that it was the result of overstressing his vision in poor illumination. By persuasion of his friends, he had his both eyes operated by a travelling British eye surgeon. A cataract couching was performed. After surgery, Bach was totally blind and unable to play an organ, compose or direct choirs and orchestras. He was confined to bed and suffering from immense pain of the eyes and the body. He died <4 months after surgery. In this paper, as the plausible diagnosis, intractable glaucoma because of pupillary block or secondary to phacoanaphylactic endophthalmitis is suggested.
Managing a Remanufacturing System with Random Yield: Properties, Observations, and Heuristics
Authors: Tao Zhijie , Zhou Sean X. , Tang Christopher S.
Published: February 2012

We study a remanufacturing system that involves the ordering of a serviceable product and the remanufacturing of multiple types of returned products (cores) into the serviceable product. In addition to random demand for the serviceable product and random returned quantities of different types of cores in each time period, the remanufacturing yield of each type of core is also uncertain. By analyzing a multi‐period stochastic dynamic program, we derive several properties of the optimal ordering/remanufacturing policy. In addition to some insights, these properties can be used to reduce the search effort of the optimal policy. We also demonstrate that some existing results derived from related models no longer hold in remanufacturing systems with random yield. Recognizing the optimal ordering/remanufacturing policy is highly complex, we examine three simple heuristics that can be efficiently solved and implemented in practice. Among these three heuristics, our numerical analysis suggests that the heuristic that captures most of the yield uncertainty and future system evolvement as well as some of the properties of the optimal ordering/remanufacturing policy outperforms the other two heuristics.
Continuous glucose monitoring system: Is it really accurate, safe and clinically useful?
Authors: Sato Junko , Hirose Takahisa , Watada Hirotaka
Published: February 2012

The continuous glucose monitoring system (CGM) has been used for constant checking of glucose level by measuring interstitial glucose concentrations, since the early days of the 21st century. It can potentially improve diabetes care if used carefully with the understanding of the characteristics of this system. Although there is a time lag of approximately 5–15 min between blood and interstitial glucose levels, the system is considered the most suitable device for meticulous glucose control and prevention of hypoglycemia. A large number of studies have examined its accuracy, safety and clinical effectiveness. The continuous glucose‐error grid analysis (CG‐EGA), designed by WL Clarke, evaluates the clinical accuracy of CGM. It examines ‘temporal’ characteristics of the data, analyzing pairs of reference and sensor readings as a process in time represented by a ‘bidimensional’ time series and taking into account inherent physiological time lags. Investment in CG‐EGA is clearly meaningful, even though there are other methodologies for evaluation. The use of each method complementarily is the most effective way to prove the accuracy of the device. The device has improved gradually, and real‐time CGM, which allows real‐time monitoring of blood glucose level, is already available commercially. The use of real‐time CGM could potentially lead to over‐ or undertreatment with insulin. Patient education through proper and effective handling of the new device is essential to improve diabetes care. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00197.x, 2012)
BaSTA: an R package for Bayesian estimation of age‐specific survival from incomplete mark–recapture/recovery data with covariates
Authors: Colchero Fernando , Jones Owen R. , Rebke Maren
Published: February 2012

1. Understanding age‐specific survival in wild animal populations is crucial to the study of population dynamics and is therefore an essential component of several fields including evolution, management and conservation.

2. We present Bayesian survival trajectory analysis (BaSTA), a free open‐source software package for estimating age‐specific survival from capture–recapture/recovery data under a Bayesian framework.

3. The method copes with low recapture probabilities, unknown ages (e.g. because of left‐truncation) and unknown ages at death (e.g. because of right‐censoring). It estimates survival and detection parameters as well as the unknown birth and death times (i.e. latent states) while allowing users to test a range of survival models. In addition, the effect of continuous or categorical covariates can be evaluated.

4. This tool facilitates the analysis of age patterns of survival in long‐term animal studies and will enable researchers to robustly infer the effect of covariates, even with large amounts of missing data.
Bats as bioindicators – the need of a standardized method for acoustic bat activity surveys
Authors: Stahlschmidt Peter , Brühl Carsten A.
Published: February 2012

1. The species‐rich group of bats fills a wide range of ecological niches and provides ecosystem services like pest control. Bats are known to be sensitive to environmental stressors and could, therefore, be used in assessing ecosystem quality. To use bats as bioindicators, a standardized bat survey method needs to be established as the existing approaches vary in their methodology, and results are, therefore, often not comparable.

2. Generally, there are two different acoustic bat survey methods: the transect walk and the stationary measurement. By conducting transect surveys and simultaneously using several stationary systems, we measured bat activity within a homogeneous habitat and evaluated which method assessed the spatial bat activity patterns with highest precision. Also the survey tool – the detectors themselves – can be grouped into devices with two different methods of triggering the recording of ultrasonic signals: actively by a fieldworker or automatically by a built‐in recording control algorithm of the detector. We measured bat activity simultaneously and side by side with both methods for direct comparison.

3. Our results indicate that the transect survey fails to represent the heterogeneous bat activity patterns in a homogeneous landscape. Furthermore, errors occur based on the subjective hearing of the active triggering of the data recording by the human operator.

4. The application of several stationary and automatic sampling systems has the highest potential for standardized acoustic bat surveys. The general use of such an approach would enable us to understand bat activity at landscape scale and could lead to an improvement of bats as bioindicators.
Mixed Convection Three-Dimensional Flow of an Upper-Convected Maxwell Fluid Under Magnetic Field, Thermal-Diffusion, and Diffusion-Thermo Effects
Authors: Hayat T. , Awais M. , Obaidat S.
Published: February 2012

This paper discusses the mixed convection three-dimensional boundary layer flow of upper-convected Maxwell fluid over a stretching surface. Magnetohydrodynamic (MHD) combined with Soret and Dufour effects are also taken into account. The governing problems are first modeled and then solved by a homotopy analysis method (HAM). The variations of several parameters of interest on the velocity, concentration, and temperature fields are analyzed by the presentation of graphs. Several known results have been pointed out as the particular cases of the present analysis.
182
W Evidence for Long-Term Preservation of Early Mantle Differentiation Products
Authors: Touboul Mathieu , Puchtel Igor S. , Walker Richard J.
Published: February 2012

Earth's Sluggish Past

Based on their affinity for iron or silicon, some elements partition into different compartments of Earth's interior. In the early stages of the formation of the solar system, when Earth was rapidly accreting and differentiating to form a core and mantle, elements such as tungsten and hafnium went along for the ride. By studying the signatures of these elements and their isotopes in ancient volcanic rocks from the mantle,

Touboul
et al.

(p.
1065
, published online 16 February; see the Perspective by

Bennett

) reveal that there was a long-lived
182
W reservoir that formed deep within Earth during the first 30 million years of the solar system. Because the reservoir persisted for over 1.7 billion years, it appears the mantle was poorly mixed and indeed it was so sluggish that it did not even homogenize during the massive collision that formed the Moon.
Lin28b Reprograms Adult Bone Marrow Hematopoietic Progenitors to Mediate Fetal-Like Lymphopoiesis
Authors: Yuan Joan , Nguyen Cuong K. , Liu Xiuhuai , Kanellopoulou Chrysi , Muljo Stefan A.
Published: February 2012

Making Immune Cells Young Again

Hematopoiesis, the development of the immune system, occurs in distinct waves. The immune system is first populated by cells that arise from fetal hematopoietic stem cells (HSCs) and then later by cells derived from adult HSCs. Furthermore, fetal HSCs give rise to lymphocytes with innate immunelike properties, whereas adult HSCs give rise to classical T and B cells.

Yuan
et al.

(p.
1195
, published online 16 February) now uncover the molecular mechanism behind these distinct waves of hematopoiesis. Expression of the RNA binding proteins Lin28 and Lin28b is enriched in fetal hematopoietic stem/progenitor cells (HSPCs) in mice and humans. Ectopic expression of Lin28 in mouse adult HSPCs was sufficient to induce the differentiation of both classical and innate-like lymphocyte lineages.
Observation of Quantum Criticality with Ultracold Atoms in Optical Lattices
Authors: Zhang Xibo , Hung Chen-Lung , Tung Shih-Kuang , Chin Cheng
Published: February 2012

Critically Cold Atoms

Unlike classical phase transitions, such as the freezing of water into ice, which is driven by lowering the temperature of the system, quantum phase transitions occur at absolute zero and are driven by other parameters, including magnetic field or pressure. In the vicinity of a quantum phase transition, a critical region forms where physical observables obey scaling laws as a consequence of the self-similarity of the system. Quantum phase transitions and quantum criticality are usually observed in solid state, but

Zhang
et al.

(p.
1070
, published online 16 February) used an optical lattice filled with a cold gas of atoms to simulate a quantum phase transition—from an insulator to a superflnuid in two dimensions. They observed the characteristic scaling of the equation of state, a finding that will facilitate the building of a platform in a tunable system for further investigations of quantum criticality.
Reengineering Device Translation Timelines
Authors: Watson John T.
Published: February 2012

Innovative engineering will substantially shorten the translational medicine timeline from concept to clinical application of medical devices.
Ovarian torsion among girls presenting with abdominal pain: a retrospective cohort study
Authors: McCloskey Kathleen , Grover Sonia , Vuillermin Peter , Babl Franz E
Published: February 2012

Background

Ovarian torsion (OT) is an important cause of abdominal pain in girls. Prompt recognition of OT may lead to higher rates of ovarian salvage.

Objective

To identify clinical and laboratory findings that may indicate OT among girls with abdominal pain.

Methods

Retrospective review of two cohorts of girls aged 5–17 years admitted to a children's hospital.Cohort 1:Girls admitted with abdominal pain from the emergency department (2008).Cohort 2:Girls with a discharge diagnosis of OT (2003–9).

Results

Cohort 1: 325 girls were admitted from the emergency department with abdominal pain during 2008. Of these, 9 (3%) were diagnosed with OT.Cohort 2:37 girls were diagnosed with OT during 2003–9. Clinical or laboratory features differentiating OT from all abdominal pain could not be identified. A comparison of girls admitted with confirmed appendicitis showed that OT was more likely to be associated with a mass (RR=4.2, 95% CI 1.1 to 17), and less likely to be associated with anorexia (RR=0.46, 95% CI 0.23 to 0.93), guarding (RR=0.53, 95% CI 0.34 to 0.85), an elevated C reactive protein (RR=0.32, 95% CI 0.14 to 0.83), or leucocytosis (RR=0.4, 95% CI 0.21 to 0.78). Findings were similar in girls with an admission diagnosis of ‘possible appendicitis’.

Conclusion

Clinical or laboratory features that would identify cases of OT among girls admitted with abdominal pain could not be identified. Some findings help to differentiate OT from appendicitis, but there is a large degree of overlap. OT is an uncommon condition, but has important management implications, and should be considered inallgirls presenting with abdominal pain.
Playground equipment injuries at home versus those in public settings: differences in severity
Authors: Keays Glenn , Skinner Robin
Published: February 2012

The objective of the present research was to compare the severity of playground-related injuries in backyards of home with those occurring in public settings. This case–control study used emergency-based surveillance data from Canada regarding children, 3–11 years old, who were injured after falling from playground equipment (PGE). Cases were those whose injuries occurred at home (backyards), and controls were those whose injuries occurred in parks, schools or daycare centres. Of the 39 730 subjects selected, 84% happened in public and 16% at home. Children falling from a home PGE had greater odds of severe injuries (OR=1.30; 95% CI 1.23 to 1.37) and fractures (OR=1.47; 95% CI 1.39 to 1.55) than those from public PGE. Children aged 3–5 years falling off slides at home, compared to slides in public settings, had the greatest odds of severe injuries (OR=1.72; 95% CI 1.41 to 2.09) and fractures (OR=2.17; 95% CI 1.79 to 2.64.) When setting up PGE at home, parents should be diligent in using proper landing surfaces, such as those found in public playgrounds.
INTRODUCTION
Authors: AZIZ-ALAOUI M. A. , BERTELLE CYRILLE , LIU XINZHI
Published: February 2012

One of the main characteristics of complexity is the emergence of properties due to dynamical processes. This special issue has put together a unique collection of articles written by leading researchers and experts around the globe on recent advances in complex systems and applications, in various fields of science and engineering. It focuses not only on equation-based modeling of eco- or bio-systems analysis but also on the study of eco- or bio-complexity and global emergent properties and self-organization, resulting from various interactions.