bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Responses of Antioxidative Defence System to Long‐Term Field Drought in Wheat (Triticum aestivum L.) Genotypes Differing in Drought Tolerance
Authors: Singh S. , Gupta A. K. , Kaur N.
Published: October 2011

Drought is a severe abiotic stress and the major constraint on wheat (Triticum aestivum L.) productivity world wide. Deciphering the mechanisms of drought tolerance is a challenging task because of the complexity of drought responses, environmental factors and their interactions. The objective of this study was to evaluate the ability of the antioxidative defence system in imparting tolerance against drought‐induced oxidative stress and yield loss in two wheat genotypes, when subjected to long‐term field drought. Drought resulted in an increase in H2O2 accumulation and lipid peroxidation and decrease in ascorbate level in roots and leaves at different plant developmental stages. Drought‐tolerant genotype having higher antioxidative enzymes activities, and ascorbate level was superior to that of sensitive genotype in maintaining lower H2O2 content and lipid peroxidation and higher growth, yield and yield components under water deficit. Various antioxidative enzymes showed positive correlation with ascorbate and negative with H2O2 content. In developing grains, antioxidative defence response was nearly similar among both the genotypes under control condition; however, sensitive genotype failed to modulate the activities of antioxidative enzymes according to the ROS rush under field drought. Poor capacity of the antioxidative defence system in vegetative and reproductive tissues of sensitive genotype seems to be responsible, at least partly, for reduced yield potential under water deficit.
Latitudinal trends in the species richness of free‐living marine nematode assemblages from exposed sandy beaches along the coast of Chile (18–42 °S)
Authors: Lee Matthew R. , Riveros Marcela
Published: October 2011

The latitudinal pattern of species richness of free‐living marine nematodes from exposed sandy beaches along the coast of Chile between 18 and 42° S was examined. Unlike many other examinations of latitudinal gradients, this study is not based on data mined from the literature, but on samples collected specifically to examine these themes. Five replicate quantitative 50 cm3samples of sediment were taken from the zone of retention of 66 exposed sandy beaches. The free‐living nematode fauna was identified and quantified to species level. The data were then examine using ordinary least squares and simultaneous autoregressive model (SARerr) regression methods, examining the associations between species richness and latitude, coastline complexity, and sea surface temperature, primary productivity of the adjacent coastal waters and mean latitudinal range size. The species richness of free‐living marine nematodes from exposed sandy beaches along the coast of Chile decreased with increasing latitude and was strongly associated with mean annual sea surface temperature. Mean latitudinal range size increased with increasing latitude, supporting Rapoport’s rule, and decreased with increasing species richness. The results suggest that the nematode fauna of exposed sandy beaches is derived from a low latitude fauna that has dispersed to higher latitudes, but that many species may be physiologically constrained, by temperature, from dispersing further south.
Chondroma of the dural convexity: A case report and literature review
Authors: Abeloos Laurence , Maris Calliope , Salmon Isabelle , Balériaux Danièle , Sadeghi Niloufar , Lefranc Florence
Published: October 2011

Chondromas are unusual tumors that arise from the base of the skull and have a predilection for the spheno‐ethmoidal region. Chondromas represent less than 0.5% of all intracranial tumors. In rare instances, these tumors originate from the dura mater of the convexity. Fewer than 30 cases of dural chondromas arising from the convexity or the falx are reported in the literature. In this study, we describe a new case of convexity chondroma. We discuss the radiological and histological features of this case and also review the literature.
Radiation damage to the lung: Mitigation by angiotensin‐converting enzyme (ACE) inhibitors
Authors: MEDHORA MEETHA , GAO FENG , JACOBS ELIZABETH R. , MOULDER JOHN E.
Published: October 2011

Concern regarding accidental overexposure to radiation has been raised after the devastating Tohuku earthquake and tsunami which initiated the Fukushima Daiichi nuclear disaster in Japan in March 2011. Radiation exposure is toxic and can be fatal depending on the dose received. Injury to the lung is often reported as part of multi‐organ failure in victims of accidental exposures. Doses of radiation >8 Gray to the chest can induce pneumonitis with right ventricular hypertrophy starting after ∼2 months. Higher doses may be followed by pulmonary fibrosis that presents months to years after exposure. Though the exact mechanisms of radiation lung damage are not known, experimental animal models have been widely used to study this injury. Rodent models for pneumonitis and fibrosis exhibit vascular, parenchymal and pleural injuries to the lung. Inflammation is a part of the injuries suggesting involvement of the immune system. Researchers worldwide have tested a number of interventions to prevent or mitigate radiation lung injury. One of the first and most successful class of mitigators are inhibitors of angiotensin‐converting enzyme (ACE), an enzyme that is abundant in the lung. These results offer hope that lung injury from radiation accidents may be mitigated, since the ACE inhibitor captopril was effective when started up to 1 week after irradiation.
Historical vignette: Dr Charles Robson; Pioneer Canadian Pediatric Anesthetist
Authors: Steward David J.
Published: October 2011

Charles Robson (Figure 1) was born in New Westminster, British Columbia (now a suburb of Vancouver), in 1884 and graduated in medicine from McGill University in Montreal in 1913. Having interned and with some anesthesia training at the Royal Victoria Hospital in Montreal, he was sent overseas to work in a Canadian Army Hospital where he founded a school to train military anesthetists. Returning to Canada in 1919, he joined the staff of the Hospital for Sick Children in Toronto as chief anesthetist, a position he held until 1951 (1). During most of this time, he was the sole full‐time anesthetist at the hospital; administration of anesthesia at this hospital was not limited to staff anesthetists until 1950 (1).

 Dr Charles Robson.

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Large losses of inorganic nitrogen from tropical rainforests suggest a lack of nitrogen limitation
Authors: Brookshire E. N. J. , Gerber Stefan , Menge Duncan N. L. , Hedin Lars O.
Published: October 2011

Ecology Letters (2011) 14: 9–16

Inorganic nitrogen losses from many unpolluted mature tropical forests are over an order of magnitude higher than losses from analogous temperate forests. This pattern could either reflect a lack of N limitation or accelerated plant–soil N cycling under tropical temperatures and moisture. We used a simple analytical framework of the N cycle and compared our predictions with data of N in stream waters of temperate and tropical rainforests. While the pattern could be explained by differences in N limitation, it could not be explained based on up‐regulation of the internal N cycle without invoking the unlikely assumption that tropical plants are two to four times less efficient at taking up N than temperate plants. Our results contrast with the idea that a tropical climate promotes and sustains an up‐regulated and leaky – but N‐limited – internal N cycle. Instead, they are consistent with the notion that many tropical rainforests exist in a state of N saturation.
Soluble activin receptor type IIB treatment does not cause fat loss in mice with diet‐induced obesity
Authors: McPherron A. C. , Guo T. , Wang Q. , Portas J.
Published: October 2011

The growth factor myostatin (MSTN) negatively regulates skeletal muscle mass. Mstn gene deletion in mice causes increased muscle mass, reduced adiposity and resistance to genetic or diet‐induced obesity (DIO). Pharmacologic MSTN inhibition in mice also causes increased muscle mass and resistance to DIO. To test whether MSTN inhibition causes weight loss in mice that are already obese, we inhibited MSTN in mice fed a high‐fat diet (HFD). Mice were fed a diet containing 60% kcal from fat for 12 weeks followed by treatment with a soluble MSTN receptor derived from the activin receptor type IIB extracellular domain. During the next 12 weeks of soluble receptor treatment and HFD feeding, lean mass increased without a loss of adipose mass. Glucose metabolism was also similar between groups. Our results suggest that MSTN inhibition may be ineffective at inducing weight loss in obese patients.
Blockade of kinin B1 receptor reverses plasma fatty acids composition changes and body and tissue fat gain in a rat model of insulin resistance
Authors: Dias J. P. , Couture R.
Published: October 2011

Aim: Kinin B1 receptor (B1R) contributes to insulin resistance through a mechanism involving oxidative stress. This study examined the effect of B1R blockade on the changes in plasma fatty acids composition, body and tissue fat mass and adipose tissue inflammation that influence insulin resistance.

Methods: Sprague–Dawley rats were fed with 10% D‐glucose or tap water (Control) for 13 weeks and during the last week, rats were administered the B1R antagonist SSR240612 (10 mg/kg/day, gavage) or vehicle. The following parameters were assessed: plasma fatty acids (by gas chromatography), body composition (by EchoMRI), metabolic hormone levels (by radioimmunoassay), expression of B1R and inflammatory markers in adipose tissue (by Western blot and qRT‐PCR).

Results: Glucose feeding significantly increased plasma levels of glucose, insulin, leptin, palmitoleic acid (16:1n‐7), oleic acid (18:1n‐9), Δ6 and Δ9 desaturases while linoleic acid (18:2n‐6), arachidonic acid (20:4n‐6) and Δ5 desaturase were decreased. SSR240612 reduced plasma levels of insulin, glucose, the homeostasis model assessment index of insulin resistance, palmitoleic acid and n‐7 family. Alterations of Δ5, Δ6 and Δ9 desaturases were normalized by SSR240612. The B1R antagonist also reversed the enhancing effect of glucose feeding on whole body and epididymal fat mass and on the expression of macrophage CD68, interleukin‐1β, tumour necrosis factor‐α and inducible nitric oxide synthase in retroperitoneal adipose tissue. B1R protein and mRNA were not detected in retroperitoneal adipose tissue.

Conclusion: Insulin resistance in glucose‐fed rats is associated with low state inflammation in adipose tissue and plasma fatty acids changes which are reversed by B1R blockade. These beneficial effects may contribute to insulin sensitivity improvement and the prevention of obesity.
Validation of DN4 as a screening tool for neuropathic pain in painful diabetic polyneuropathy
Authors: Spallone V. , Morganti R. , D’Amato C. , Greco C. , Cacciotti L. , Marfia G. A.
Published: October 2011

Diabet. Med. 29, 578–585 (2012)

Aims  DN4 (Douleur Neuropathique en 4 Questions) is a screening tool for neuropathic pain consisting of interview questions (DN4‐interview) and physical tests. It has not formally been validated in diabetes. We evaluated the validity and diagnostic accuracy of DN4 and DN4‐interview in identifying neuropathic pain of painful diabetic polyneuropathy.

Methods  In 158 patients with diabetes, the presence of diabetic polyneuropathy and neuropathic pain was assessed using scoring system for symptoms and signs, quantitative sensory testing, nerve conduction studies, pain history, numerical rating scale, and Short‐Form McGill Pain Questionnaire. Painful diabetic polyneuropathy was defined as the presence of diabetic polyneuropathy plus chronic neuropathic pain in the same area as neuropathic deficits. A blinded investigator performed DN4.

Results  The DN4 score was significantly related to all the neurological and electrophysiological measurements and to Short‐Form McGill Pain Questionnaire (ρ = 0.58, P < 0.0001). DN4 and DN4‐interview scores showed a high diagnostic accuracy for painful diabetic polyneuropathy with areas under the receiver operating characteristic curve of 0.94 and 0.93, respectively. At the cut‐off of 4, DN4 displayed sensitivity of 80%, specificity of 92%, positive predictive value (PPV) of 82%, negative predictive value (NPV) of 91%, and likelihood ratio for a positive result (LR+) of 9.6. At the cut‐off of 3, DN4‐interview showed sensitivity and specificity of 84%, PPV of 71%, NPV of 92%, and LR+ of 5.3.

Conclusions  This is the first validation study of DN4 for painful diabetic polyneuropathy, which supports its usefulness as both a screening tool for neuropathic pain in diabetes and a reliable component of the diagnostic work up for painful diabetic polyneuropathy.
The Sacred Kingdom and the Royal Wedding of 2011
Authors: BONNEY NORMAN
Published: October 2011

Despite secularisation and increased religious diversity the UK state and the monarchy are religiously legitimated institutions which have their origins in protestant/catholic divisions over three hundred years ago but which remain strong enough to survive in the current era. The Church of England acts not only as the established church of England but as a church for the UK with respect to events such as the coronation and the royal wedding of 2011. Ecumenical and interfaith initiatives have been attempted by the government and the monarchy and were evident in attendance at the wedding but it demonstrated the ritual supremacy of the state church and the inevitable difficulties of seeking to achieve formal representation for religious diversity in the state. Attempts at more formally inclusive religious involvement in state institutions conflict with other goals such as gender equity and suggest that secular state institutions might be fairer to all religions, denominations and those with no beliefs.
The Government's Plans for Decentralisation and Localism: A Progress Report
Authors: CROWE JESSICA
Published: October 2011

This article assesses progress on the coalition government's ambitious agenda for decentralisation and localism against six actions set out in the government's own guide to decentralisation. It critically examines the government's case that the previous government's centralised approach failed. The six actions cover reducing bureaucracy, community empowerment, more local control of public funding, provider diversification, more public scrutiny and stronger local accountability. The paper concludes that accountability is the most challenging and that progress is hampered by tensions between the actions and between government departments. It argues that the government needs a clearer, shared vision for localism going forward.
Mexico's Business Cycles and Synchronization with the USA in the Post‐NAFTA Years
Authors: Miles William , Vijverberg Chu‐Ping C.
Published: October 2011

A number of papers have investigated the increasing macroeconomic ties between Mexico and the USA. These studies have relied on linear models, however, making their results suspect. Other papers have investigated nonlinearity over the Mexican business cycle, but have not studied the links between the Mexican and US economies. In this paper a Markov‐switching model is employed to investigate the changing macroeconomic effect of the USA on Mexico. The findings show that the USA indeed appears to have a much larger impact since the passage of the North Atlantic Free Trade Association (NAFTA) than in previous years. Results also indicate that the level of foreign exchange reserves has much less predictive power for the Mexican economy since NAFTA. This suggests that the greater synchronization with the US business cycle may be more attributable to better macroeconomic management in Mexico than to the closer trade links.
Exchange Rates and Stock Prices in the MENA Countries: What Role for Oil?
Authors: Chortareas Georgios , Cipollini Andrea , Eissa Mohamed Abdelaziz
Published: October 2011

This paper considers the linkage between stock prices and exchange rates in four MENA (Middle East and North Africa) emerging markets. In contrast to the existing evidence that uses a global market index to uncover such a relationship it is found that for the sample countries oil prices emerge as the dominant factor in the above relationship. The paper considers the presence of regime shifts and evidence is found of cointegration only for the period following the 1999 oil price shock. Readjustment towards equilibrium in each stock market occurs via oil price changes. Finally, a number of robustness checks are performed and persistence profiles produced.
Is there Complete, Partial, or No Recovery from Childhood Malnutrition? – Empirical Evidence from Indonesia*
Authors: Mani Subha
Published: October 2011

This article uses a dynamic panel data model to identify the impact of early nutritional deficiencies on individuals’ health status in later ages. We find that poor nutrition at young ages causes some, but not severe retardation in the growth of future height indicating partial recovery from chronic malnourishment. The results also indicate that – younger children, stunted children, and children who live in communities with six or more health posts exhibit larger recovery. The estimation strategy used here is especially attractive as it relies on weaker stochastic assumptions compared to earlier work in the literature.
Increased levels of COX‐2 in oral lichen planus supports an autoimmune cause of the disease
Authors: Danielsson K. , Ebrahimi M. , Wahlin Y.B. , Nylander K. , Boldrup L.
Published: October 2011

Background  Oral lichen planus (OLP) is a chronic inflammatory disease for which the pathogenesis is not fully understood. OLP has autoimmune features and auto immunity has been suggested as a potential cause, whereas WHO has classified OLP as a premalignant condition. Association between chronic inflammation and cancer is known and chronic inflammation is one of the characteristics of OLP. A protein connected to inflammation and suggested to be involved in cancer development is cyclooxygenase‐2 (COX‐2) which can be inhibited by microRNA‐26b (miR‐26b).

Objective  The aim was to map levels of COX‐2 and miR‐26b in OLP lesions to see if there was any correlation between expression of COX‐2 and its regulator miR‐26b in OLP.

Methods  In biopsies from 20 OLP patients and 20 age and gender‐matched controls laser‐ micro dissection of epithelium was performed. Quantitative RT‐PCR, immunohistochemistry and Western blot were used in the analysis.

Results  Levels of COX‐2 mRNA were significantly higher while levels of miR‐26b were significantly lower in OLP lesions compared to controls. Using immunohistochemistry normal oral mucosa samples did not show any expression of COX‐2 while OLP samples expressed the protein. No COX‐2 protein was detectable with Western blot.

Conclusion  Increased expression of COX‐2 and decreased expression of miR‐26b in OLP suggests both to play a role in OLP. COX‐2 has been connected to both malignant development and autoimmunity but as malignant development of OLP is quite rare we suggest that the increased levels of COX‐2 seen here support an autoimmune cause of the disease.
Routine FDG PET‐CT in patients with a high‐risk localized melanoma has a high predictive positive value for nodal disease and high negative predictive value for the presence of distant metastases
Authors: Wagner T. , Chevreau C. , Meyer N. , Mourey L. , Courbon F. , Zerdoud S.
Published: October 2011

Background  FDG PET‐CT is the superior imaging modality for the detection of visceral metastases (M+) in patients with melanoma. Conflicting evidence exists regarding its role for the initial staging of patients with high risk localized melanoma (large Breslow Thickness (BT) and/or ulceration).

Objective  To assess the role of routine staging with FDG PET‐CT in melanoma patients with localized high risk melanoma.

Methods  Forty‐eight consecutive patients with 1 < BT < 4 mm with ulceration and with BT ≥ 4 mm were staged with PET‐CT. PET‐CT procedures were performed on a GE Discovery ST® scanner. PET‐CT findings for regional nodal status and presence of distant metastatic disease were collected. The gold standard for nodal assessment was pathological examination. The gold standard for M+ was conventional imaging and clinical follow‐up, confirmed by biopsy whenever feasible.

Results  No patient had a positive PET‐CT for M+. Six patients (13%) had a non‐conclusive PET‐CT; none of them presented with M+ within 6 months. Forty‐three patients (90%) had a negative PET‐CT, amongst them only one patient (2.5%) presented with M+ within a year. Six patients had FDG‐avid lymph nodes in the drainage territory of the primary melanoma, either SLNB or lymph node dissection confirmed metastatic nodal involvement. The predictive positive value of PET for regional node involvement was 100%.

Comments  FDG PET‐CT does not seem to be effective at detecting M+ at baseline staging in patients with high risk localized melanoma. However, it has a high negative predictive value for the presence of M+ at 6 months and a high positive predictive value for nodal involvement.
Cutaneous adverse drug reactions to allopurinol: 10 year observational survey of the dermatology department – Cagliari University (Italy)
Authors: Atzori L. , Pinna A.L. , Mantovani L. , Ferreli C. , Pau M. , Mulargia M. , Aste N.
Published: October 2011

Background  Allopurinol is extensively prescribed for conditions associated with urate excess, despite being responsible for severe cutaneous adverse drug reactions (ADR).

Objective  A cross‐sectional survey of allopurinol cases observed at the main Dermatology Department with inpatients facilities in southern Sardinia. (approx 560 836 inhabitants).

Material and methods  Data collection of all consecutive patients referred for ADR between 2001 and 2010. Causality assessment followed the WHO Collaborating Centre for Drug Monitoring criteria; illness severity score was adopted for toxic epidermal necrolysis (SCORTEN).

Results  Allopurinol was the culprit drug in 84 of 780 cutaneous ADR cases (10.7%; 8.4 cases/year). Mean age was 74 years, 58% of the patients were female, 95% of patients required hospitalization. Clinical forms were maculo‐papular eruptions (34 cases), Stevens‐Johnson Syndrome/Toxic Epidermal Necrolysis (31 cases), vasculitis (six cases), Drug Rash Eosinophilia and Systemic Symptoms (DRESS) (three cases), Acute Generalized Exanthematous Pustolosis (AGEP) (three cases), Pityriasis rosea‐like eruption (three cases), lichenoid dermatitis (two cases), fixed drug eruption (one case), erythroderma (one case). The indication for allopurinol prescription was asymptomatic hyper‐uricemia in 95% of the patients. Twelve patients were under allopurinol dosage adjustment according to creatinine clearance. Final causality assessment was definite for 12% of the cases and probable for the remaining 88%. Full recovery was achieved in 88% of subjects; ten SJS/TEN patients died (12% overall mortality; 32% mortality of the SJS/TEN cases).

Conclusion  Considering the populations size of Southern Sardinia, is plausible that 1.5/100 000 Sardinian will be affected by allopurinol related ADR per year. Advanced age, and inappropriate allopurinol prescription were the main conditions affecting morbidity and mortality.
Is diet segregation between dabbling ducks due to food partitioning? A review of seasonal patterns in the Western Palearctic
Authors: Brochet A.‐L. , Dessborn L. , Legagneux P. , Elmberg J. , Gauthier‐Clerc M. , Fritz H. , Guillemain M.
Published: October 2011

Within the paradigm of resource‐limited competition‐structured communities, dabbling ducks (Anas spp.) have been used as a textbook example of how morphological differences, notably bill lamellar density and body length, may allow sympatric species to partition food and hence coexist. We reviewed all accessible diet studies from the Western Palearctic for three closely related dabbling duck species, mallard (Anas platyrhynchos), pintail (A. acuta) and teal (A. crecca), and present a comprehensive list of the food items (invertebrates, seeds, vegetative parts of plants) ingested. To assess the circumannual perspective of niche separation, we evaluated size distribution of ingested seeds among seasons and duck species. There was a significant difference among duck species in mean size and mass of ingested seeds, as well as in diet composition, with the largest seeds consumed by the largest species (mallard) with the coarsest bill filter apparatus (lamellae), and the smallest seeds by the smallest species (teal) with the finest bill lamellae. However, no effect of season was found, suggesting consistent diet segregation among species throughout the annual cycle of ducks and over large geographical areas. We argue that the patterns of food size separation between the three species are compatible with the idea of coexistence under interspecific competition.
Myo‐inositol hexakisphosphate, isolated from female gametophyte tissue of loblolly pine, inhibits growth of early‐stage somatic embryos
Authors: Wu Di , Cameron Sullards M. , Oldham Charlie D. , Gelbaum Les , Lucrezi Jacob , Pullman Gerald S. , May Sheldon W.
Published: October 2011

Myo‐inositol hexakisphosphate (InsP6), abundant in animals and plants, is well known for its anticancer activity. However, many aspects of InsP6 function in plants remain undefined. We now report the first evidence that InsP6 can inhibit cellular proliferation in plants under growth conditions where phosphorus is not limited.

A highly anionic molecule inhibitory to early‐stage somatic embryo growth of loblolly pine (LP) was purified chromatographically from late‐stage LP female gametophytes (FGs), and then characterized structurally using mass spectrometry (MS) and nuclear magnetic resonance (NMR) analyses.

Exact mass and mass spectrometry‐mass spectrometry (MS‐MS) fragmentation identified the bioactive molecule as an inositol hexakisphosphate. It was then identified as the myo‐isomer (i.e. InsP6) on the basis of 1H‐, 31P‐ and 13C‐NMR, 1H‐1H correlation spectroscopy (COSY), 1H‐31P heteronuclear single quantum correlation (HSQC) and 1H‐13C HSQC. Topical application of InsP6 to early‐stage somatic embryos indeed inhibits embryonic growth.

Recently evidence has begun to emerge that InsP6 may also play a regulatory role in plant cells. We anticipate that our findings will help to stimulate additional investigations aimed at elucidating the roles of inositol phosphates in cellular growth and development in plants.
Understanding niche shifts: using current and historical data to model the invasive redlegged earth mite, Halotydeus destructor
Authors: Hill Matthew P. , Hoffmann Ary A. , Macfadyen Sarina , Umina Paul A. , Elith Jane
Published: October 2011

Aim  Niche conservatism is key to understanding species responses to environmental stress such as climate change or arriving in new geographical space such as biological invasion. Halotydeus destructor is an important agricultural pest in Australia and has been the focus of extensive surveys that suggest this species has undergone a niche shift to expand its invasive range inland to hotter and drier environments. We employ modern correlative modelling methods to examine niche conservatism in H. destructor and highlight ecological differences between historical and current distributions.

Location  Australia and South Africa.

Methods  We compile comprehensive distribution data sets for H. destructor, representing the native range in South Africa, its invasive range in Australia in the 1960s (40 yr post‐introduction) and its current range in Australia. Using MAXENT, we build correlative models and reciprocally project them between South Africa and Australia and investigate range expansion with models constructed for historical and current data sets. We use several recently developed model exploration tools to examine the climate similarity between native and invasive ranges and subsequently examine climatic variables that limit distributions.

Results  The invasive niche of H. destructor in Australia transgresses the native niche in South Africa, and the species has expanded in Australia beyond what is predicted from the native distribution. Our models support the notion that H. destructor has undergone a more recent range shift into hotter and drier inland areas of Australia since establishing a stable distribution in the 1960s.

Main conclusions  Our use of historical and current data highlights that invasion is an ongoing dynamic process and demonstrates that once a species has reached an established range, it may still expand at a later stage. We also show that model exploration tools help understand factors influencing the range of invasive species. The models generate hypotheses about adaptive shifts in H. destructor.
Biased signalling and allosteric machines: new vistas and challenges for drug discovery
Authors: Kenakin Terry P
Published: October 2011

Seven transmembrane receptors (7TMRs) are nature's prototype allosteric proteins made to bind molecules at one location to subsequently change their shape to affect the binding of another molecule at another location. This paper attempts to describe the divergent 7TMR behaviours (i.e. third party allostery, receptor oligomerization, biased agonism) observed in pharmacology in terms of a homogeneous group of allosteric behaviours. By considering the bodies involved as a vector defined by a modulator, conduit and guest, these activities can all be described by a simple model of functional allostery made up of the Ehlert allosteric model and the Black/Leff operational model. It will be shown how this model yields parameters that can be used to characterize the activity of any ligand or protein producing effect through allosteric interaction with a 7TMR.

LINKED ARTICLES This article is part of a themed section on the Molecular Pharmacology of G Protein‐Coupled Receptors (GPCRs). To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐6. To view the 2010 themed section on the same topic visit http://onlinelibrary.wiley.com/doi/10.1111/bph.2010.159.issue‐5/issuetoc
The Peridural Membrane of the Spinal Canal: A Critical Review
Authors: Ansari Saeed , Heavner James E. , McConnell Douglas J. , Azari Hassan , Bosscher Hemmo A.
Published: October 2011

Abstract:  There exists substantial evidence that a peridural membrane (PM) is present in the spinal canal of humans and, like the pleura and peritoneum, has one or more physiologic functions. Innervation of the PM suggests that it may become a source of pain if injured. Although debated, the physiology of this structure has important implications with respect to neuraxial distribution of drugs and for back and radiating pain. This review, separated into embryological, anatomic, and physiologic discussions, provides an in‐depth summary of the observations of this connective tissue. The discrepancies between accounts are highlighted within each section. Focused research to clearly elucidate the true nature of the PM, especially as related to neuraxial distribution of drugs and back and radiating pain, is warranted.▪
Reason for clozapine cessation
Authors: Pai N. B. , Vella S. C.
Published: October 2011

Pai NB, Vella SC. Reason for clozapine cessation.

Objective:  Approximately 30% of individuals diagnosed with schizophrenia suffer from treatment‐resistant or refractory schizophrenia. The gold standard for treatment of refractory schizophrenia is clozapine. However, a significant number of patients cease clozapine therapy; therefore this study explores patient’s motives for cessation.

Method:  The motives for cessation and duration of clozapine treatment from a retrospective database of 151 patients with schizophrenia or schizo‐affective disorder who had ceased clozapine once or more were reviewed, with the motives for cessation coded. The general motives for cessation were non‐compliance, own decision, medical, poor response and other. In addition, the medical reasons for cessation were further codified: cardiac complications, neutropenia, fevers, other side effects and pregnancy.

Results:  The majority of patients ceased clozapine owing to non‐compliance with medical protocols or citing their own decision. Approximately half ceased after a period of 6 months or less. Seventeen per cent of patients ceased owing to medical reasons, with the largest proportions discontinuing treatment because of other side effects or neutropenia.

Conclusion:  Future research should seek to further investigate why patients decide to be non‐compliant and formulate their own decision to cease treatment, as this will facilitate strategies to promote adherence amongst these two groups that are potentially the most amenable to change.
Family history and oral health: findings from the Dunedin Study
Authors: Shearer Dara M. , Thomson W. Murray , Caspi Avshalom , Moffitt Terrie E. , Broadbent Jonathan M. , Poulton Richie
Published: October 2011

Shearer DM, Thomson WM, Caspi A, Moffitt TE, Broadbent JM, Poulton R. Family history and oral health: findings from the Dunedin Family History Study. Community Dent Oral Epidemiol 2011. © 2011 John Wiley & Sons A/S

Abstract – Context: The effects of the oral health status of one generation on that of the next within families are unclear.

Objectives: To determine whether parental oral health history is a risk factor for oral disease.

Methods: Oral examination and interview data were collected during the age‐32 assessments in the Dunedin Study. Parental data were also collected on this occasion. The sample was divided into two familial‐risk groups for caries/tooth loss (high risk and low risk) based on parents’ self‐reported history of tooth loss at the age‐32 assessment interview.

Main outcome measures: Probands’ dental caries and tooth loss status at age 32, together with lifelong dental caries trajectory (age 5–32).

Results: Caries/tooth loss risk analysis was conducted for 640 proband‐parent groups. Reference groups were the low‐familial‐risk groups. After controlling for confounding factors (sex, episodic use of dental services, socio‐economic status and plaque trajectory), the prevalence ratio (PR) for having lost 1+ teeth by age 32 for the high‐familial‐risk group was 1.41 [95% confidence interval (CI) 1.05, 1.88] and the rate ratio for DMFS at age 32 was 1.41 (95% CI 1.24, 1.60). In the high‐familial‐risk group, the PR of following a high caries trajectory was 2.05 (95% CI 1.37, 3.06). Associations were strongest when information was available about both parents’ oral health. Nonetheless, when information was available for one parent only, associations were significant for some outcomes.

Conclusions: People with poor oral health tend to have parents with poor oral health. Family/parental history of oral health is a valid representation of the intricacies of the shared genetic and environmental factors that contribute to an individual’s oral health status. Associations are strongest when data from both parents can be obtained.
Reassessment at 6–7 years of age of a randomized controlled trial initiated before birth to prevent early childhood caries
Authors: Plutzer Kamila , John Spencer A. , Keirse Marc J. N. C.
Published: October 2011

Plutzer K, Spencer AJ, Keirse MJNC. Reassessment at 6–7 years of age of a randomized controlled trial initiated before birth to prevent early childhood caries. Community Dent Oral Epidemiol 2012; 40: 116–124. © 2011 John Wiley & Sons A/S

Abstract –  Objectives:  To assess whether the effect of providing mothers with guidance during pregnancy and when the child was 6 and 12 months old, which had drastically reduced the prevalence of early childhood caries at 20 months of age, would be sustained at 6–7 years of age.

Methods:  Children, whose mothers had been enrolled in a randomized controlled trial during pregnancy and a comparison group of similar school children, were examined for the presence of caries by the South Australian School Dental Services (SA SDS) at 6–7 years of age.

Results:  Of 625 eligible trial participants, 277 (44%) participated in the follow‐up and dental records were available for 187 of them (30%). Loss to follow‐up and reasons for it were similar in the intervention and control groups. At 6–7 years of age, 33% of children in the trial had caries compared with 42% in the SA SDS comparison group (n = 263). All measures of caries severity (d3mft, d3mfs and SiC30) were lower, but not significantly so, in the intervention than in the control group. Children in the comparison group of school children had more severe caries than those in the trial (P < 0.01) and in the intervention group especially (P < 0.005). Children in both randomized groups suffered significantly less toothache than those in the comparison group (P < 0.001).

Conclusions:  Providing new mothers with guidance on caries prevention helps to reduce early childhood caries and has a sustainable effect up to school age.
Caries in adolescence – influence from early childhood
Authors: Alm A. , Wendt L. K. , Koch G. , Birkhed D. , Nilsson M.
Published: October 2011

Alm A, Wendt LK, Koch G, Birkhed D, Nilsson M. Caries in adolescence – influence from early childhood. Community Dent Oral Epidemiol 2012; 40: 125–133. © 2011 John Wiley & Sons A/S

Abstract –  Objective:  To analyse the relationship between caries determinants in early childhood and caries prevalence in proximal surfaces in adolescents at the age of 15 years.

Methods:  The present longitudinal study is part of a series of surveys of oral health in 671 children followed from 1 to 15 years of age. Data were selected from examinations, interviews and questionnaires at 1, 3 and 6 years and bitewing radiographs at 15 years of age. Uni‐ and multivariable logistic regression analyses were performed to identify caries‐related determinants. The outcome variable was carious lesions and fillings (DFa) in approximal tooth surfaces at 15 years of age. Statistical comparisons were made between caries‐free teenagers, DFa = 0 and teenagers with DFa > 0, DFa ≥ 4 and DFa ≥ 8, respectively.

Results:  In the final logistic regression analyses, caries experience at 6 years and mother’s self‐estimation of her oral health care as being less good to poor remained statistically significant and were related to caries in all three caries groups (i.e. DF > 0, ≥4 and ≥8) at 15 years of age. The consumption of sweets at 1 year remained statistically significant, with a caries experience of DF ≥ 4 and ≥ 8. The variables ‘parents born abroad’ and female gender were statistically significantly associated with DFa ≥ 4 and DFa ≥ 8, respectively. Furthermore, infrequent toothbrushing habits at 3 years of age and failure to attend the examination at 1 year were statistically significantly associated with caries at 15 years in the univariable analyses.

Conclusion:  Early caries experience, consumption of sweets at an early age and mother’s self‐estimation of her oral health care as being less good to poor are associated with approximal caries in adolescents. The study indicates that caries determinants identified during early childhood have a strong impact on approximal caries in adolescence.
A European Core Curriculum in Cariology: the knowledge base
Authors: Anderson P. , Beeley J. , Monteiro P. Manarte , de Soet H. , Andrian S. , Amaechi B. , Huysmans M.‐C. D. N. J. M.
Published: October 2011

This paper is part of a series of papers towards a European Core Curriculum in Cariology for undergraduate dental students. The European Core Curriculum in Cariology is the outcome of a joint workshop of the European Organization for Caries Research (ORCA) together with the Association for Dental Education in Europe (ADEE), which was held in Berlin from 27 to 30 June 2010. This paper presents a closer look at the knowledge base as presented in the European Core Curriculum in Cariology. It comprises not only traditional basic sciences, such as anatomy and histology, but also emerging sciences such as molecular biology and nanotechnology and also fields such as behavioural sciences and research methodology. The different supporting competences are elaborated and explained. The problems of implementing a curriculum that truly integrates this foundation knowledge into the clinical teaching are discussed.
Decision‐making and preventive non‐surgical therapy in the context of a European Core Curriculum in Cariology
Authors: Bottenberg P. , Ricketts D. N. J. , Van Loveren C. , Rahiotis C. , Schulte A. G.
Published: October 2011

This paper is part of a series of papers towards a European Core Curriculum in Cariology for undergraduate dental students. The European Core Curriculum in Cariology is the outcome of a joint workshop of the European Organisation for Caries Research (ORCA) together with the Association for Dental Education in Europe (ADEE), which was held in Berlin from 27 to 30 June 2010. The present paper covers decision‐making and non‐surgical treatment. In particular, it will provide some background information on this part of the European core curriculum. The dentist, on graduation, must be competent at applying the principles of prevention of dental hard tissue disease processes (primary prevention) and progression when it has manifested itself (secondary prevention). The competences should apply in differing ways to patients of all ages. Goals of prevention should be clearly defined in order for outcomes to be evaluated, and a dentist should be competent at determining these outcomes. Although this concept is recognised by many academics and experts, clinical teaching, practice and health insurance coverage frequently emphasise surgical treatment. There are many reasons and obstacles that might account for this, and this paper suggests some reasons why this might be and makes suggestions for how these can be addressed in the future. One factor that is essential in the provision of a preventive, non‐surgical approach is that of communication with the patient. However, this unfortunately takes less space in the dental curricula compared with technical skills aimed at restorative procedures; this weighting needs to be more equally balanced.
Species distribution modelling as a macroecological tool: a case study using New World amphibians
Authors: Vasconcelos Tiago S. , Rodríguez Miguel Á , Hawkins Bradford A.
Published: October 2011

Although species distribution modelling (SDM) is widely accepted among the scientific community and is increasingly used in ecology, conservation biology and biogeography, methodological limitations generate potential problems for its application in macroecology. Using amphibian species richness in North and South America, we compare species richness patterns derived from SDM maps and ‘expert’ maps to evaluate if: 1) richness patterns derived from SDM are biased toward climate‐based explanations for diversity when compared to expert maps, since SDM methods are typically based on climatic variables; and 2) SDM is a reliable tool for generating richness maps in hyperrich regions where point occurrence data are limited for many species. We found that although three widely used SDM methods overestimated amphibian species richness in grid cells when compared to expert richness maps in both North and South America due to systematic overestimation of range sizes, diversity gradients were reasonably robust at broad scales. Further, climatic variables statistically explained patterns of richness at similar levels among the different richness sources, although climatic relationships were stronger in the much better known North America than in South America. We conclude that in the face of the high deforestation rates coupled with incomplete data on species distributions, especially in the tropics, SDM represents a useful macroecological tool for investigating broad‐scale richness patterns and the dynamics between species richness and climate.
Degree of mucositis and duration of neutropenia are the major risk factors for early post‐transplant febrile neutropenia and severe bacterial infections after reduced‐intensity conditioning
Authors: Facchini Luca , Martino Rodrigo , Ferrari Angela , Piñana José L. , Valcárcel David , Barba Pere , Granell Miguel , Delgado Julio , Briones Javier , Sureda Anna , Brunet Salut , Sierra Jorge
Published: October 2011

Background and objectives: Whether the intensity of the conditioning regimen affects febrile neutropenia (FN) and severe bacterial infections (SBIs) is not well established. We analyzed the risk factors (RFs) for the development of FN and SBI in the first 100 d post‐transplant in 195 consecutive adult recipients of a reduced‐intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC‐allo). Materials and methods: The RIC regimens consisted of fludarabine plus melphalan (62%) or busulphan (38%) (FluMel or FluBu). SBIs include pneumonia, urinary tract infections, and bacteremia. Results: FN occurred in 141 patients (72%), always in the first 30 d post‐allo‐RIC. However, a SBI occurred in only 27 patients (14%) during this early post‐transplant period (<day +30), while 29 evaluable patients (15%) developed a SBI in the intermediate post‐transplant period (days +31 to +100). In multivariate analysis, RFs for the development of FN included onset of neutropenia before day +5 after allo‐RIC (P < 0.02) and NCI CTC grade III–IV mucosal damage in the first 10 d post‐transplantation (P = 0.03). RFs identified to SBI by multivariate analysis included corticosteroid therapy before day +100 (P < 0.01), mycophenolate mofetil‐based graft‐versus‐host disease (GVHD) prophylaxis (P < 0.01), and previous SBI before day +30 (P < 0.01). The rate of SBI from day +30 to +100 varied according to the number of RFs; thus, the rate of SBI was 1% in patients without any RF, 17% in patients with one RF, 29% with one RFs, and 53% in those with all three RFs. Conclusions: After an RIC‐allo, FN and early SBI occurred mostly in patients with severe mucositis and early‐onset neutropenia, while postengraftment high‐dose steroid therapy for acute GVHD was the major RF.
The cellular and molecular mechanisms for neutropenia in Barth syndrome
Authors: Makaryan Vahagn , Kulik Willem , Vaz Frederic M. , Allen Christopher , Dror Yigal , Dale David C. , Aprikyan Andrew A.
Published: October 2011

Barth syndrome (BTHS), a rare, X‐linked, recessive disease, is characterized by neutropenia and cardiomyopathy. BTHS is caused by loss‐of‐function mutations of the tafazzin (TAZ) gene. We developed a model of BTHS by transfecting human HL60 myeloid progenitor cells with TAZ‐specific shRNAs. Results demonstrate a significant downregulation in TAZ expression, mimicking the effects of naturally occurring truncation mutations in TAZ. Flow cytometry analyses of cells with TAZ‐specific, but not scrambled, shRNAs demonstrate nearly twofold increase in the proportion of annexin V‐positive cells and significantly increased dissipation of mitochondrial membrane potential as determined by DIOC6 staining. Transfection of TAZ‐specific shRNA had similar effects in U937 myeloid cells but not in lymphoid cell lines. Further studies in HL60 myeloid progenitor cells revealed aberrant release of cytochrome c from mitochondria and significantly elevated levels of activated caspase‐3 in response to TAZ knockdown. Treatment with caspase‐specific inhibitor zVAD‐fmk resulted in substantially reduced apoptosis to near‐normal levels. These data suggest that neutropenia in BTHS is attributable to increased dissipation of mitochondrial membrane potential, aberrant release of cytochrome c, activation of caspase‐3, and accelerated apoptosis of myeloid progenitor cells, and that this defect can be partially restored in vitro by treatment with caspase‐specific inhibitors.