bluuebunny/crossref_metadata_2025 huggingface dataset:
Childhood growth of females with Kallmann syndrome and FGFR1 mutations
Authors: Hero Matti , Laitinen Eeva‐Maria , Varimo Tero , Vaaralahti Kirsi , Tommiska Johanna , Raivio Taneli
Published: May 2014

Objective

In search of phenotypic cues that would allow early detection of Kallmann syndrome (KS), we evaluated the paediatric phenotypes in a series of females with KS.

Design, Patients and Measurements

In this retrospective cohort study, we investigated childhood growth in six females with KS due to mutations in FGFR1 and evaluated their reproductive phenotypes later in life.

Results

While growth during early infancy and childhood was within normal limits, a decreasing trend in height SDS already from mid‐childhood occurred in most patients. The lowest height SDS (mean, −1·2 SDS) occurred between 14 and 15 years of age, before the start of hormone replacement therapy. As adults, these women required assisted reproductive techniques for fertility. One of the probands passed on her G48S mutation to her son, who showed normal reproductive hormone levels during the minipuberty of infancy.

Conclusions

Early diagnosis of female KS remains a challenge as early phenotypic signs, apart from anosmia, are scarce. Females with KS exhibit a slight reduction in growth rate during mid‐childhood, but normal growth rate during the minipuberty of infancy, despite congenital lack of ovarian oestrogen. Women harbouring FGFR1 mutations will have 50% chance of passing on the gene defect to their offspring. We recommend genetic counselling to all females with KS to be carried out as a part of family planning.
Treatment Options to Reduce Disease Activity After Natalizumab: Paradoxical Effects of Corticosteroids
Authors: Rossi Silvia , Motta Caterina , Studer Valeria , Boffa Laura , De Chiara Valentina , Castelli Maura , Barbieri Francesca , Buttari Fabio , Monteleone Fabrizia , Germani Giorgio , Macchiarulo Giulia , Weiss Sagit , Centonze Diego
Published: May 2014

Aim

Natalizumab (NTZ) discontinuation leads to multiple sclerosis (MS) recurrence, but represents the only known strategy to limit the risk of progressive multifocal leukoencephalopathy (PML) in JCV seropositive patients. Here, we compared the clinical and imaging features of three groups of patients who discontinued NTZ treatment.

Methods

We treated 25 patients with subcutaneous INFβ‐1b (INF group), 40 patients with glatiramer acetate (GA group), and 40 patients with GA plus pulse steroid (GA+CS group).

Results

Six of 25 patients (24%) of the INF group were relapse‐free 6 months after NTZ suspension. In GA group, a significant higher proportion of patients (26 of 40 patients, 65%) were relapse‐free (P < 0.05). Far from improving the clinical effects of GA in post‐NTZ setting, combination of GA+CS was associated with lower relapse‐free rate than GA alone (40% vs. 65%, P = 0.04). Also on MRI parameters, combination of GA+CS was associated with worse outcome than GA alone, as 22 of 26 subjects (84.6%) had MRI evidence of disease activity 6 months after NTZ discontinuation.

Conclusion

Corticosteroids should not be used in combination with GA to prevent post‐NTZ disease recurrence.
STATE INCOME TAXES AND MILITARY SERVICE MEMBERS' LEGAL RESIDENCY CHOICES
Authors: Afonso Whitney B.
Published: May 2014

Using military residency data from 1998 to 2005 across all 50 states, I find that income taxes deter legal residencies and that the effect grows as income increases. My results indicate that states with no income tax or with exemptions for military wages experience 100% and 39% more service member residencies, respectively, than states with an income tax. The influence of state tax policy increases with higher pay and tenure. My findings are in keeping with economic theory, which suggests that high income workers will migrate out of high tax areas and be replaced by low income workers. (JEL H24, H71, J61)
Research Participant‐Centered Outcomes at NIH‐Supported Clinical Research Centers
Authors: Kost Rhonda G. , Lee Laura N. , Yessis Jennifer L. , Wesley Robert , Alfano Sandra , Alexander Steven R. , Kassis Sylvia Baedorf , Cola Philip , Dozier Ann , Ford Dan E. , Harris Paul A. , Kim Emmelyn , Lee Simon Craddock , O'Riordan Gerri , Roth Mary‐Tara , Schuff Kathryn , Wasser June , Henderson David K. , Coller Barry S.
Published: May 2014

Background

Although research participation is essential for clinical investigation, few quantitative outcome measures exist to assess participants’ experiences. To address this, we developed and deployed a survey at 15 NIH‐supported clinical research centers to assess participant‐centered outcomes; we report responses from 4,961 participants.

Methods

Survey questions addressed core aspects of the research participants’ experience, including their overall rating, motivation, trust, and informed consent. We describe participant characteristics, responses to individual questions, and correlations among responses.

Results

Respondents broadly represented the research population in sex, race, and ethnicity. Seventy‐three percent awarded top ratings to their overall research experience and 94% reported no pressure to enroll. Top ratings correlated with feeling treated with respect, listened to, and having access to the research team (R2 = 0.80–0.96). White participants trusted researchers more (88%) than did nonwhite participants collectively (80%; p < 0.0001). Many participants felt fully prepared by the informed consent process (67%) and wanted to receive research results (72%).

Conclusions

Our survey demonstrates that a majority of participants at NIH‐supported clinical research centers rate their research experience very positively and that participant‐centered outcome measures identify actionable items for improvement of participant's experiences, research protections, and the conduct of clinical investigation.
Optimization of immunocytochemistry in cytology: comparison of two protocols for fixation and preservation on cytospin and smear preparations
Authors: Pinheiro C. , Roque R. , Adriano A. , Mendes P. , Praça M. , Reis I. , Pereira T. , Srebotnik Kirbis I. , André S.
Published: May 2014

Objective

A new protocol for fixation and slide preservation was evaluated in order to improve the quality of immunocytochemical reactions on cytology slides.

Methods

The quality of immunoreactions was evaluated retrospectively on 186 cytology slides (130 direct smears, 56 cytospins) prepared from different cytology samples. Ninety‐three of the slides were air dried, stored at −20 °C and fixed in acetone for 10 minutes (Protocol 1), whereas the other 93 were immediately fixed in methanol at −20 °C for at least 30 minutes, subsequently protected with polyethylene glycol (PEG) and stored at room temperature (Protocol 2). Immunocytochemical staining, with eight primary antibodies, was performed on a Ventana BenchMark Ultra instrument using an UltraView Universal DAB Detection Kit. The following parameters were evaluated for each immunoreaction: morphology preservation, intensity of specific staining, background and counterstain. The slides were blinded and independently scored by four observers with marks from 0 to 20.

Results

The quality of immunoreactions was better on methanol‐fixed slides protected with PEG than on air‐dried slides stored in the freezer:  = 14.44 ± 3.58 versus  = 11.02 ± 3.86, respectively (P < 0.001).

Conclusion

Immediate fixation of cytology slides in cold methanol with subsequent application of PEG is an easy and straightforward procedure that improves the quality of immunocytochemical reactions and allows the storage of the slides at room temperature.
Impact of inconclusive endoscopic ultrasound‐guided fine‐needle aspiration results in the management and outcome of patients with solid pancreatic masses
Authors: Sun Bo , Yang Xiujiang , Ping Bo , He Yiping , Zhang Zhaozhen
Published: May 2014

Background and Aim

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) can be inconclusive in diagnosing solid pancreatic masses. The aim of the present study was to evaluate the impact of an inconclusive EUS‐FNA in the management of patients with solid pancreatic masses.

Methods

This is a retrospective analysis of a prospective database of patients with solid pancreatic masses referred for EUS‐FNA between December 2011 and December 2013. Consecutive patients with inconclusive initial EUS‐FNA were included. Demographic, clinical, procedural and outcome data were analyzed.

Results

Over the study period, 387 patients underwent EUS‐FNA of solid pancreatic masses, of which 38 patients had inconclusive cytology. Of the 38 patients, 18 were categorized as atypical, two were categorized as indeterminate or suspicious for malignancy, and 18 were categorized as benign process. Subsequently, 24 (63.2%) patients achieved cytopathological diagnosis by repeat EUS‐FNA (8), transcutaneous FNA (4) and surgery (12). Repeat EUS‐FNA were done a median of 13 days after the index examination and resulted in conclusive diagnosis in 72.7% of cases. Five patients undergoing surgery were confirmed to have benign lesions. In 14 (36.8%) patients not receiving a positive cytopathological diagnosis, 11 were eventually confirmed to be malignant based on clinical outcome and imaging evidence.

Conclusions

Inconclusive EUS‐FNA could lead to unnecessary surgical procedures in patients with resectable solid pancreatic masses if no cytopathological diagnosis is obtained through either repeat or alternative diagnostic modalities. Repeat EUS‐FNA provided a conclusive diagnosis in a majority of cases, and therefore should be strongly considered ahead of other modalities.
Post‐natal assessment of gestational diabetes: fasting glucose or full glucose tolerance test?
Authors: Myers J. E. , Hasan X. , Maresh M. J. A.
Published: May 2014

Aims

To determine the performance of a fasting glucose sample compared with a full oral glucose tolerance test for the detection of glucose abnormalities in a diverse ethnic population after gestational diabetes.

Methods

Oral glucose tolerance test results for women attending post‐natal testing over a 10‐year (2003–2013) period at St Mary's Hospital, Manchester, UK were reviewed. Demographic data were also extracted from the hospital maternity database.

Results

The average attendance for a post‐natal oral glucose tolerance test was approximately 45% over the study period. The prevalence of diabetes was 4.8% (30/629), with a higher rate in women of Asian ethnicity compared with other groups (6.6% vs. 3.5%). The sensitivity for a fasting plasma glucose of ≥ 6.1 mmol/l was 90% (95% CI 74.4–96.5%) for the detection of diabetes and 61% (49.1–71.5%) for the detection of diabetes and/or impaired glucose tolerance, with specificities of 91% (88.8–93.3%) and 93% (91.0–95.2%), respectively. The positive and negative likelihood ratios for diabetes and impaired glucose tolerance were 10.4 (7.8–13.8), 0.11 (0.03–0.32) and 9.2 (6.4–13.3), 0.42 (0.31–0.56), respectively. A fasting plasma glucose threshold of 5.6 mmol/l improved the sensitivity for impaired glucose tolerance (from 61% to 77%), but made no difference to the sensitivity for diabetes.

Conclusions

The current study has demonstrated that detection of diabetes after gestational diabetes, in an ethnically diverse population using a fasting plasma glucose only, was approximately 90%. Compliance with post‐natal screening might improve if women attended for a fasting plasma glucose only; this strategy would identify approximately 90% of cases of diabetes and 40% of cases of impaired glucose tolerance.
Subcutaneous injection of hyaluronidase with recombinant human insulin compared with insulin lispro in type 1 diabetes
Authors: Garg S. K. , Buse J. B. , Skyler J. S. , Vaughn D. E. , Muchmore D. B.
Published: May 2014

Aims

Prandial treatment with human regular insulin for diabetes may result in early postprandial hyperglycaemia and late hypoglycaemia due to its slow onset and long duration of action. This study compared injections of recombinant human insulin (rHI) formulated with recombinant human hyaluronidase [rHuPH20] (INSULIN‐PH20) to insulin lispro for prandial treatment in subjects with type 1 diabetes (T1D).

Methods

After a 1‐month run‐in period using twice‐daily insulin glargine (or usual basal insulin therapy for pump users) with prandial lispro, 46 subjects with T1D (42 ± 13 years; body mass index: 26 ± 4 kg/m2; A1c: 6.8 ± 0.5%) were assigned to INSULIN‐PH20 or lispro in a random sequence for two consecutive, 12‐week periods as the prandial insulin in an intensive treatment regimen.

Results

The mean glycaemic excursion for INSULIN‐PH20 (0.96 ± 2.00 mmol/l) was comparable (p = 0.322) to lispro (0.80 ± 1.95 mmol/l). The 8‐point self‐monitored blood glucose profiles were also comparable in the two groups. Good glycaemic control (A1c) was maintained for both treatments at 12 weeks (INSULIN‐PH20: 7.0 ± 0.5%; lispro: 6.9 ± 0.6%). Overall rates of hypoglycaemia (≤3.9 mmol/l) were 24 events per patient per 4 weeks for INSULIN‐PH20 and 22 events for lispro. There were no significant differences in adverse events or immunogenicity between treatments and both treatments were well tolerated.

Conclusions

Unlike commercially available formulations of regular human insulin, a formulation of rHI with rHuPH20 was comparable to lispro for postprandial glucose excursions in a basal‐bolus treatment regimen for T1D patients. Glycaemic control, safety and tolerability profiles were comparable for both treatments.
Modulation of IL‐33/ST2 system in postinfarction heart failure: correlation with cardiac remodelling markers
Authors: Sánchez‐Más Jesús , Lax Antonio , Asensio‐López María del Carmen , Fernandez‐Del Palacio Maria J. , Caballero Luis , Santarelli Giorgia , Januzzi James L. , Pascual‐Figal Domingo A.
Published: May 2014

Background

Interleukin (IL)‐33 and sST2 are molecules with an opposite pathophysiologic implications in the myocardial response after acute myocardial infarction (AMI). Both may be a target for therapeutic interventions. The kinetics of IL‐33 and sST2 expression in infarcted myocardium and their correlation with the ongoing processes of fibrosis, inflammation and apoptosis remains poorly defined.

Materials and methods

Fifty Wistar rats underwent left anterior descending coronary artery surgical ligation and were sacrificed at 1, 2, 4, 12 or 24 weeks post‐AMI. A sham‐operated group was also included. The mRNA cardiac expression levels of IL‐33, sST2, fibrosis markers, inflammatory markers and apoptosis markers were assessed by RT‐PCR. The protein expression of IL‐33 was also measured by Western blotting.

Results

The mRNA levels of IL‐33 and sST2 were upregulated in the infarcted myocardium during the first week after AMI. However, while IL‐33 levels remained elevated during the first 12 weeks post‐AMI, sST2 levels showed a marked drop at 4 weeks. IL‐33 protein expression showed a similar kinetic than mRNA expression. The expression of sST2 positively correlated with cardiac gene expression of inflammatory and fibrosis markers. However, the IL‐33 level did not correlate with these cardiac remodelling markers. No correlation of sST2 with apoptosis markers was observed.

Conclusion

After AMI, expression of sST2 is rapidly upregulated during the first 4 weeks and, in contrast to IL‐33, its levels correlated with the ongoing processes of fibrosis and inflammation. These findings suggest differential regulation of IL33 and sST2. Therapeutic modulation of early sST2 expression may be of greater importance to prevent adverse remodelling after AMI.
Serum and urinary NGAL but not KIM‐1 raises in human postrenal AKI
Authors: Urbschat Anja , Gauer Stefan , Paulus Patrick , Reissig Manuel , Weipert Christine , Ramos‐Lopez Elizabeth , Hofmann Rainer , Hadji Peyman , Geiger Helmut , Obermüller Nicholas
Published: May 2014

Background

We examined the value of the novel acute kidney injury (AKI) markers neutrophil gelatinase‐associated lipocalin (NGAL) and kidney injury molecule‐1 (KIM‐1) in acute postrenal impairment. These biomarkers have been evaluated in prerenal and intrarenal AKI so far, but not in human acute postrenal kidney injury. With regard to multimorbid and critically ill patients the discrimination of different AKI origins often remains a challenge. As the trend goes towards a diagnostic panel of AKI markers, we hereby aim to contribute to evaluate further options of discrimination in an observational case‐control study.

Materials and methods

Blood and urine samples were obtained from 53 patients with acute obstructive nephropathy secondary to ureteral calculi and 52 age‐matched healthy controls. Serum NGAL (sNGAL), urinary NGAL (uNGAL) and urinary KIM‐1 (uKIM‐1) levels were determined using a commercially available ELISA kit, creatinine applying the Jaffé's method.

Results

While urinary levels of KIM‐1 were not significantly different between patients with obstructive nephropathy and controls, a striking increase in sNGAL (P < 0·001) and uNGAL (P < 0·01) levels was detected in the obstructive nephropathy group. Within the obstructive nephropathy group, sNGAL (P = 0·01) and uNGAL (P = 0·049) but not uKIM‐1 correlated positively with the white blood cell count and uNGAL correlated positively (P = 0·002) with the extent of leucocyturia.

Conclusions

High levels of sNGAL and uNGAL observed in stone‐induced acute obstructive nephropathy may represent a valuable marker of postrenal AKI. Low uKIM‐1 levels may help to discriminate postrenal AKI events using a panel of markers in this setting.
QUASI‐EXPERIMENTAL ANALYSIS ON THE EFFECTS OF ADOPTION OF A VALUE ADDED TAX
Authors: UFIER ALEX
Published: May 2014

Value added taxes (VATs) have become an important source of government funding in past decades, but little empirical work has been carried out on their macroeconomic impacts. As the decision to implement aVATis endogenous, regression methods analyzing the impact of the policy choice will yield biased estimates. To solve this problem, I first model theVATadoption decision for 192 countries using survival analysis. I then match adopters to non‐adopters using propensity score matching. I find thatVATadoption is associated with an increase in growth and investment as well as lower inflation and government spending as a share ofGDP. (JELH20, H21)
Surgical endodontics: past, present, and future
Authors: Gutmann James L.
Published: May 2014

“… every age should profit by the experience of the preceding ones; but without a record of what has been accomplished each investigator (or clinician) commences a new series of trials (or treatment modalities), and wanders over the same ground in search of truths (or outcomes) which have long been discovered; or adopt theories (or practices) that have been long ago discarded.”* (Note: present author's inserts in italics)  *Patrick JJR. The first period in the history of dentistry. Dent Rev 1889: 3: 426–437.
Endodontic pain
Authors: Rosenberg Paul A.
Published: May 2014

Fear of the pain associated with endodontic treatment remains a formidable hurdle for patients and dentists. Our culture and the media reinforce the belief that endodontics means pain. The result can be a patient's refusal to have endodontic treatment and opt instead for an extraction. In 2002, when the article “Clinical Strategies for Managing Endodontic Pain” was published in Endodontic Topics, the focus was on the diagnosis of pain, clinical procedures directed at the relief of pain, and the role of anxiety. Since then, it has become clear that other factors may predispose some patients to pain. Clinicians have had the experience of providing endodontic treatment for two patients of the same age and sex with similar teeth. Despite using an identical clinical approach, the patients' responses are remarkably different. While one does not require postoperative analgesics, the other has severe pain/swelling requiring an emergency visit. Although iatrogenic factors are always a possibility, there is increasing evidence that a patient's genetic make‐up, sex, and level of anxiety may affect their response to treatment. Patients' responses to an analgesic may also vary and these too may be linked to genetic variations or issues associated with a patient's sex or level of anxiety. This article reviews recent evidence in those areas as well as the use of cone beam computed tomography (CBCT) and its impact on diagnosis. Differentiation of odontogenic and non‐odontogenic pain is also discussed. Therapeutics has undergone significant change. Current clinical research concerning the combined use of ibuprofen/acetaminophen is reviewed.
The role of implant dentistry in the specialty of endodontics
Authors: Silvestrin Tory
Published: May 2014

The routine incorporation of the placement of endosseous dental implants into the armamentaria of endodontists is currently limited, but it is on the rise. A need exists for endodontists to address the increased patient interest in implant‐supported restorations. This can be accomplished concomitantly with educating patients about the predictability of various treatment options. Based on the experience that endodontists have in the diagnosis of complex endodontic problems, treating teeth with multiple clinical problems such as resorption, infractions, vertical root fractures, and evaluating the outcomes of various treatment procedures, they are uniquely qualified to discuss objectively with patients the risks and benefits related to treatment options that include endodontics and replacement with dental implants. By incorporating implant dentistry in the endodontic clinical practice, or at least becoming highly knowledgeable about the discipline of implant dentistry, the endodontist will be in a position to provide patients with valuable and practical information and services.
Enhanced bleaching treatment: opportunities for immune‐assisted melanocyte suicide in vitiligo
Authors: Webb Kirsten C. , Eby Jonathan M. , Hariharan Vidhya , Hernandez Claudia , Luiten Rosalie M. , Le Poole I. Caroline
Published: May 2014

Depigmentation in vitiligo occurs by progressive loss of melanocytes from the basal layer of the skin, and can be psychologically devastating to patients. T cell‐mediated autoimmunity explains the progressive nature of this disease. Rather than being confronted with periods of rapid depigmentation and bouts of repigmentation, patients with long‐standing, treatment‐resistant vitiligo can undergo depigmentation treatment. The objective is to remove residual pigmentation to achieve a cosmetically acceptable result – that of skin with a uniform appearance. In the United States, only the use of mono‐benzyl ether of hydroquinone (MBEH) is approved for this purpose. However, satisfactory results can take time to appear, and there is a risk of repigmentation. MBEH induces necrotic melanocyte death followed by a cytotoxic T‐cell response to remaining, distant melanocytes. As cytotoxic T‐cell responses are instrumental to depigmentation, we propose that combining MBEH with immune adjuvant therapies will accelerate immune‐mediated melanocyte destruction to achieve faster, more definitive depigmentation than with MBEH alone. As Toll‐like Receptor (TLR) agonists – imiquimod, CpG, and Heat Shock Protein 70 (HSP 70) – all support powerful Th1 responses, we propose that using MBEH in combination with these agents can achieve superior depigmentation results for vitiligo patients.
Is fisheries production within Large Marine Ecosystems determined by bottom‐up or top‐down forcing?
Authors: Mcowen Chris J , Cheung William W L , Rykaczewski Ryan R , Watson Reg A , Wood Louisa J
Published: May 2014

Understanding the mechanisms driving fisheries production is essential if we are to accurately predict changes under climate change and exploit fish stocks in a sustainable manner. Traditionally, studies have sought to distinguish between the two most prominent drivers, ‘bottom‐up’ (resource driven) and ‘top‐down’ (consumer driven); however, this dichotomy is increasingly proving to be artificial as the relative importance of each mechanism has been shown to vary through space and time. Nevertheless, the reason why one predominates over another within a region remains largely unknown. To address this gap in understanding, we identified the dominant driver of commercial landings within 47 ecosystems, encompassing a wide range of biogeochemical conditions and fishing practices to elucidate general patterns. We show that bottom‐up and top‐down effects vary consistently with past fishing pressure and oceanographic conditions; bottom‐up control predominates within productive, overfished regions and top‐down in relatively unproductive and under‐exploited areas. We attribute these findings to differences in the species composition and oceanographic properties of regions, together with variation in fishing practices and (indicative) management effectiveness. Collectively, our analyses suggest that despite the complexity of ecological systems, it is possible to elucidate a number of generalities. Such knowledge could be used to increase the parsimony of ecosystem models and to move a step forward in predicting how the global ocean, particularly fisheries productivity, will respond to climate change.
Does wet cupping on the interscapular region improve depression and anxiety?
Authors: Farahmand Seyed Kazem , Gang Li Zhi , Saghebi Seyed Ahmad , Mohammadi Maryam , Mohammadi Shabnam , Mohammadi Ghazaleh , Ferns Gordon A , Ghanbari Majid , Ghayour Razmgah Gholamreza , Ramazani Zahra , Ghayour‐Mobarhan Majid , Esmaily Habibollah , Azizi Hoda
Published: May 2014

Background

Metabolic syndrome is characterised by at least three of the following clinical features: abdominal obesity, dyslipidaemia, high blood pressure and glucose intolerance; it has also been associated with depression and anxiety. Cupping has been shown to benefit psychological well‐being by alleviating anger, hostility, depression and anxiety.

Objectives

To investigate the effects of wet cupping on depression and anxiety in patients with metabolic syndrome.

Methods

Altogether 136 patients with metabolic syndrome (aged 18–65 years) were included. Ten patients were excluded owing to a history of haemophilia, systemic disorder, infectious disease, stroke, heart attack, type 1 diabetes, secondary dyslipidaemia, renal dysfunction, epilepsy and drug therapy. Patients were randomly divided into an experimental group (n=63), which received dietary advice with wet cupping, and a control group (n=63) receiving dietary advice alone. Treatment was administered for 3 months. Depression and anxiety were assessed using the Beck Depression Inventory at 0, 6 and 12 weeks after treatment. Data were analysed using ANOVA.

Results

There were no statistically significant correlations between depression and anxiety and weight, BMI and lipid profile (P>0.05). However, there was a statistically significant association between the psychological parameters and blood pressure, age and gender (P<0.05). There was a significant variation in scores between assessment points of P<0.001 for both anxiety and depression, but these did not differ significantly between groups (P=0.78 and P=0.69, respectively).

Conclusion

Wet cupping on the interscapular region does not appear to be useful for the treatment of anxiety and depression in patients with metabolic syndrome.
Morphological and physiological traits for higher biomass production in perennial rhizomatous grasses grown on marginal land
Authors: Jones Michael B. , Finnan John , Hodkinson Trevor R.
Published: May 2014

A widespread criticism of growing energy crops is that they displace much needed food crops and cause upward pressure on food prices. One solution is the use of marginal land that is unfavourable for food production and is currently underutilized. However, the yield of crops growing on marginal land is reduced because they are subjected to a range of abiotic stresses such as extremes of temperature and rainfall and edaphic factors such as increased soil salinity. Therefore, to achieve acceptable economic returns on the use of this land it will be necessary to, on the one hand improve management practices and on the other to select for plant genotypes which are able to tolerate and potentially overcome the stressful conditions they are exposed to. Here, we review the morphological and physiological traits of perennial rhizomatous grasses that could be modified to overcome these stresses and to maximize biomass production on marginal land. The traits include aspects of crop phenology, canopy and leaf photosynthesis, biomass partitioning, nutrient and water use efficiency and heat, cold and salt tolerance. It is proposed that newly developed biotechnological methods combined with high‐throughput plant phenotyping offer opportunities to rapidly select new genotypes that could achieve economic yields on large areas of marginal land.
Deep Injection of Waste Water in the Western Canada Sedimentary Basin
Authors: Ferguson Grant
Published: May 2014

Injection of wastes into the deep subsurface has become a contentious issue, particularly in emerging regions of oil and gas production. Experience in other regions suggests that injection is an effective waste management practice and that widespread environmental damage is unlikely. Over the past several decades, 23 km3 of water has been injected into the Western Canada Sedimentary Basin (WCSB). The oil and gas industry has injected most of this water but large amounts of injection are associated with mining activities. The amount of water injected into this basin during the past century is 2 to 3 orders magnitude greater than natural recharge to deep formations in the WCSB. Despite this large‐scale disturbance to the hydrogeological system, there have been few documented cases of environmental problems related to injection wells. Deep injection of waste appears to be a low risk activity based on this experience but monitoring efforts are insufficient to make definitive statements. Serious uncharacterized legacy issues could be present. Initiating more comprehensive monitoring and research programs on the effects of injection in the WCSB could provide insight into the risks associated with injection in less developed sedimentary basins.
A Fuzzy Rule Based Remedial Priority Ranking System for Contaminated Sites
Authors: Polat Sener , Aksoy Aysegul , Unlu Kahraman
Published: May 2014

Contaminated site remediation is generally difficult, time consuming, and expensive. As a result ranking may aid in efficient allocation of resources. In order to rank the priorities of contaminated sites, input parameters relevant to contaminant fate and transport, and exposure assessment should be as accurate as possible. Yet, in most cases these parameters are vague or not precise. Most of the current remediation priority ranking methodologies overlook the vagueness in parameter values or do not go beyond assigning a contaminated site to a risk class. The main objective of this study is to develop an alternative remedial priority ranking system (RPRS) for contaminated sites in which vagueness in parameter values is considered. RPRS aims to evaluate potential human health risks due to contamination using sufficiently comprehensive and readily available parameters in describing the fate and transport of contaminants in air, soil, and groundwater. Vagueness in parameter values is considered by means of fuzzy set theory. A fuzzy expert system is proposed for the evaluation of contaminated sites and a software (ConSiteRPRS) is developed in Microsoft Office Excel 2007 platform. Rankings are employed for hypothetical and real sites. Results show that RPRS is successful in distinguishing between the higher and lower risk cases.
Factors Affecting Public‐Supply Well Vulnerability in Two Karst Aquifers
Authors: Musgrove MaryLynn , Katz Brian G. , Fahlquist Lynne S. , Crandall Christy A. , Lindgren Richard J.
Published: May 2014

Karst aquifers occur in a range of climatic and geologic settings. Nonetheless, they are commonly characterized by their vulnerability to water‐quality impairment. Two karst aquifers, the Edwards aquifer in south‐central Texas and the Upper Floridan aquifer in western Florida, were investigated to assess factors that control the movement of contaminants to public‐supply wells (PSWs). The geochemistry of samples from a selected PSW or wellfield in each aquifer was compared with that from nearby monitoring wells and regional PSWs. Geochemistry results were integrated with age tracers, flow modeling, and depth‐dependent data to refine aquifer conceptual models and to identify factors that affect contaminant movement to PSWs. The oxic Edwards aquifer is vertically well mixed at the selected PSW/wellfield, although regionally the aquifer is geochemically variable downdip. The mostly anoxic Upper Floridan aquifer is affected by denitrification and also is geochemically variable with depth. In spite of considerable differences in geology and hydrogeology, the two aquifers are similarly vulnerable to anthropogenic contamination. Vulnerability in studied PSWs in both aquifers is strongly influenced by rapid karst flowpaths and the dominance of young (<10 years) groundwater. Vulnerability was demonstrated by the frequent detection of similar constituents of concern in both aquifers (nitrate, atrazine, deethylatrazine, tetrachloroethene, and chloroform). Specific consideration of water‐quality protection efforts, well construction and placement, and aquifer response times to land‐use changes and contaminant loading are discussed, with implications for karst groundwater management.
The Effect of Modeled Recharge Distribution on Simulated Groundwater Availability and Capture
Authors: Tillman F.D , Pool D.R. , Leake S.A.
Published: May 2014

Simulating groundwater flow in basin‐fill aquifers of the semiarid southwestern United States commonly requires decisions about how to distribute aquifer recharge. Precipitation can recharge basin‐fill aquifers by direct infiltration and transport through faults and fractures in the high‐elevation areas, by flowing overland through high‐elevation areas to infiltrate at basin‐fill margins along mountain fronts, by flowing overland to infiltrate along ephemeral channels that often traverse basins in the area, or by some combination of these processes. The importance of accurately simulating recharge distributions is a current topic of discussion among hydrologists and water managers in the region, but no comparative study has been performed to analyze the effects of different recharge distributions on groundwater simulations. This study investigates the importance of the distribution of aquifer recharge in simulating regional groundwater flow in basin‐fill aquifers by calibrating a groundwater‐flow model to four different recharge distributions, all with the same total amount of recharge. Similarities are seen in results from steady‐state models for optimized hydraulic conductivity values, fit of simulated to observed hydraulic heads, and composite scaled sensitivities of conductivity parameter zones. Transient simulations with hypothetical storage properties and pumping rates produce similar capture rates and storage change results, but differences are noted in the rate of drawdown at some well locations owing to the differences in optimized hydraulic conductivity. Depending on whether the purpose of the groundwater model is to simulate changes in groundwater levels or changes in storage and capture, the distribution of aquifer recharge may or may not be of primary importance.
Therapeutic management and costs of severe haemophilia A patients with inhibitors in Italy
Authors: Abbonizio F. , Giampaolo A. , Coppola A. ,   the Italian Association of Haemophilia Centres (AICE), Arcieri R. , Hassan H. J.
Published: May 2014

Haemophilia A (HA) patients with high responding inhibitors require therapies with bypassing agents to control bleedings or Immune Tolerance Induction (ITI) to attempt inhibitor eradication and restore FVIII therapy. The aim of this study was to assess the therapeutic management and product consumption of HA inhibitor patients and the relative costs in Italy. A retrospective survey was performed utilizing data from the National Registry of Congenital Coagulopathies and from a specific questionnaire on product consumption of HA inhibitor patients over the year 2011. Among HA patients, 10% had currently detectable inhibitors; 24% of patients were undergoing ITI (mostly children) and 76% utilized bypassing agents. Patients on ITI consumed 45 000 000 IU of FVIII (median consumption/patient of 1 200 000 IU year−1). Patients receiving bypassing agents utilized 21 000 000 IU of aPCC (median consumption/patient of 360 000 IU year−1), and 38 000 mg of rFVIIa (median consumption/patient of 440 mg year−1). The annual cost/patient on ITI and on bypassing agents therapy was analysed. Recombinant products represen‐ted the product of choice for children therapies in >90% of the cases. FVIII prophylaxis of severe HA patients without inhibitor costs about half than therapy with bypassing agents and is three times less expensive than prophylaxis with such agents. Therefore, the possibility to restore FVIII prophylaxis, having eradicated the inhibitor through ITI, can justify the high costs of ITI treatment needed in the short term. Consistent with this notion, over the last years a 50% increase in the number of patients undergoing ITI in Italy was registered.
Effects of enoxaparin on myeloperoxidase release during hemodialysis
Authors: Gozdzikiewicz Joanna , Borawski Jacek , Koc‐Zorawska Ewa , Mysliwiec Michal
Published: May 2014

Myeloperoxidase (MPO) is a proteolytic and prooxidant enzyme largely assembled with the vascular wall, and a heparin‐binding protein. We studied if low‐molecular‐weight heparin enoxaparin administered for hemodialysis (HD) anticoagulation causes systemic MPO activation. Plasma MPO levels were measured in patients undergoing maintenance HD with an intravenous bolus of enoxaparin. Patients were retested during HD employing dialyzers with heparin‐grafted polyacrylonitrile membrane and no systemic enoxaparin administration. During enoxaparin‐anticoagulated HD plasma MPO levels strikingly increased in all patients (8.6‐fold at 10 minutes and 3.3‐fold at 120 minutes, both P < 0.0001). The increments were directly associated with the enoxaparin dosage and strongly inversely with the predialysis levels of the enzyme. The increase in plasma MPO during systemic heparin‐free HD was significantly less pronounced. Enoxaparin administered for HD anticoagulation induces a marked and dose‐dependent increase in plasma MPO as a plausibly favorable result of the liberation of the enzyme from the vascular wall.
Central vein perforation during tunneled dialysis catheter insertion: Principles of acute management
Authors: Pua Uei
Published: May 2014

Central venous perforation during dialysis catheter insertion is a potentially fatal complication. Prompt recognition and judicious initial steps are important in optimizing the outcome. The purpose of this manuscript is to illustrate the imaging features and steps in initial management.
Cellular metabolism modulation in T lymphocyte immunity
Authors: Liu Huanrong , Yang Hui , Chen Xi , Lu Yun , Zhang Zhengguo , Wang Jian , Zhang Ming , Xue Lixiang , Xue Feng , Liu Guangwei
Published: May 2014

T lymphocytes are a central component, and play an important role in controlling immunity and immunological diseases. Recent studies have shown that T cell metabolism is highly dynamic and has a tremendous impact on the modulation of T lymphocyte immunity. Specific metabolic pathways meet energy and biosynthetic requirements that can support specific T cell functional activities in immunity and immunological diseases. This review summarizes the recent progresses about the modulatory role of cell metabolism in T cell development, differentiation, activation and function in immunity. These might provide new opportunities to modulate the immune responses and treat clinical immunological diseases.

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Analysis of Statistical Interactions in Factorial Experiments
Authors: Kitsche A. , Schaarschmidt F.
Published: May 2014

Two or higher‐order factorial designs are very common in agricultural and horticultural experiments. The evaluation of such trials by analysis of variance (anova) and the corresponding F‐tests for the interaction effects covers only a global decision concerning the presence of interactions. This study presents a straightforward method, which provides a more detailed analysis of interactions via multiple contrast tests. The presented approach takes both the structure of each factor and the research question into account by building user‐defined product‐type contrasts. Simultaneous inference for these user‐specified interaction contrasts that controls the overall error rate is available. In addition to adjusted P‐values, it is recommended to use simultaneous confidence intervals to present the magnitude, direction and the biological relevance of the interaction effects. The proposed method is demonstrated using two horticultural trials. Furthermore, the authors provide a collection of worked examples using the R (A Language and Environment for Statistical Computing, 2013, R Foundation for Statistical Computing, Vienna, Austria) add‐on package statint stored on github (https://github.com/AKitsche/statint).
Commentary: Are ADHD symptoms habit‐like? – a commentary on Goodman et al (2014)
Authors: Tannock Rosemary
Published: May 2014

The recent publication of the latest version of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) unleashed a torrent of dissatisfaction with and criticism of the ongoing use of a symptom‐based classification system, based on descriptive phenotypical features. Thus, the ‘multiple memory systems’ framework proposed in the accompanying Annual Research Review by Goodman et al. (Journal of Child Psychology and Psychiatry, 55, 2014, XX) as a potential explanatory mechanism underlying several psychiatric disorders, is innovative and consistent with an emergent focus on transdiagnostic core mechanisms. In this commentary, I discuss the ‘merit and mire’ of the proposed framework, focusing on its potential for delineating neurobehavioral mechanisms underlying psychiatric disorders, with particular emphasis on one of the neurodevelopmental disorders, ADHD.
What weekday? How acute? An analysis of reported planned and unplanned GP visits by older multi‐morbid patients in the Patient Journey Record System database
Authors: Surate Solaligue David Emanuel , Hederman Lucy , Martin Carmel Mary
Published: May 2014

Rationale, aims and objectives

Timely access to general practitioner (GP) care is a recognized strategy to address avoidable hospitalization. Little is known about patients seeking planned (decided ahead) and unplanned (decided on day) GP visits. The Patient Journey Record System (PaJR) provides a biopsychosocial real‐time monitoring and support service to chronically ill and older people over 65 who may be at risk of an avoidable hospital admission. This study aims to describe reported profiles associated with planned and unplanned GP visits during the week in the PaJR database of regular outbound phone calls made by Care Guides to multi‐morbid older patients.

Methods

One hundred fifty consecutive patients with one or more chronic condition (including chronic obstructive pulmonary disease, heart/vascular disease, heart failure and/or diabetes), one or more hospital admission in previous year, and consecutively recruited from hospital discharge, out‐of‐hour care and GP practices comprised the study sample. Using a semistructured script, Care Guides telephoned the patients approximately every 3 week days, and entered call data into the PaJR database in 2011. The PaJR project identified and prompted unplanned visits according to its algorithms. Logistic regression modelling and descriptive statistics identified significant predictors of planned and unplanned visits and patterns of GP visits on weekdays reported in calls.

Results

In 5096 telephone calls, unplanned versus planned GP visits were predicted by change in health state, significant symptom concerns, poor self‐rated health, bodily pain and concerns about caregiver or intimates. Calls not reporting visits had significantly fewer of these features. Planned visits were associated with general and medication concerns, reduced social participation and feeling down. Planned visits were highest on Monday and trended downwards to Fridays. Unplanned visits were reported at the same rate each weekday and more frequently when the interval between calls was ≥3 days. The PaJR project Care Guides advised patients to make unplanned visits in 6.3% of calls and advised planned GP visits in 2.5% of calls.

Conclusion

Unplanned GP visits consistently indicated a significant change to worse health with planned visits presenting less acuity in this study of older multi‐morbid patients in general practice, when monitored by regular calls at about every 3 days. The PaJR study actively prompted GP visits according to its algorithms. Assessing and predicting acuity in older multi‐morbid patients appears to be a promising strategy to improve access to primary care, and thus to reducing avoidable hospital utilization. Further research is needed to investigate the topic on a wider scale.
Towards a programme theory for fidelity in the evaluation of complex interventions
Authors: Masterson‐Algar Patricia , Burton Christopher R. , Rycroft‐Malone Jo , Sackley Catherine M. , Walker Marion F.
Published: May 2014

Rationale, aims and objectives

This paper addresses the challenge of investigating fidelity in the implementation of a complex rehabilitation intervention designed to increase the level of independence in personal activities of daily living of stroke patients living in UK care homes. A programme theory of intervention fidelity was constructed to underpin a process evaluation running alongside a cluster randomized trial of the rehabilitation intervention.

Methods

The programme theory has been constructed drawing on principles of realist evaluation. Using data from in‐depth semi‐structured interviews (n = 17) with all occupational therapists (OTs) and critical incident reports from the trial (n = 20), and drawing from frameworks for implementation, the programme theory was developed.

Results

The programme theory incorporates four potential mechanisms through which fidelity within the trial can be investigated. These four programme theory areas are (1) the balancing of research and professional requirements that therapists performed in a number of areas while delivering the study interventions; (2) the OTs rapport building with care home staff; (3) the work focused on re‐engineering the personal environments of care home patients; and (4) the learning about the intervention within the context of the trial and its impacts over time.

Conclusions

These findings characterize the real‐world nature of fidelity within intervention research, and specifically the negotiated nature of implementation within clinical settings, including individual patients' needs. This research adds to the evidence base because current frameworks for fidelity neglect the importance of learning over time of individuals and across the time span of a trial.