bluuebunny/crossref_metadata_2025 huggingface dataset:
Marginal public health gain of screening for colorectal cancer: modelling study, based on WHO and national databases in the Nordic countries
Authors: Sigurdsson Johann A. , Getz Linn , Sjönell Göran , Vainiomäki Paula , Brodersen John
Published: April 2012

Aims  To estimate the potential gain of national screening programmes for colorectal cancer (CRC) by stool occult blood testing in the Nordic countries, with comparative reference to the burden of other causes of premature death.

Methods  Implementation of national screening programmes for CRC was modelled among people 55–74 years in accordance with the 2011 Cochrane review of biannual screening, using the faecal occult blood test (FOBT) for 10 years, resulting in 15% relative risk reduction in CRC deaths among all those invited [intention‐to‐treat; relative risk 0.85; confidence interval (CI) 0.78 to 0.92]. Our calculations are based on the World Health Organization and national databanks on death causes (ICD‐10) and the mid‐year number of inhabitants in the target group. For Finland, Denmark, Norway and Sweden, we used data for 2009. For Iceland, due to the population's small size, we calculated mean mortality for the period 2005–2009.

Results  Invitation to a CRC screening programme for 10 years could influence 0.5–0.9% (95%CI 0.4–1.2) of all deaths in the age group 65–74 years. Among the remaining 99% of premature deaths, around 50% were caused by lung cancer, other lung diseases, cardiovascular diseases and accidents, with some national variations.

Conclusions and implications  Establishment of a screening programme for CRC for people aged 55–74 can be expected to affect only a minor proportion of all premature deaths in the Nordic setting. From a public health perspective, prioritizing preventive strategies targeting more prevalent causes of premature death may be a superior approach.
Host‐jump drives rapid and recent ecological speciation of the emergent fungal pathogen Colletotrichum kahawae
Authors: SILVA DIOGO N. , TALHINHAS PEDRO , CAI LEI , MANUEL LUZOLO , GICHURU ELIJAH K. , LOUREIRO ANDREIA , VÁRZEA VÍTOR , PAULO OCTÁVIO S. , BATISTA DORA
Published: April 2012

Ecological speciation through host‐shift has been proposed as a major route for the appearance of novel fungal pathogens. The growing awareness of their negative impact on global economies and public health created an enormous interest in identifying the factors that are most likely to promote their emergence in nature. In this work, a combination of pathological, molecular and geographical data was used to investigate the recent emergence of the fungus Colletotrichum kahawae. C. kahawae emerged as a specialist pathogen causing coffee berry disease in Coffea arabica, owing to its unparalleled adaptation of infecting green coffee berries. Contrary to current hypotheses, our results suggest that a recent host‐jump underlay the speciation of C. kahawae from a generalist group of fungi seemingly harmless to coffee berries. We posit that immigrant inviability and a predominantly asexual behaviour could have been instrumental in driving speciation by creating pleiotropic interactions between local adaptation and reproductive patterns. Moreover, we estimate that C. kahawae began its diversification at <2200 bp leaving a very short time frame since the divergence from its sibling lineage (c. 5600 bp), during which a severe drop in C. kahawae’s effective population size occurred. This further supports a scenario of recent introduction and subsequent adaptation to C. arabica. Phylogeographical data revealed low levels of genetic polymorphism but provided the first geographically consistent population structure of C. kahawae, inferring the Angolan population as the most ancestral and the East African populations as the most recently derived. Altogether, these results highlight the significant role of host specialization and asexuality in the emergence of fungal pathogens through ecological speciation.
Nafamostat mesilate, a noncalcium compound, as an anticoagulant, induces calcium‐dependent haemolysis when infused with packed erythrocytes
Authors: Fujita H. , Sakuma R. , Fujimoto S. , Hazama Y. , Ohtake C. , Moriyama A. , Kuhara K. , Nishimura S.
Published: April 2012

Background: Nafamostat mesilate (NM), a protease inhibitor, is available for acute pancreatitis and disseminated intravascular coagulopathy and is used as an anticoagulant for haemodialysis in Japan. Co‐infusion of red cell concentrates (RCC) and intravenous drugs is usually contraindicated. Because of limited venous access, adherence to the guidelines may be compromised in some clinical settings. Therefore, we investigated the influence of co‐infusion of RCC and various anticoagulants on haemolysis in vitro.

Methods: We investigated the effect of co‐incubation of RCC and various anticoagulant drugs [NM, gabexate mesilate (GM), heparin] in packed erythrocytes. We evaluated haemolysis using lactate dehydrogenase and free haemoglobin. In addition, we also evaluated the influence of co‐incubation on phosphatidylserine (PS) expression on the erythrocyte membrane.

Results: GM and NM induced haemolysis in a dose‐dependent manner, which was inhibited by removal of citrate and pretreatment with the calcium chelator, ethylenediaminetetraacetic acid. In a dynamic experiment using an infusion pump, NM not only induced haemolysis during co‐infusion with RCC but also elevated PS expression dependent on extracellular calcium.

Conclusion: NM and GM induce haemolysis in packed erythrocytes in the presence of citrate that is dependent on extracellular calcium.
Direct volumetric flow cytometric quantitation of CD34+ stem and progenitor cells
Authors: Gutensohn K. , Nikolitsis A. , Gramatzki M. , Spitzer D. , Buwitt‐Beckmann U. , Humpe A.
Published: April 2012

Objectives: In this study, we compared a classic single‐platform (SP) method applying beads for enumeration of CD45+ or CD34+ cells with a new device allowing direct volumetric measurements of stem and progenitor cells.

Background: Following apheresis and cyropreservation, the precise enumeration of CD34+ cells as key parameter of graft quality is mandatory for the clinical course after transplantation. Currently, flow cytometry with SP technique represents the ‘gold standard’ for such determinations.

Methods/Materials: Fresh samples, 14 from mobilised peripheral blood (PB), 9 from apheresis products (AP) and 13 samples from frozen‐thawed (FT) haematopoietic progenitor cell grafts, were analysed for CD34+ cells, CD45+ cells, and in frozen‐thawed samples for viability by a bead‐based flow cytometric method and in parallel by a direct, volumetric flow cytometric method.

Results: Comparison of CD34+ analyses revealed a significant correlation (P < 0·01) for each material between both techniques with r = 0·95 (PB), r = 0·933 (AP) and r = 0·929 (FT). Also, for analysis of CD45+ cells µL−1, the measured numbers evaluated with the different techniques did not significantly differ for all three materials analysed. In frozen‐thawed samples, the analysis of viability was comparable for both techniques.

Conclusions: The results of this study demonstrate that a direct volumetric analysis of CD34+ cells µL−1 or CD45+ cells µL−1 is feasible. This technique represents a simple and economical approach for standardisation of progenitor and stem cell analyses.
Malnutrition in young children of rural Burkina Faso: comparison of survey data from 1999 with 2009
Authors: Beiersmann C. , Bountogo M. , Tiendrébeogo J. , Louis V. R. , Gabrysch S. , Yé M. , Jahn A. , Müller O.
Published: April 2012

Objective  For measurement of progress towards the Millennium Development Goal (MDG) 1, reliable data on nutrition indicators of specific countries are essential. Malnutrition is also the main determinant for childhood mortality, which is addressed in MDG 4.

Methods  In the health and demographic surveillance area of Kossi Province in north‐western Burkina Faso, nutritional parameters were compared in two cohorts of young children of the same age range from eight villages. Surveys took place in June and December of the year 1999 and 2009. A multivariate model was used to control for confounding variables.

Results  For the 1999 study, data were analysed for 179 and 197 children who took part in the June and December survey respectively. In 2009, corresponding data were analysed for 460 and 409 children. Prevalence of underweight was highest in December 1999 (42.6%) and lowest in December 2009 (34.1%). After adjustment for age, sex and village, there was a slight but not always significant improvement in the z‐scores of weight‐for‐age, weight‐for‐length, length‐for‐age, and mid‐arm circumference over time.

Conclusions  The findings from this study confirm the still unacceptable high prevalence of malnutrition in young children of rural sub‐Saharan Africa (SSA). Progress in the reduction of malnutrition remains slow on this continent making it rather unlikely that the corresponding MDGs will be achieved. Large‐scale multi‐sectoral community‐based interventions are urgently needed for a sustainable improvement of child health in SSA.
Susceptibility status of malaria vectors to insecticides commonly used for malaria control in Tanzania
Authors: Kabula Bilali , Tungu Patrick , Matowo Johnson , Kitau Jovin , Mweya Clement , Emidi Basiliana , Masue Denis , Sindato Calvin , Malima Robert , Minja Jubilate , Msangi Shandala , Njau Ritha , Mosha Franklin , Magesa Stephen , Kisinza William
Published: April 2012

Objective  The aim of the study was to monitor the insecticide susceptibility status of malaria vectors in 12 sentinel districts of Tanzania.

Methods  WHO standard methods were used to detect knock‐down and mortality in the wild female Anopheles mosquitoes collected in sentinel districts. The WHO diagnostic doses of 0.05% deltamethrin, 0.05% lambdacyhalothrin, 0.75% permethrin and 4% DDT were used.

Results  The major malaria vectors in Tanzania, Anopheles gambiae s.l., were susceptible (mortality rate of 98–100%) to permethrin, deltamethrin, lambdacyhalothrin and DDT in most of the surveyed sites. However, some sites recorded marginal susceptibility (mortality rate of 80–97%); Ilala showed resistance to DDT (mortality rate of 65% [95% CI, 54–74]), and Moshi showed resistance to lambdacyhalothrin (mortality rate of 73% [95% CI, 69–76]) and permethrin (mortality rate of 77% [95% CI, 73–80]).

Conclusions  The sustained susceptibility of malaria vectors to pyrethroid in Tanzania is encouraging for successful malaria control with Insecticide‐treated nets and IRS. However, the emergency of focal points with insecticide resistance is alarming. Continued monitoring is essential to ensure early containment of resistance, particularly in areas that recorded resistance or marginal susceptibility and those with heavy agricultural and public health use of insecticides.
Long‐term effects of malaria prevention with insecticide‐treated mosquito nets on morbidity and mortality in African children: randomised controlled trial
Authors: Louis Valérie R. , Bals Joëlle , Tiendrebéogo Justin , Bountogo Mamadou , Ramroth Heribert , De Allegri Manuela , Traoré Corneille , Beiersmann Claudia , Coulibaly Boubacar , Yé Maurice , Jahn Albrecht , Becher Heiko , Müller Olaf
Published: April 2012

Objective  The objective is to investigate the effect of malaria control with insecticide‐treated mosquito nets (ITNs) regarding possible higher mortality in children protected during early infancy, due to interference with immunity development, and to assess long‐term effects on malaria prevalence and morbidity.

Methods  Between 2000 and 2002, a birth cohort was enrolled in 41 villages of a malaria holoendemic area in north‐western Burkina Faso. All neonates (n = 3387) were individually randomised to ITN protection from birth (group A) vs. ITN protection from age 6 months (group B). Primary outcome was all‐cause mortality. In 2009, a survey took place in six sentinel villages, and in 2010, a census was conducted in all study villages.

Results  After a median follow‐up time of 8.3 years, 443/3387 (13.1%) children had migrated out of the area and 484/2944 (16.4%) had died, mostly at home. Long‐term compliance with ITN protection was good. There were no differences in mortality between study groups (248 deaths in group A, 236 deaths in group B; rate ratio 1.05, 95% CI: 0.889–1.237, P = 0.574). The survey conducted briefly after the rainy season in 2009 showed that more than 80% of study children carried asexual malaria parasites and up to 20% had clinical malaria.

Conclusion  Insecticide‐treated mosquito net protection in early infancy is not a risk factor for mortality. Individual ITN protection does not sufficiently reduce malaria prevalence in high‐transmission areas. Achieving universal ITN coverage remains a major challenge for malaria prevention in Africa.
Intubation of the morbidly obese patient: GlideScope® vs. Fastrach™
Authors: YDEMANN M. , ROVSING L. , LINDEKAER A. L. , OLSEN K. S.
Published: April 2012

Background

Several potential problems can arise from airway management in morbidly obese patients, including difficult mask ventilation and difficult intubation. We hypothesised that endotracheal intubation of morbidly obese patients would be more rapid using the GlideScope® (GS) (Verathon Inc Corporate Headquarters, Bothell, WA, USA) than with the Fastrach™ (FT) (The Laryngeal Mask Company Ltd, Le Rocher, Victoria, Mahe, Seychelles).

Methods

One hundred patients who were scheduled for bariatric surgery were randomised to tracheal intubation using either a GS or an FT. The inclusion criteria were age 18–60 years and a body mass index of ≥ 35 kg/m2. The primary end point was intubation time, and if intubation was not achieved after two attempts, the other method was used for the third attempt.

Results

The mean intubation time was 49 s using the GS and 61 s using the FT (P = 0.86). A total of 92% and 84% of the patients were intubated on the first attempt using the GS and the FT, respectively. One tracheal intubation failed on the second attempt when the GS was used, and five failed on the second attempt when the FT was used. There were no incidents of desaturation and no differences between the groups in terms of mucosal damage or intubation difficulty. We experienced one oesophageal intubation using GS and six oesophageal intubations in five patients using FT. There was no difference between the pain scores or incidence of post‐operative hoarseness associated with the two intubation techniques.

Conclusion

No significant difference between the two methods was found. The GS and the FT may therefore be considered to be equally good when intubating morbidly obese patients.
Tongue numbness following laryngeal mask airway Supreme™ and i‐gel™ insertion: two case reports
Authors: RUJIROJINDAKUL P. , PRECHAWAI C. , WATANAYOMNAPORN E.
Published: April 2012

We present two cases of transient lingual nerve injury that were associated with the use of a laryngeal mask airway Supreme™ (The Laryngeal Mask Company, Singapore) during lumbar discectomy in a 43‐year‐old female and i‐gel™ (Intersurgical, Berkshire, UK) during ovum pick up in a 33‐year‐old female. They presented with numbness at the tip of their tongues and spontaneously and fully recovered 2 weeks after their operations.
Lung elastance and transpulmonary pressure can be determined without using oesophageal pressure measurements
Authors: STENQVIST O. , GRIVANS C. , ANDERSSON B. , LUNDIN S.
Published: April 2012

Introduction

The aim of the present study was to demonstrate that lung elastance and transpulmonary pressure can be determined without using oesophageal pressure measurements.

Methods

Studies were performed on 13 anesthetized and sacrificed ex vivo pigs. Tracheal and oesophageal pressures were measured and changes in end‐expiratory lung volume (ΔEELV) determined by spirometry as the cumulative inspiratory‐expiratory tidal volume difference. Studies were performed with different end‐expiratory pressure steps [change in end‐expiratory airway pressure (ΔPEEP)], body positions and with abdominal load.

Results

A PEEP increase results in a multi‐breath build‐up of end‐expiratory lung volume. End‐expiratory oesophageal pressure did not increase further after the first expiration, constituting half of the change in ΔEELV following a PEEP increase, even though end‐expiratory volume continued to increase. This resulted in a successive left shift of the chest wall pressure–volume curve. Even at a PEEP of 12 cmH2O did the end‐expiratory oesophageal (pleural) pressure remain negative.

Conclusions

A PEEP increase resulted in a less than expected increase in end‐expiratory oesophageal pressure, indicating that the chest wall and abdomen gradually can accommodate changes in lung volume. The rib cage end‐expiratory spring‐out force stretches the diaphragm and prevents the lung from being compressed by abdominal pressure. The increase in transpulmonary pressure following a PEEP increase was closely related to the increase in PEEP, indicating that lung compliance can be calculated from the ratio of the change in end‐expiratory lung volume and the change in PEEP, ΔEELV/ΔPEEP.
Haemodynamic stability and pulmonary shunt during spontaneous breathing and mechanical ventilation in porcine lung collapse
Authors: VIMLÁTI L. , LARSSON A. , HEDENSTIERNA G. , LICHTWARCK‐ASCHOFF M.
Published: April 2012

Background

We investigated the haemodynamic stability of a novel porcine model of lung collapse induced by negative pressure application (NPA). A secondary aim was to study whether pulmonary shunt correlates with cardiac output (CO).

Methods

In 12 anaesthetized and relaxed supine piglets, lung collapse was induced by NPA (−50 kPa). Six animals resumed spontaneous breathing (SB) after 15 min; the other six animals were kept on mechanical ventilation (MV) at respiratory rate and tidal volume (VT) that corresponded to SB. All animals were followed for 135 min with blood gas analysis and detailed haemodynamic monitoring.

Results

Haemodynamics and gas exchange were stable in both groups during the experiment with arterial oxygen tension (PaO2)/inspired fraction of oxygen (FiO2) and pulmonary artery occlusion pressure being higher, venous admixture (Qva/Qt) and pulmonary perfusion pressure being lower in the SB group. CO was similar in both groups, showing slight decrease over time in the SB group. During MV, Qva/Qt increased with CO (slope: 4.3 %min/l; P < 0.001), but not so during SB (slope: 0.55 %min/l; P = 0.16).

Conclusions

This porcine lung collapse model is reasonably stable in terms of haemodynamics for at least 2 h irrespective of the mode of ventilation. SB achieves higher PaO2/FiO2 and lower Qva/Qt compared with MV. During SB, Qva/Qt seems to be less, if at all, affected by CO compared with MV.
Early removal of urinary catheter leads to greater post‐void residuals in patients with thoracic epidural
Authors: ZAOUTER C. , WUETHRICH P. , MICCOLI M. , CARLI F.
Published: April 2012

Background

A recent study showed that the removal of a bladder catheter is safe in presence of thoracic epidural analgesia (TEA). However, the ability to void satisfactorily can be affected. The aim of this investigation is to determine whether patients with TEA are able to recover the micturition process.

Methods

On the morning after the surgery patients were randomised into two groups: the early removal group (ERG) (n = 101), with the bladder catheter removed at the same time, and the standard group (SG) (n = 104), where the bladder catheter was kept as long as TEA was functioning (on average 3–5 days after surgery). Following the first micturition, patients underwent regular ultrasound scanning of the bladder until a post‐void residual (PVR) less than 200 ml was reached.

Results

All of the patients in the ERG and in the SG started to void and recovered satisfactorily their ability to void, reaching a PVR < 200 ml without requiring a transurethral catheterisation. However, the length of time to reach a PVR < 200 ml in the ERG was significantly longer compared with the SG (345 min ± 169 vs. 207 min ± 122, P < 0.0001).

Conclusion

In the presence of TEA, the removal of the bladder catheter on the morning after surgery leads to a transient impairment of the lower urinary tract function with no need for re‐catheterisation.
Frühe antimykotische Therapiestrategien: empirisch oder diagnostisch gesteuert?
Authors: Heinz Werner J. , Weissinger Florian
Published: April 2012

Eine frühe antimykotische Intervention kann helfen, invasive Mykosen erfolgreich zu therapieren.1 Für eine Gruppe von Patienten mit hohem Risiko für eine Pilzinfektion wurde in den letzten Jahren eine Aspergillus‐wirksame antimykotische Prophylaxe etabliert. Ebenso wurden die diagnostischen Möglichkeiten verbessert. Die Sensitivität des Galactomannan (GM)‐Tests wurde verbessert, und auch zum Nachweis von Glucan, einem Polysaccharid der Pilzzellwand, steht mittlerweile ein Testverfahren zur Verfügung. Dies kann helfen, frühe, diagnostisch gestützte Therapieansätze zu entwickeln. Die Aspergillus‐PCR, eine weitere sensitive Methode, wird nun international standardisiert und ob ihres sinnvollen Einsatzes geprüft. Weiterhin findet die Strategie der empirischen Therapie bei Fieber in Neutropenie häufig Anwendung, wenn kein Keimnachweis möglich ist. Sowohl diese empirische Strategie als auch die diagnostisch gestützte antimykotische Therapie tragen dazu bei, den Einsatz von Antimykotika gezielter zu steuern. Diese Strategien stellen Alternativen zu einer prophylaktischen, und damit sehr frühen und breiten Anwendung systemischer Antimykotika dar. Die Möglichkeiten und die aktuelle Studienlage zur empirischen und diagnostisch gesteuerten Therapie sollen im Folgenden dargestellt werden.
Minimum inhibitory concentrations of amphotericin B against Candida krusei isolates from a French teaching hospital laboratory: a retrospective study over 8 years
Authors: Murat Jean‐Benjamin , Lebeau Bernadette , Chumpitazi Bernabé , Cornet Muriel , Maubon Danièle , Faure Odile , Quesada Jean‐Louis , Thiebaut‐Bertrand Anne , Timsit Jean‐François , Pelloux Hervé
Published: April 2012

Recent studies have shown decreased susceptibility of Candida krusei to amphotericin B (AmB), in addition to its inherent resistance to fluconazole. The susceptibility of C. krusei to AmB was studied in the Parasitology–Mycology laboratory of Grenoble Teaching Hospital, France. Between 2003 and 2011, we analysed 200 C. krusei isolates from 130 patients. The isolates were mainly collected in intensive care, cardio‐thoracic and cancer/haematology units. Minimum inhibitory concentrations (MICs) were determined by the E‐test method. The modal MIC was 0.5 μg ml−1; the MIC50 and MIC90 (MICs encompassing 50% and 90% of all isolates tested, respectively) were 0.5 μg ml−1 and 1 μg ml−1. The Cuzick’s and Kendall’s tests showed a significant increase in MIC values between 2003 and 2011 (P = 0.001 and P ≤ 0.001, respectively), regardless of age or gender. No statistical difference was reached with these tests when the first 100 or 50 data were excluded. Despite the increase observed in the first period of the study, our results confirm the low AmB MICs reported in previous studies. However, some authors have recently reported much higher MICs. This discrepancy cannot be explained by method biases and could reflect C. krusei epidemiological differences among populations.
Muscle development and differentiation in the urodele Ambystoma mexicanum
Authors: Banfi Serena , Monti Laura , Acquati Francesco , Tettamanti Gianluca , de Eguileor Magda , Grimaldi Annalisa
Published: April 2012

Muscle differentiation has been widely described in zebrafish and
Xenopus, but nothing is known about this process in amphibian urodeles. Both anatomical features and locomotor activity in urodeles are known to show intermediate features between fish and anurans. Therefore, a better understanding of myogenesis in urodeles could be useful to clarify the evolutionary changes that led to the formation of skeletal muscle in the trunk of land vertebrates. We report here a detailed morphological and molecular investigation on several embryonic stages of
Ambystoma mexicanum and show that the first differentiating muscle fibers are the slow ones, originating from a myoblast population initially localized close to the notochord that forms a superficial layer on the somitic surface afterwards. Subsequently, fast fibers differentiation ensues. We also identified and cloned
A. mexicanum
Myf5 as a muscle‐specific transcriptional factor likely involved in urodele muscle differentiation.
Temporomandibular joint‐evoked responses by spinomedullary neurons and masseter muscle are enhanced after repeated psychophysical stress
Authors: Okamoto Keiichiro , Tashiro Akimasa , Chang Zheng , Thompson Randall , Bereiter David A.
Published: April 2012

Psychological stress is a risk factor for the development of musculoskeletal pain of the head and neck; however, the basis for this relationship remains uncertain. This study tested the hypothesis that psychophysical stress alone was sufficient to alter the encoding properties of spinomedullary dorsal horn neurons and masseter muscle activity in male rats. Repeated forced swim conditioning increased markedly both the background firing rate and temporomandibular joint (TMJ)‐evoked activity of neurons in deep dorsal horn, while neurons in superficial laminae were less affected. Stress also increased the responses to stimulation of facial skin overlying the TMJ of neurons in deep and superficial dorsal horn. TMJ‐evoked masseter muscle activity was enhanced significantly in stressed rats, an effect that was reduced by prior blockade of the spinomedullary junction region. These data indicated that repeated psychophysical stress induced widespread effects on the properties of medullary dorsal horn neurons and masseter muscle activity. The effects of stress were seen preferentially on neurons in deep dorsal horn and included enhanced responses to chemosensory input from the TMJ and mechanical input from overlying facial skin. The stress‐induced elevation in TMJ‐evoked masseter muscle activity matched well with the changes seen in dorsal horn neurons. It is concluded that the spinomedullary junction region plays a critical role in the integration of psychophysical stress and sensory information relevant for nociception involving deep craniofacial tissues.
Origin matters: widely distributed native and non‐native species benefit from different functional traits
Authors: Knapp Sonja , Kühn Ingolf
Published: April 2012

Recently, ecologists debated whether distinguishing native from non‐native species is sensible or not. One argument is that widespread and less widespread species are functionally different, whether or not they are native. An opposing statement points out ecologically relevant differences between native and non‐native species. We studied the functional traits that drive native and non‐native vascular plant species frequency in Germany by explaining species grid‐cell frequency using traits and their interaction with status. Native and non‐native species frequency was equally driven by life span, ploidy type and self‐compatibility. Non‐native species frequency rose with later flowering cessation date, whereas this relationship was absent for native species. Native and non‐native species differed in storage organs and in the number of environmental conditions they tolerate. We infer that environmental filters drive trait convergence of native and non‐native species, whereas competition drives trait divergence. Meanwhile, introduction pathways functionally bias the frequency of non‐native species.
Effect of topical anesthesia on evaluation of corneal sensitivity and intraocular pressure in rats and dogs
Authors: Kim Jury , Kim Nam‐Soo , Lee Ki‐Chang , Lee Hae‐Beom , Kim Min‐Su , Kim Hyung‐Seop
Published: April 2012

Objective  To determine the effect of 0.5% proparacaine in tonometry by evaluating corneal touch threshold (CTT) and intraocular pressure (IOP).

Animal studied  Nine rats (18 eyes, Sprague–Dawley) and 10 dogs (20 eyes, Beagle)

Procedures  The IOP and CTT were measured in each eye before and after topical anesthesia with 0.5% proparacaine. The IOP was evaluated using Tonopen for dogs and Tonolab for rats. The corneal sensitivity was evaluated by CTT through a Cochet–Bonnet aesthesiometer.

Results  The mean IOP was not significantly changed in rats or dogs before and after topical anesthesia. However, after application of proparacaine, CTT was significantly increased in both animal groups compared with that before application of proparacaine.

Conclusion  From this study, topical anesthesia was found to significantly lower the corneal sensitivity but have little effect on IOP measurements. In ophthalmologic examination, topical anesthesia can be used to reduce corneal sensation without an effect on IOP.
Retinal ganglion cell (RGC) death in glaucomatous beagles is not associated with mutations in p53 and NTF4 genes
Authors: Kato Kumiko , Sasaki Noboru , Shastry Barkur S.
Published: April 2012

Background  Glaucoma in humans is a second leading cause of irreversible vision loss in the world and can affect all age groups as well as all populations. The precise mechanism of retinal ganglion cell (RGC) death and progressive degeneration of optic nerve in glaucoma is not understood. It has been suggested that apoptosis is the common pathway that leads to the death of RGCs in glaucoma and that neurotrophin 4 (NTF4) protein plays a role in the protection of RGCs by activating tyrosine kinase receptors. Additionally, one previous study suggested that p53 codon 72 polymorphism (R72P) might have a greater susceptibility to apoptosis in some ethnic population. Glaucoma also occurs in dogs, and the primary glaucoma in beagles is inherited as an autosomal recessive trait. Although recently a candidate gene has been isolated, the mechanism underlying RGC death is not understood.

Method  To understand whether the same p53 and NTF4 pathway mechanism is involved in a beagle model of glaucoma, we have isolated NTF4 gene from dog and analyzed both p53 and NTF4 genes for mutations in glaucomatous animals.

Results  Our analyses failed to identify any disease‐causing mutations in both genes with the exception of two polymorphisms in NTF4 gene. However, these are not pathogenic changes because they are also present in normal animals and are not segregated with the disease.

Conclusion  These results suggest that impaired neurotrophin signaling or compromised trophic support to the retina and p53‐mediated apoptosis may not be the underlying mechanism of RGCs death in a beagle model of glaucoma.
Association of RASSF1A genotype and haplotype with the progression of clear cell renal cell carcinoma in Japanese patients
Authors: Kawai Yoshihisa , Sakano Shigeru , Okayama Naoko , Suehiro Yutaka , Matsuyama Hideyasu , Hinoda Yuji
Published: April 2012

What's known on the subject? and What does the study add?

Ras association domain family 1A (RASSF1A) is a tumour suppressor and regulates cell cycle, apoptosis and microtubule stability. This is the first study to identify associations between RASSF1A polymorphisms and clinicopathological parameters and survival in patients with clear cell renal cell carcinoma (CCRCC). RASSF1A genotyping may be useful for predicting the prognosis of the clinical course of CCRCC, and this finding might provide a better understanding of the mechanism underlying the development and progression of CCRCC. However, functional and prospective studies with a larger number of patients are needed to confirm the results.

OBJECTIVE

To compare Ras association domain family 1A (RASSF1A) genotypes or haplotypes with clinicopathological characteristics and survival rates of patients with clear cell renal cell carcinoma (CCRCC).

PATIENTS AND METHODS

The study cohort comprised 224 Japanese patients who underwent radical nephrectomy and had CCRCC confirmed by histopathological analysis.

Three common polymorphisms in the RASSF1A gene, 133Ala/Ser (G/T), ‐710C/T and ‐392C/T, were genotyped using TaqMan assays and haplotypes were analysed using appropriate software.

RESULTS

Patients with CCRCC with RASSF1A ‐710TT genotype exhibited a significantly higher tumour stage and higher stage grouping than those with ‐710CC or ‐710CT (P = 0.005 and P = 0.032, respectively).

There was no significant association between 133Ala/Ser or ‐392C/T genotype and clinicopathological characteristics.

RASSF1A 133Ala‐710T‐392T haplotype and ‐710TT genotype were significantly associated with poorer recurrence‐free survival rates (P = 0.038 and P = 0.007, respectively).

CONCLUSIONS

This is the first study to identify associations between RASSF1A polymorphisms and clinicopathological parameters and survival in patients with CCRCC.

RASSF1A genotyping may be useful in predicting the prognosis of the clinical course of CCRCC, and this finding might provide a better understanding of the mechanism underlying the development and progression of CCRCC.

Functional and prospective studies with a larger number of patients are needed to confirm the results.
Ability of C‐reactive protein to complement multiple prognostic classifiers in men with metastatic castration resistant prostate cancer receiving docetaxel‐based chemotherapy
Authors: Pond Gregory R. , Armstrong Andrew J. , Wood Brian A. , Leopold Lance , Galsky Matthew D. , Sonpavde Guru
Published: April 2012

Study Type – Retrospective analysis of clinical trial

Level of Evidence 3

What's known on the subject? and What does the study add?

Serum C‐reactive protein (C‐reactive protein) is emerging as a potential novel prognostic factor in metastatic castration‐resistant prostate cancer (mCRPC).

In the present study, a prospective trial was investigated retrospectively and a significant prognostic impact for C‐reactive protein that was independent of multiple published prognostic models was identified in men receiving docetaxel‐based chemotherapy for mCRPC. Prospective validation is warranted.

OBJECTIVE

Given the recent emergence of C‐reactive protein levels as a novel prognostic factor in men with metastatic castration‐resistant prostate cancer (mCRPC), we sought to evaluate the independent prognostic ability of C‐reactive protein in the context of published prognostic nomograms, risk grouping and disease state models in men receiving docetaxel‐based chemotherapy for mCRPC.

PATIENTS AND METHODS

A large randomized phase II trial (CS‐205) of mCRPC patients who received docetaxel‐prednisone + AT‐101 (Bcl‐2 inhibitor) or docetaxel‐prednisone + placebo was analyzed retrospectively (n= 220).

Overall survival (OS), progression‐free survival (PFS) and measures of discriminatory ability were assessed in a hypothesis‐generating analysis using Cox regression and concordance probabilities.

Patients from both treatment groups were combined for this analysis because no significant differences in outcomes were observed.

Because some factors used in nomograms were not collected or defined differently, risk was estimated based on slightly modified versions of nomograms.

RESULTS

C‐reactive protein was independently prognostic for OS and PFS (P≤ 0.002) after adjusting for all modeled risk estimates and classifiers.

C‐reactive protein showed a concordance probability of 0.65 for both OS and PFS.

A 10‐factor modified prognostic model based on the TAX327 trial had the greatest observed discrimination ability for OS and PFS (concordance probability = 0.623 and 0.603, respectively) among the modified nomograms or classifiers.

Adding the TAX327 model risk estimates to C‐reactive protein did not substantially increase discrimination ability over C‐reactive protein alone.

CONCLUSIONS

Current prognostic classifications provide modest discrimination of outcomes in mCRPC receiving docetaxel‐based chemotherapy, highlighting the need for improved risk‐based models.

Baseline C‐reactive protein appears to be an useful, independent prognostic factor and prospective external validation is warranted.
Preoperative metastatic status, level of thrombus and body mass index predict overall survival in patients undergoing nephrectomy and inferior vena cava thrombectomy
Authors: Spiess Philippe E. , Kurian Tony , Lin Hui‐Yi , Rawal Bhupendra , Kim Tim , Sexton Wade J. , Pow‐Sang Julio M.
Published: April 2012

Study Type – Prognosis (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

Little is known about the prognostic impact of body mass index (BMI) and obesity on patients with locally advanced kidney cancer. Previous studies suggest that clinical/pathological stage, the proximal extent of the tumour thrombus, direct vascular wall invasion, and preoperative performance status may all constitute important prognostic factors within this patient population.

The present study shows that a patient's metastatic status, higher level of tumour thrombus, and lower BMI all constitute adverse predictors of overall survival in patients who have RCC with inferior vena cava tumour thrombus.

OBJECTIVE

To determine which clinical variables, including body mass index (BMI), predict overall survival (OS) after nephrectomy with inferior vena cava (IVC) thrombectomy for renal cell carcinoma (RCC) with tumour thrombus.

PATIENTS AND METHODS

After institutional review board approval, a retrospective analysis of all patients (N= 100) undergoing nephrectomy and IVC thrombectomy for RCC from 1989 to 2010 were reviewed. One patient was excluded owing to missing clinical information leaving 99 patients in the study cohort.

Patients were placed into one of two subgroups, based on their preoperative BMI (BMI ≤30 kg/m2 or BMI >30 kg/m2).

Complications, blood loss, level of tumour thrombus, side of tumour and follow‐up data were tabulated.

RESULTS

Fifty‐six patients had a BMI ≤30 kg/m2 and 43 patients had a BMI >30 kg/m2. Intraoperative complications occurred in 14% of those with BMI >30 kg/m2 and 5.4% of those with a BMI ≤30 kg/m2 (P= 0.171).

On multivariate analysis, a higher thrombus level (III/IV vs I/II) and the presence of metastatic disease at time of diagnosis was associated with a worse OS (P= 0.041 and P < 0.001, respectively).

The subgroup with a higher preoperative BMI had a significantly better OS (hazard ratio 0.42; 95% confidence interval 0.22–0.80, P= 0.009).

Similarly, our Kaplan–Meier survival analysis showed an improved OS in the patient cohort with a BMI >30 kg/m2 (P= 0.016).

CONCLUSION

Important predictors of outcome in patients undergoing nephrectomy with IVC thrombectomy for RCC with tumour thrombus include preoperative BMI, level of IVC tumour thrombus, and metastatic status at time of surgery.
Variables associated with corneal confocal microscopy parameters in healthy volunteers: implications for diabetic neuropathy screening
Authors: Wu T. , Ahmed A. , Bril V. , Orszag A. , Ng E. , Nwe P. , Perkins B. A.
Published: April 2012

Diabet. Med. 29, e297‐e303 (2012)

Aim  Corneal confocal microscopy is a promising screening method for diabetic neuropathy. Although much research in this field has been accomplished, we aimed to determine and confirm the known clinical and eyewear variables associated with the parameters of corneal confocal microscopy specifically in healthy volunteers, in particular associations with corneal nerve fibre length.

Methods  Clinical characteristics, electrophysiological examination and a general clinical eye history were collected from 64 healthy volunteers. Corneal confocal microscopy was performed to determine corneal nerve fibre length, corneal nerve branch density, corneal nerve fibre density and tortuosity coefficient. Univariate and multivariate linear regression analysis was used to determine clinical variables associated with corneal nerve fibre length parameters.

Results  We observed that corneal nerve fibre length has a broad distribution in healthy volunteers (18 ± 4 mm/mm2, 95% confidence interval, 12.3–25.7 mm/mm2). Multivariate regression analysis demonstrated that HbA1c was the only independent clinical factor to account for variations in corneal nerve fibre length, independent of age and status of contact lens wear.

Conclusions  This study does not provide convincing evidence that corneal nerve fibre length is independently associated with age or the wearing of contact lenses, and that these factors are therefore unlikely to hinder valid screening for polyneuropathies such as diabetic neuropathy. Furthermore, the strong inverse association of corneal nerve fibre length with glycaemic exposure may support the use of this parameter to detect subclinical pre‐diabetic nerve injury.
Good choices, great future: An applied theatre prevention program to reduce alcohol‐related risky behaviours during Schoolies
Authors: QUEK LAKE‐HUI , WHITE ANGELA , LOW CHRISTINE , BROWN JUDITH , DALTON NIGEL , DOW DEBBIE , CONNOR JASON P.
Published: April 2012

Introduction and Aims. The contextual and temporal factors of post‐school celebratory events (‘Schoolies’) place young people at elevated risk of excessive drinking compared with other social occasions. This study investigates the impact of an applied theatre prevention program ‘Choices’ in reducing the risk of drinking and other risk behaviours during Schoolies celebrations.

Design and Methods. Choices was delivered in the last term of Year 12 across 28 North Queensland schools. A total of 352 school leavers (43.1% male, mean age = 17.14 years) completed a questionnaire at Whitsunday Schoolies, Queensland, Australia on 23–24 November 2010. Nearly 49% of respondents had attended Choices. The survey included measures of alcohol use, illicit drug use and associated problems during Schoolies and a month prior to Schoolies.

Results. After controlling for gender and pre‐Schoolies drinking, school leavers who attended Choices were significantly less likely to report illicit drug use (OR = 0.51, P < 0.05) and problem behaviours (OR = 0.40, P < 0.01) than those who did not attend Choices. There was, however, no intervention effect in risky drinking (i.e. drank on 5 or more days, typical amount five or more standard drink and binge drank on 3 or more days) at Schoolies (OR = 0.92, P = 0.80).

Discussion and Conclusions. Delivery of a youth‐specific applied theatre prevention program employing a harm minimisation framework may be effective in reducing high‐risk behaviours associated with alcohol consumption at celebratory events, even if young people expect to engage in excessive alcohol consumption. [Quek L‐H, White A, Low C, Brown J, Dalton N, Dow D, Connor JP. Good choices, great future: An applied theatre prevention program to reduce alcohol‐related risky behaviours during Schoolies. Drug Alcohol Rev 2012;31:897–902]
EFFECTS OF WELFARE REFORM ON ILLICIT DRUG USE OF ADULT WOMEN
Authors: CORMAN HOPE , DAVE DHAVAL M. , DAS DHIMAN , REICHMAN NANCY E.
Published: April 2012

Exploiting changes in welfare policy across states and over time and comparing relevant population subgroups within an econometric difference‐in‐differences framework, we estimate the effects of welfare reform on adult women's illicit drug use from 1992 to 2002, the period during which welfare reform unfolded in the United States. The analyses are based on all available and appropriate national data sets, each offering unique strengths and measuring a different drug‐related outcome. We investigate self‐reported illicit drug use (from the National Household Surveys on Drug Abuse and National Surveys on Drug Use and Health), drug‐related prison admissions (from the National Corrections Reporting Program), drug‐related arrests (from Federal Bureau of Investigation Uniform Crime Reports), and drug‐related emergency department episodes (from the Drug Abuse Warning Network). We find robust evidence that welfare reform led to a 10%–21% decline in illicit drug use among women at risk of relying on welfare, as well as associated declines in drug‐related arrests (6%–7%), drug‐related hospital emergency department episodes (7%–11%), and possibly drug‐related prison admissions (11%–19%). The findings indicate that an appropriately designed welfare system with sufficient job opportunities for those who are able to work can result in both increases in employment and decreases in drug use. (JEL I38, K42, J21)
Production of non‐glycosylated recombinant proteins in Nicotiana benthamiana plants by co‐expressing bacterial PNGase F
Authors: Mamedov Tarlan , Ghosh Ananya , Jones R. Mark , Mett Vadim , Farrance Christine E. , Musiychuk Konstantin , Horsey April , Yusibov Vidadi
Published: April 2012

Application of tools of molecular biology and genomics is increasingly leading towards the development of recombinant protein‐based biologics. As such, it is leading to an increased diversity of targets that have important health applications and require more flexible approaches for expression because of complex post‐translational modifications. For example, Plasmodium parasites may have complex post‐translationally modified proteins such as Pfs48/45 that do not carry N‐linked glycans (Exp. Parasitol. 1998; 90, 165.) but contain potential N‐linked glycosylation sites that can be aberrantly glycosylated during expression in mammalian and plant systems. Therefore, it is important to develop strategies for producing non‐glycosylated forms of these targets to preserve biological activity and native conformation. In this study, we are describing in vivo deglycosylation of recombinant N‐glycosylated proteins as a result of their transient co‐expression with bacterial PNGase F (Peptide: N‐glycosidase F). In addition, we show that the recognition of an in vivo deglycosylated plant‐produced malaria vaccine candidate, Pfs48F1, by monoclonal antibodies I, III and V raised against various epitopes (I, III and V) of native Pfs48/45 of Plasmodium falciparum, was significantly stronger compared to that of the glycosylated form of plant‐produced Pfs48F1. To our knowledge, neither in vivo enzymatic protein deglycosylation has been previously achieved in any eukaryotic system, including plants, nor has bacterial PNGase F been expressed in the plant system. Thus, here, we report for the first time the expression in plants of an active bacterial enzyme PNGase F and the production of recombinant proteins of interest in a non‐glycosylated form.
Beyond the ‘At Risk’ Individual: Housing and the Eradication of Poverty to Prevent Homelessness
Authors: Parsell Cameron , Marston Greg
Published: April 2012

A prevention framework represents one of the fundamental means of the Australian Government's contemporary drive to achieve permanent reductions in homelessness. Consistent with prevailing policies in the UK and US, Australia has approached homelessness prevention through identification and early intervention of individuals ‘at risk’ of homelessness. In this article we suggest that prevention strategies focused on the risk factors that individual pose obscures efforts to address the underlying structural factors that contribute to homelessness, or to reduce the prevalence of homelessness at the overall population level. The article examines the efficacy of increasing the supply of affordable housing to prevent homelessness, but suggests that the provision of housing alone may be insufficient to realising related well‐being objectives. In turn, it is proposed that policy which focuses on poverty reduction has the capacity to achieve the sustainable prevention of homelessness ambitions.