bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of PCR-RFLP Analysis to Monitor Fungicide Resistance inCercospora beticolaPopulations from Sugarbeet (Beta vulgaris) in Michigan, United States
Authors: Rosenzweig N. , Hanson L. E. , Clark G. , Franc G. D. , Stump W. L. , Jiang Q. W. , Stewart J. , Kirk W. W.
Published: September 2014

Genetic resistance to Quinone outside inhibitor (QoI) and benzimidazole fungicides may be responsible for a recent decline in efficacy of chemical control management strategies for Cercospora leaf spot (CLS) caused by Cercospora beticola in Michigan sugarbeet (Beta vulgaris) fields. The target genes and fungicide resistance mutations are known for these two fungicides. Based on this, two standard polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assays were developed to detect the G143A and E198A point mutations in the fungal mitochondrial cytochrome b and the β-tubulin genes, respectively. These mutations confer a high level of resistance to either QoI or benzimidazole fungicides. The presence of the G143A and E198A mutations was monitored within C. beticola populations recovered from Michigan sugarbeet production fields collected in 2012. Both the QoI-resistant cytochrome b allele and the benzimidazole-resistant β-tubulin allele were detected directly from leaf tissue following a PCR-RFLP assay. Using either detection assay, the G143A and E198A mutations were detected in over 90% of the 118 field samples originating from Michigan sugarbeet production under fungicide management programs for CLS control. Monitoring of the G143A and E198A mutations in fields located in 9 counties and 58 townships indicated that the mutations were widespread in Michigan sugarbeet production areas. The PCR-based assays used and developed in this study were effective in detecting the presence of the G143A and E198A mutations in C. beticola field populations from Michigan.
First Report of Bursaphelenchus mucronatus kolymensis Associated with Pinus sylvestris in Serbia
Authors: Bačić J. , Stare B. G. , Urek G. , Širca S.
Published: September 2014

Bursaphelenchus mucronatus kolymensis (Korentchenko) Braasch et al. (1), also referred to as the European type of B. mucronatus, is morphologically very similar to the pine wood nematode (PWN) B. xylophilus (Steiner & Buhrer) Nickle, the causal agent of pine wilt disease. The main morphological difference between the two species is the shape of the female tail mucro (3); however, some populations of PWN vary in mucro shape, which can lead to misidentification. Since PWN was found and identified for the first time in Portugal in 1999 (4), concern about the spread of PWN to pines and other conifers all over Europe has increased. Therefore, the PWN survey in every European country is essential. In 2011, the Serbian Ministry of Agriculture, Forestry and Water Management implemented phytosanitary measures for detection of PWN in the territory of the Republic of Serbia. In September 2013, wood samples were collected from a 40-year-old wilted Pinus sylvestris located on Divcibare Mountain, western Serbia. Nematodes were extracted by a modified Baermann funnel method. Nematode specimens (10 females and 10 males) were characterized by an Aphelenchoid-type esophagus, female vulva flap, mucro on the end of female tail, and males with paired arcuate spicules. Morphological identification matched that of B. mucronatus kolymensis (1). The specific morphometric evidence for this European type subspecies of B. mucronatus was sub-cylindrical female tail with mucro 3 to 4 μm long, digitate, well offset from tail (5). Species identification was confirmed by PCR-RFLP of the rDNA ITS region using one female and one male nematode separately (2). The sizes of restricted DNA fragments as determined with agarose gel and capillary electrophoresis were in compliance with reported data in the literature (2,4) and support the identification of the nematode as B. mucronatus kolymensis. To our knowledge, this is the first report of any species belonging to Bursaphelenchus genus in Serbia. The presence of B. mucronatus kolymensis in Serbia indicates the possibility of establishment and spread of PWN. Therefore, the measures taken in case of PWN occurrence should be prepared and training foresters to identify pine wilt disease symptoms should be encouraged in Serbia.

References: (1) H. Braasch et al. J. Nematode Morphol. Syst. 14:77, 2011. (2) W. Burgermeister et al. Nematology 11:649, 2009. (3) Y. Mamiya and N. Enda. Nematologica 25:353, 1979. (4) M. M. Mota et al. Nematology 1:727, 1999. (5) M. M. Mota and P. Vieira. Page 146 in: Pine Wilt Disease: A Worldwide Threat to Forest Ecosystems. Springer Science and Business Media, 2008.
A Multiplex Real-Time PCR Assay for the Detection of Puccinia horiana and P. chrysanthemi on Chrysanthemum
Authors: Demers Jill E. , Crouch Jo Anne , Castlebury Lisa A.
Published: September 2014

Puccinia horiana, the cause of chrysanthemum white rust, is a regulated fungal plant pathogen in the United States, while P. chrysanthemi, the cause of chrysanthemum brown rust, is a widespread but less destructive pathogen. Accurate identification is essential to enforce quarantine measures, but the two species cannot be differentiated visually in the absence of mature spores or symptoms. A multiplex real-time PCR assay was developed to detect and discriminate between P. chrysanthemi and P. horiana. Species-specific hydrolysis probes labeled with different fluorescent dyes were designed based on the rDNA internal transcribed spacer region. Seven fresh samples and 270 herbarium specimens of chrysanthemum rust were tested with the assay with results confirmed using spore morphology. P. horiana and P. chrysanthemi were accurately detected from all fresh samples, and as little as 1 pg of template DNA was reproducibly detected. Of the herbarium specimens, 99% were positive for at least one species using the multiplex assay with 7% positive for both species. This multiplex assay can discriminate between P. chrysanthemi and P. horiana and provides an additional tool for identification of P. horiana to ensure appropriate application of quarantine measures.
First Report of Meloidogyne javanica Parasitizing Duboisia sp. in Paraná State, Brazil
Authors: Machado A. C. Z. , Dorigo O. F. , Boss A. , Tironi P.
Published: September 2014

Duboisia sp. is a small tree belonging to the family Solanaceae originating from the rainforest areas of the eastern coast of Australia. Dried leaves are used for the extraction of pharmaceutical alkaloids, making this a commercially viable crop. The root-knot nematode Meloidogyne incognita has been reported parasitizing Duboisia myoporoides (5); however, no information of other root-knot nematode species associated with this plant was found. Duboisia sp. is cultivated at Solana Farm, near Arapongas (23°25′08″ S, 51°25′26″ W), Paraná State, Brazil. During the renovation of a production field in this municipality, galled roots were observed on plants and samples were submitted to the Nematology Laboratory at Instituto Agronômico do Paraná, IAPAR, on December 2013. Plants did not exhibit any above-ground symptoms. The specimens were identified through perineal patterns and esterase phenotypes of 20 adult females extracted from dissected roots (2,3) and morphometrics of 10 second-stage juveniles extracted from roots using the blender-sieving method (1). Morphological characteristics were consistent with those described for M. javanica (4). Females had rounded perineal patterns with low, trapezoid shape dorsal arch, striae smooth interrupted by a pair of incisures on both sides, corresponding to lateral fields, clearly demarcated from striae by more or less parallel lines, tail whorl often distinct (4). The juvenile mean body length was 459.9 ± 28.7 μm and tail length averaged 51.6 ± 5.1 μm, with 10 to 16 μm long hyaline region and finely rounded tail tip (4). Results from the esterase electrophoresis were typical of M. javanica (2) with the J3 (Rm = 1.0, 1.3, and 1.4) phenotype being obtained. To our knowledge, this is the first report of M. javanica on Duboisia sp. in Brazil. This finding has great importance for Brazilian production since this nematode may damage plants, reduce yields, and control of this nematode on Duboisia sp. is difficult (5). Additional work is necessary in order to elucidate the losses caused by M. javanica on Duboisia sp.

References: (1) J. I. Bonetti and S. Ferraz. Fitopatol. Bras. 6:533, 1981. (2) P. R. Esbenshade and A. C. Triantaphyllou. J. Nematol. 22:10, 1990. (3) K. M. Hartman and J. N. Sasser. Page 115 in: An Advanced Treatise on Meloidogyne. Volume II Methodology. K. R. Barker et al., eds. North Carolina State University Graphics, Raleigh, 1985. (4) D. J. Hunt and Z. A. Handoo. Page 55 in: Root-Knot Nematodes. R. N. Perry et al., eds. CABI International, Wallingford, UK, 2010. (5) A. M. Mello et al. Nematol. Bras. 22(2):12, 1998.
Seed and seedling traits affecting critical life stage transitions and recruitment outcomes in dryland grasses
Authors: Larson Julie E. , Sheley Roger L. , Hardegree Stuart P. , Doescher Paul S. , James Jeremy J.
Published: September 2014

Seeding native plants is a key management practice to counter land degradation across the globe, yet the majority of seeding efforts fail, limiting our ability to accelerate ecosystem recovery.

Recruitment requires transitions through several seed and seedling stages, some of which may have overriding influences on restoration outcomes. We lack, however, a general framework to understand and predict differences in these critical demographic processes across species. Functional traits influence fitness, and consequently, trait variation could provide the basis for a framework to explain and predict variation in life stage transition probabilities.

We used seed and seedling traits, and field probabilities of germination, emergence, seedling establishment, and survival for 47 varieties of drylands grasses under two watering treatments to identify critical life stage transitions and quantify the effect of traits on cumulative survival through the first growing season.

Variation in germination and emergence probabilities explained over 90% of the variation in cumulative survival regardless of seedling survival probabilities or watering treatment, with emergence probability being the strongest predictor of cumulative survival.

Coleoptile tissue density and seed mass had significant effects on emergence and germination, respectively, explaining 10–23% of the variation in transition probabilities.

Synthesis and applications. While the majority of functional trait work has centred on linking leaf and root traits to resource acquisition and utilization, our study demonstrates that traits associated with germination and emergence may have prevailing influences on restoration outcomes. A portion of these traits have been examined, but there is substantial opportunity to identify other key traits driving these demographic processes. These advancements will underpin our ability to develop trait‐based frameworks for overcoming recruitment barriers and facilitating recovery of degraded systems across the globe.
The Amherst Embassy and British Discoveries in China
Authors: Hao Gao
Published: September 2014

The Amherst embassy to China has long been viewed as a major diplomatic failure in Britain's early relations with China. This article concentrates on the greatly overlooked aspect of the Amherst mission: the delegation's discoveries in China after the official proceedings were concluded. Since the embassy was given unprecedented freedom of movement during its four‐month return journey from Beijing to Canton, British observers were able to explore the interior of China and to communicate more fully with the Chinese government and people than ever before. As a consequence, the Amherst embassy not only provided valuable first‐hand observations which increased and improved Britain's knowledge of China, but developed the view that the Qing government was the chief obstacle to the progress of Chinese civilization and to the general welfare of the Chinese people. These important perceptions laid the foundation for future changes in Sino‐British relations and led, indirectly, to the outbreak of the Opium War.
Eighteenth‐CenturyJamaica's Ambivalent Cosmopolitanism
Authors: Robertson James
Published: September 2014

Eighteenth‐centuryJamaica's brutal society appears inimical to the values that theEnlightenment promoted, yetEnlightenment‐era scientific inquiry, printing and some self‐critical debates took place in the island's towns. Sugar‐profits could fund books and instruments.Jamaica's eighteenth‐century towns sustained a social life that allowed wider aspects ofEnlightenment‐era cosmopolitanism to take root. In these transient societies ‘ordinaries’ and coffee‐houses stocked the latest newspapers, while the new Freemasons’ lodges integrated the colony's white males. The urban networks of assembly rooms, journal subscriptions and scientific memberships inKingston andSpanishTown were inclusive – for those whites who could afford them – while some basic research did draw on enslaved plant collectors’ expertise. Data fromWestIndian botanists and historians informedEuropean scholars’ theorizing, but for slave‐holding Jamaicans the humanitarian ideas developed in mid‐eighteenth‐century Europe proved a tendentious import. In the 1780s the firstMethodist missionaries, the next metropolitan intellectual wave to reach the island, piggy‐backed onto existing urban intellectual networks before reaching out to a widerJamaica. By the century's end a fearful colonial elite found the Enlightenment's free exchange of ideas suspicious rather than supportive.
From special tasks to extensive roles: the changing face of special needs teachers in Finnish vocational further education
Authors: Pirttimaa Raija , Hirvonen Maija
Published: September 2014

Following the development of inclusive education in vocational education and training (VET), the discussion about the prevention of marginalisation and dropouts has increased. At the same time, the formal education system has strengthened the position of support services, such as special educational needs (SEN) teachers, social workers and counsellors. However, a confusion of roles in the work of SEN teachers seems evident. The changing work of SEN teachers has not been of great research interest in Finland. The focus has been mainly on SEN teachers at the secondary school level (Kivirauma and Kuorelahti, 2002; Ström, 1999). The work of vocational SEN teachers has been studied by Kaikkonen, 2010 and Hirvonen, 2006. SEN teachers comprise two groups in the field: one group supports vocational subjects and the other group supports general subjects. The aim of this study is to determine how SEN teachers of general subjects define the objectives of their work and how they organise pedagogical support. Ten SEN teachers in vocational colleges were interviewed. A qualitative analysis was performed. The main findings showed, on the one hand, an autonomous position and, on the other, a work model that can be described as a ‘traditional special needs education model’. However, the findings showed that the autonomous role was contradictory. SEN teachers did not emphasise the connection with the VET community or college‐based guidelines and directions. Moreover, although the consultative role exists, the findings showed that it is not a regular part of the work of SEN teachers.
The case for frequency sensitivity in orthographic learning
Authors: McMurray Sharon , McVeigh Claire
Published: September 2014

This paper positions the importance of frequency sensitivity in the development of orthographic knowledge throughout childhood and promotes learning to spell as a vehicle which may be used effectively to develop this sensitivity. It is suggested that orthographic knowledge is advanced via a process of ‘frequency sensitivity’ to ‘patterns and sequences’ and ‘rules and regularities’ particular to English orthography and that the process of sensitivity to these coarse grain orthographic patterns is influenced by consistency in sound and by morphological knowledge (knowledge of morphemes; words or word parts that form the smallest unit of meaning in language). A model highlighting the increasing importance of orthography and morphology as reading and spelling development progresses is presented. Discussion of the importance of considering phonology, orthography and morphology throughout literacy development and the relative importance of each is discussed. Distinctions are drawn between the processes involved in children who are good readers and good spellers, children who are good readers and poor spellers, and children who are poor readers and poor spellers. This paper outlines how considering these interrelated and developmentally sensitive contributors to literacy development can contribute to the practice of educational professionals in promoting the development of literacy skills throughout childhood.
Evaluating Area‐Based Socioeconomic Status Indicators for Monitoring Disparities within Health Care Systems: Results from a Primary Care Network
Authors: Berkowitz Seth A. , Traore Carine Y. , Singer Daniel E. , Atlas Steven J.
Published: September 2014

Objective

To determine which area‐based socioeconomic status (SES) indicator is best suited to monitor health care disparities from a delivery system perspective.

Data Sources/Study Setting

142,659 adults seen in a primary care network from January 1, 2009 to December 31, 2011.

Study Design

Cross‐sectional, comparing associations between area‐based SES indicators and patient outcomes.

Data Collection

Address data were geocoded to construct area‐based SES indicators at block group (BG), census tract (CT), and ZIP code (ZIP) levels. Data on health outcomes were abstracted from electronic records. Relative indices of inequality (RIIs) were calculated to quantify disparities detected by area‐based SES indicators and compared to RIIs from self‐reported educational attainment.

Principal Findings

ZIP indicators had less missing data than BG or CT indicators (p < .0001). Area‐based SES indicators were strongly associated with self‐report educational attainment (p < .0001). ZIP, BG, and CT indicators all detected expected SES gradients in health outcomes similarly. Single‐item, cut point defined indicators performed as well as multidimensional indices and quantile indicators.

Conclusions

Area‐based SES indicators detected health outcome differences well and may be useful for monitoring disparities within health care systems. Our preferred indicator was ZIP‐level median household income or percent poverty, using cut points.
Assessing the impact of arthropod natural enemies on crop pests at the field scale
Authors: Macfadyen Sarina , Davies Andrew P. , Zalucki Myron P.
Published: September 2014

There are many reasons why it is important that we find ways to conserve, and better utilize natural enemies of invertebrate crop pests. Currently, measures of natural enemy impact are rarely incorporated into studies that purport to examine pest control. Most studies examine pest and natural enemy presence and/or abundance and then qualitatively infer impact. While this provides useful data to address a range of ecological questions, a measure of impact is critical for guiding pest management decision‐making. Often some very simple techniques can be used to obtain an estimate of natural enemy impact. We present examples of field‐based studies that have used cages, barriers to restrict natural enemy or prey movement, direct observation of natural enemy attack, and sentinel prey items to estimate mortality. The measure of natural enemy impact used in each study needs to be tailored to the needs of farmers and the specific pest problems they face. For example, the magnitude of mortality attributed to natural enemies may be less important than the timing and consistency of that mortality between seasons. Tailoring impact assessments will lead to research outcomes that do not simply provide general information about how to conserve natural enemies, but how to use these natural enemies as an integral part of decision‐making.
Heat and Mass Transport during Microwave Heating of Mashed Potato in Domestic Oven—Model Development, Validation, and Sensitivity Analysis
Authors: Chen Jiajia , Pitchai Krishnamoorthy , Birla Sohan , Negahban Mehrdad , Jones David , Subbiah Jeyamkondan
Published: September 2014

A 3‐dimensional finite‐element model coupling electromagnetics and heat and mass transfer was developed to understand the interactions between the microwaves and fresh mashed potato in a 500 mL tray. The model was validated by performing heating of mashed potato from 25 °C on a rotating turntable in a microwave oven, rated at 1200 W, for 3 min. The simulated spatial temperature profiles on the top and bottom layer of the mashed potato showed similar hot and cold spots when compared to the thermal images acquired by an infrared camera. Transient temperature profiles at 6 locations collected by fiber‐optic sensors showed good agreement with predicted results, with the root mean square error ranging from 1.6 to 11.7 °C. The predicted total moisture loss matched well with the observed result. Several input parameters, such as the evaporation rate constant, the intrinsic permeability of water and gas, and the diffusion coefficient of water and gas, are not readily available for mashed potato, and they cannot be easily measured experimentally. Reported values for raw potato were used as baseline values. A sensitivity analysis of these input parameters on the temperature profiles and the total moisture loss was evaluated by changing the baseline values to their 10% and 1000%. The sensitivity analysis showed that the gas diffusion coefficient, intrinsic water permeability, and the evaporation rate constant greatly influenced the predicted temperature and total moisture loss, while the intrinsic gas permeability and the water diffusion coefficient had little influence.
Computational Fluid Dynamics Approaches in Quality and Hygienic Production of Semisolid Low‐Moisture Foods: A Review of Critical Factors
Authors: Mondal Arpita , Buchanan Robert L. , Lo Y. Martin
Published: September 2014

Low‐moisture foods have been responsible for a number of salmonellosis outbreaks worldwide over the last few decades, with cross contamination from contaminated equipment being the most predominant source. To date, actions have been focused on stringent hygienic practices prior to production, namely periodical sanitization of the processing equipment and lines. Not only does optimum sanitization require in‐depth knowledge on the type and source of contaminants, but also the heat resistance of microorganisms is unique and often dependent on the heat transfer characteristics of the low‐moisture foods. Rheological properties, including viscosity, degree of turbulence, and flow characteristics (for example, Newtonian or non‐Newtonian) of both liquid and semisolid foods are critical factors impacting the flow behavior that consequently interferes heat transfer and related control elements. The demand for progressively more accurate prediction of complex fluid phenomena has called for the employment of computational fluid dynamics (CFD) to model mass and heat transfer during processing of various food products, ranging from drying to baking. With the aim of improving the quality and safety of low‐moisture foods, this article critically reviewed the published literature concerning microbial survival in semisolid low‐moisture foods, including chocolate, honey, and peanut butter. Critical rheological properties and state‐of‐the‐art CFD application relevant to quality production of those products were also addressed. It is anticipated that adequate prediction of specific transport properties during optimum sanitization through CFD could be used to solve current and future food safety challenges.
Minnesota Multiphasic Personality Inventory profile in patients with restless legs syndrome
Authors: Turkel Yakup , Oguzturk Omer , Dag Ersel , Buturak S. Visal , Ekici Mehmet S.
Published: September 2014

Introduction

Restless legs syndrome (RLS) is associated with psychiatric disorders. We aim to investigate the personality traits of RLS patients using the Minnesota Multiphasic Personality Inventory.

Methods

Twenty adult patients with RLS (14 females and 6 males) and 20 healthy controls (14 females and 6 males) who were referred to university neurology were enrolled in the present study. Diagnosis of RLS was established using International Restless Legs Syndrome Study Group. Psychometric evaluation was made with the Turkish version of the Minnesota Multiphasic Personality Inventory.

Results

RLS patients have significantly higher absolute and clinical elevation scores on hypochondriasis and hysteria, and clinical elevation scores on psychasthenia, compared with the controls. Absolute scores on depression were higher at the border in RLS patients compared with the controls.

Discussion

RLS patients have hypochondriac, hysterical, depressive, and anxious personality traits.
Spatio‐Temporal Expression of Peroxisome Proliferator‐Activated Receptor α During Human Prenatal Development
Authors: Cizkova Katerina , Rajdova Aneta , Ehrmann Jiri
Published: September 2014

Peroxisome proliferator‐activated receptor α (PPARα) is a ligand‐dependent transcription factor which is activated by various endogenous as well as exogenous compounds. It is involved in the regulation of a variety of biological processes, such as nutrient metabolism, energy homoeostasis, immunological response and xenobiotic metabolism. Little is known about its expression during human prenatal development. We examined the spatio‐temporal expression pattern of PPARα in human embryonic/foetal intestines, liver and kidney from the 5th to 20th week of prenatal life by indirect two‐step immunohistochemistry. PPARα expression can already be detected in the early stages of prenatal development; as early as the 7th week of intrauterine development (IUD) in the intestines, 5th week of IUD in the liver and 6th week of IUD in the kidney. We found age‐dependent changes in the PPARα expression pattern in the intestines and kidney. These events occur approximately at the commencement of function of these organs. In the intestines, we detected an obvious change of the PPARα expression pattern along the crypt‐villous axis in the 11th week of IUD. In the kidney, the most apparent change was increased expression of PPARα in glomeruli in the 12th week of IUD. Moreover, in the liver, we detected a strong positivity in part of the developing blood elements. Information about the spatio‐temporal expression pattern of PPARα could be the first step in evaluating the potential harmful impact of a wide range of environmental or pharmaceutical compounds which serve as PPARα ligands on the developing human organism.
Case-Base Methods for Studying Vaccination Safety
Authors: Saarela Olli , Hanley James A.
Published: September 2014

Pooling of controls under nested-case control settings can produce substantial efficiency gains compared to standard time-matched analysis using the Mantel–Haenszel method or conditional logistic regression. In the context of possible adverse effects of early childhood vaccinations, we propose pooling of the information from the controls to estimate the population exposure prevalence as a parametric or nonparametric function of time, and possibly other factors. This function in turn may be used as a plug-in estimate to control for confounding in the subsequent estimation of rate ratios. We derive standard errors for the resulting two-step estimators, demonstrate through simulations the efficiency gains compared to standard matched analysis, and propose a novel graphical presentation of the vaccination and adverse event time data. We formulate the methods in the general framework of case-base sampling, which subsumes the different case-control and case-only methods.
Salvage micro‐dissection testicular sperm extraction; outcome in men with non‐obstructive azoospermia with previous failed sperm retrievals
Authors: Kalsi Jas S. , Shah Paras , Thum Yau , Muneer Asif , Ralph David J. , Minhas Suks
Published: September 2014

Objective

To assess the outcome of micro‐dissection testicular exploration sperm extraction (m‐TESE) as a salvage treatment in men with non‐obstructive azoospermia (NOA) in whom no sperm was previously found on single/multiple TESE or testicular sperm aspiration (TESA).

Patients and Methods

In all, 58 men with NOA underwent m‐TESE. All the patients had previously undergone either single/multiple TESE or TESA with no sperm found. All the patients underwent an m‐TESE using a standard technique. Serum follicle‐stimulating hormone (FSH), testosterone and histopathological diagnosis were examined as predictive factors for sperm recovery. All patients underwent preoperative genetic screening. One patient was found to have an azoospermic factor c (AZFc) micro‐deletion and five were diagnosed with Kleinfelter's syndrome.

Results

The mean (range) patient age was 39.0 (26–57) years. Spermatozoa were successfully retrieved in 27 men by m‐TESE (46.5%). The mean (range) FSH level was 19.4 (1.6–58.5) IU/L. There was no correlation in age (mean age retrieved 38.1 years, not retrieved 39.7 years, P = 0.38), FSH levels (mean FSH retrieved 21.4 IU/L, not retrieved 17.7 IU/L, P = 0.3) and the ability to find sperm by m‐TESE. However, there was a significant difference in testosterone levels and sperm retrieval (mean testosterone retrieved 14.99 nmol/L, not retrieved 11.39 nmol/L, P < 0.05). Patients with a diagnosis of Sertoli‐cell‐only (SCO) syndrome [14/35 (40%)] and maturation arrest [four of 11 (36%)] had lower sperm retrieval rates than those in the hypospermatogenesis group [nine of 12 (75.0%)] (P < 0.05). There were no significant complications after m‐TESE.

Conclusions

In men with NOA who have undergone previous attempts at sperm retrieval with negative results, a salvage m‐TESE offers a significant chance of finding sperm even in SCO syndrome. There does seem to be a correlation between preoperative testosterone levels and the ability to successfully find sperm.
Trifecta and optimal perioperative outcomes of robotic and laparoscopic partial nephrectomy in surgical treatment of small renal masses: a multi‐institutional study
Authors: Zargar Homayoun , Allaf Mohamad E. , Bhayani Sam , Stifelman Michael , Rogers Craig , Ball Mark W. , Larson Jeffrey , Marshall Susan , Kumar Ramesh , Kaouk Jihad H.
Published: September 2014

Objective

To compare the perioperative outcomes of robotic partial nephrectomy (RPN) with laparoscopic PN (LPN) performed for small renal masses (SRMs), in a large multi‐institutional series and to define a new composite outcome measure, termed ‘optimal outcome’ for the RPN group.

Patients and Methods

Retrospective review of 2392 consecutive cases of RPN and LPN performed in five high‐volume centres from 2004 to mid‐2013. We limited our study to SRMs and cases performed by surgeons with significant expertise with the technique. The Trifecta was defined as negative surgical margin, zero perioperative complications and a warm ischaemia time of ≤25 min. The ‘optimal outcome’ was defined as achievement of Trifecta with addition of 90% estimated glomerular filtration rate preservation and no chronic kidney disease stage upgrading. Univariable and multivariable analysis were used to identify factors predicting Trifecta and ‘optimal outcome’ achievement.

Results

In all, 1185 RPN and 646 LPN met our inclusion criteria. Patients in the RPN group were older and had a higher median Charlson comorbidity index and higher R.E.N.A.L. nephrometry score. The RPN group had lower warm ischaemia time (18 vs 26 min), overall complication rate (16.2% vs 25.9%), and positive surgical margin rate (3.2% vs. 9.7%). There was a significantly higher Trifecta rate for RPN (70% vs 33%) and the rate of achievement of ‘optimal outcome’ for the RPN group was 38.5%.

Conclusions

In this large multi‐institutional series RPN was superior to LPN for perioperative surgical outcomes measured by Trifecta. Patients in the RPN group had better outcomes for all three components of Trifecta compared with their LPN counterparts. Our more strict definition for ‘optimal outcome’ might be a better tool for assessing perioperative and functional outcomes after minimally invasive PN. This tool needs to be externally validated.
YM155 down‐regulates survivin and XIAP, modulates autophagy and induces autophagy‐dependent DNA damage in breast cancer cells
Authors: Cheng S M , Chang Y C , Liu C Y , Lee J Y C , Chan H H , Kuo C W , Lin K Y , Tsai S L , Chen S H , Li C F , Leung E , Kanwar J R , Huang C C , Chang J Y , Cheung C H A
Published: September 2014

Background and Purpose

The aim of this study was to determine the potency and molecular mechanism of action of YM155, a first‐in‐class survivin inhibitor that is currently under phase I/II clinical investigations, in various drug‐resistant breast cancers including the oestrogen receptor positive (ER+) tamoxifen‐resistant breast cancer and the caspase‐3‐deficient breast cancer.

Experimental Approach

The potency of YM155 in SK‐BR‐3, MDA‐MB‐231, MCF7 and its tamoxifen‐resistant sublines, TamR6, TamR7, TamR8, TamC3 and TamC6, were determined by MTT assay. Western blot analysis, flow cytometric analysis, reverse transcription‐PCR, fluorescent microscopy and comet assay were used to determine the molecular mechanism of action of YM155 in different breast cancer cell lines.

Key Results

YM155 was equally potent towards the parental ER+/caspase‐3‐deficient MCF7 breast cancer cells and its tamoxifen‐resistant sublines in vitro. The ER−/HER2+ SK‐BR‐3 breast cancer cells and the triple‐negative/caspase‐3‐expressing metastatic aggressive MDA‐MB‐231 breast cancer cells were also sensitive to YM155 with IC50 values in the low nanomolar range. Targeting survivin by YM155 modulated autophagy, induced autophagy‐dependent caspase‐7 activation and autophagy‐dependent DNA damage in breast cancer cells. Interestingly, YM155 also induced XIAP degradation and the degradation of XIAP might play an important role in YM155‐induced autophagy in breast cancer cells.

Conclusions and Implications

YM155 is a potent survivin inhibitor that has potential for the management of various breast cancer subtypes regardless of the expression of ER, HER2 and caspase‐3. Importantly, this study provides new insights into YM155's molecular mechanism of action and therapeutic potential in the treatment of tamoxifen‐resistant breast cancer.
Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics
Authors: Cook A E , Mistry S N , Gregory K J , Furness S G B , Sexton P M , Scammells P J , Conigrave A D , Christopoulos A , Leach K
Published: September 2014

Background and Purpose

Clinical use of cinacalcet in hyperparathyroidism is complicated by its tendency to induce hypocalcaemia, arising partly from activation of calcium‐sensing receptors (CaS receptors) in the thyroid and stimulation of calcitonin release. CaS receptor allosteric modulators that selectively bias signalling towards pathways that mediate desired effects [e.g. parathyroid hormone (PTH) suppression] rather than those mediating undesirable effects (e.g. elevated serum calcitonin), may offer better therapies.

Experimental Approach

We characterized the ligand‐biased profile of novel calcimimetics in HEK293 cells stably expressing human CaS receptors, by monitoring intracellular calcium (Ca2+i) mobilization, inositol phosphate (IP)1 accumulation, ERK1/2 phosphorylation (pERK1/2) and receptor expression.

Key Results

Phenylalkylamine calcimimetics were biased towards allosteric modulation of Ca2+i mobilization and IP1 accumulation. S,R‐calcimimetic B was biased only towards IP1 accumulation. R,R‐calcimimetic B and AC‐265347 were biased towards IP1 accumulation and pERK1/2. Nor‐calcimimetic B was unbiased. In contrast to phenylalkylamines and calcimimetic B analogues, AC‐265347 did not promote trafficking of a loss‐of‐expression, naturally occurring, CaS receptor mutation (G670E).

Conclusions and Implications

The ability of R,R‐calcimimetic B and AC‐265347 to bias signalling towards pERK1/2 and IP1 accumulation may explain their suppression of PTH levels in vivo at concentrations that have no effect on serum calcitonin levels. The demonstration that AC‐265347 promotes CaS receptor receptor signalling, but not trafficking reveals a novel profile of ligand‐biased modulation at CaS receptors The identification of allosteric modulators that bias CaS receptor signalling towards distinct intracellular pathways provides an opportunity to develop desirable biased signalling profiles in vivo for mediating selective physiological responses.
Health and functioning in the everyday lives of young children with cancer: documenting with the International Classification of Functioning, Disability and Health – Children and Youth (ICF‐CY)
Authors: Darcy L. , Enskär K. , Granlund M. , Simeonsson R. J. , Peterson C. , Björk M.
Published: September 2014

Background

Health care focus is shifting for children from surviving childhood cancer to living with it on a daily basis. There is a need to document health and function in the everyday lives of young children with cancer using the multidimensional framework and language of the International Classification of Functioning, Disability and Health – Children and Youth (ICF‐CY).

Aims

The aims of this study were (1) to document health and functioning in the everyday lives of young children with cancer using ICF‐CY codes and (2) to identify a comprehensive code set that can aid clinical assessment.

Method

Interviews with children diagnosed with cancer and their parents, were transcribed, reviewed for content and coded to the ICF‐CY using linking procedures.

Results

A comprehensive code set (n = 70) for childhood cancer was identified. The majority of content identified to codes was related to activity and participation describing social relations with family, peers and professionals, preschool attendance and play, as well as issues related to support and independence.

Conclusions

The ICF‐CY can be used to document the nature and range of characteristics and consequences of cancer experienced by children. The identified comprehensive code set could be helpful to health care professionals, parents and teachers in assessing and supporting young children's health and everyday life through the cancer trajectory. The comprehensive code set could be developed as a clinical assessment tool for those caring for young children with cancer. The universal language of the ICF‐CY means that the utility of a clinical assessment tool based on identified codes can have wide reaching effects for the care of young children with cancer.
Early risk factors for pubertal asthma
Authors: Hovland V. , Riiser A. , Mowinckel P. , Carlsen K.‐H. , Lødrup Carlsen K. C.
Published: September 2014

Background

Early life risk factors are previously described for childhood asthma, but less is known related to asthma in adolescence. We aimed to investigate early risk factors (before 2 years) for pubertal asthma and secondarily for pubertal asthma phenotypes based upon allergic comorbidities.

Methods

Based on data from 550 adolescents in the prospective birth cohort ‘Environment and Childhood Asthma’ study, subjects were categorized by recurrent bronchial obstruction (rBO) 0–2 years, asthma 2–10 years, and pubertal asthma from 10 to 16 years including incident asthma in puberty and asthma in remission from 10 to 16 years or as never rBO/asthma 0–16 years. Asthma in puberty was further classified based on the comorbidities atopic dermatitis and allergic rhinitis (AR) from 10 to 16 years. Twenty‐three common asthma risk factors identified by 2 years of age, including frequency and persistence of bronchial obstruction (severity score), were analysed by weighted logistic regression for each phenotype.

Results

In adjusted models, the risk of pubertal asthma increased significantly with higher severity score, parental rhinitis, being the firstborn child, and familial stress around birth. Pubertal asthma in remission was significantly associated with severity score and number of lower respiratory tract infections and inversely associated with breastfeeding beyond 4 months. Pubertal incident asthma was more common among firstborn children. All asthma phenotypes with allergic diseases were significantly associated with severity score, whereas familial perinatal stress increased the risk of asthma only. Asthma combined with AR was associated with parental asthma and being firstborn, whereas the risk of asthma with both atopic dermatitis and AR increased with higher paternal education, atopic dermatitis, being firstborn, and familial perinatal stress.

Conclusion and clinical relevance

Important early risk factors for pubertal asthma were early airways obstruction, parental rhinitis, being the firstborn child, and perinatal familial stress.
T-bet regulates differentiation of forkhead box protein 3+ regulatory T cells in programmed cell death-1-deficient mice
Authors: Tahara M , Kondo Y , Yokosawa M , Tsuboi H , Takahashi S , Shibayama S , Matsumoto I , Sumida T
Published: September 2014

Programmed cell death-1 (PD-1) plays an important role in peripheral T cell tolerance, but whether or not it affects the differentiation of helper T cell subsets remains elusive. Here we describe the importance of PD-1 in the control of T helper type 1 (Th1) cell activation and development of forkhead box protein 3 (FoxP3+) regulatory T cells (Tregs). PD-1-deficient T cell-specific T-bet transgenic (P/T) mice showed growth retardation, and the majority died within 10 weeks. P/T mice showed T-bet over-expression, increased interferon (IFN)-γ production by CD4+T cells and significantly low FoxP3+Treg cell percentage. P/T mice developed systemic inflammation, which was probably induced by augmented Th1 response and low FoxP3+Treg count. The study identified a unique, previously undescribed role for PD-1 in Th1 and Treg differentiation, with potential implication in the development of Th1 cell-targeted therapy.
Detecting somatic mosaicism: considerations and clinical implications
Authors: Cohen A.S.A. , Wilson S.L. , Trinh J. , Ye X.C.
Published: September 2014

Human disease is rarely a matter of all or nothing; variable expressivity is generally observed. Part of this variability is explained by somatic mosaicism, which can arise by a myriad of genetic alterations. These can take place at any stage of development, possibly leading to unusual features visible at birth, but can also occur later in life, conceivably leading to cancer. Previously, detection of somatic mosaicism was extremely challenging, as many gold standard tests lacked the necessary resolution. However, with the advances in high‐throughput sequencing, mosaicism is being detected more frequently and at lower levels. This raises the issue of normal variation within each individual vs mosaicism leading to disease, and how to distinguish between the two. In this article, we will define somatic mosaicism with a brief overview of its main mechanisms in concrete clinical examples, discuss the impact of next‐generation sequencing technologies in its detection, and expand on the clinical implications associated with a discovery of somatic mosaicism in the clinic.
Accuracy of computer‐guided implantation in a human cadaver model
Authors: Yatzkair Gustavo , Cheng Alice , Brodie Stan , Raviv Eli , Boyan Barbara D. , Schwartz Zvi
Published: September 2014

Objectives

To examine the accuracy of computer‐guided implantation using a human cadaver model with reduced experimental variability.

Materials and methods

Twenty‐eight (28) dental implants representing 12 clinical cases were placed in four cadaver heads using a static guided implantation template. All planning and surgeries were performed by one clinician. All radiographs and measurements were performed by two examiners. The distance of the implants from buccal and lingual bone and mesial implant or tooth was analyzed at the apical and coronal levels, and measurements were compared to the planned values.

Results

No significant differences were seen between planned and implanted measurements. Average deviation of an implant from its planning radiograph was 0.8 mm, which is within the range of variability expected fromCTanalysis.

Conclusions

Guided implantation can be used safely with a margin of error of 1 mm.
Influence of local administration of pamidronate on extraction socket healing – a histomorphometric proof‐of‐principle pre‐clinical in vivo evaluation
Authors: Fischer Kai R. , Stavropoulos Andreas , Calvo‐Guirado José‐Luis , Schneider David , Fickl Stefan
Published: September 2014

Objectives

To evaluate the influence of local administration of pamidronate histomorphometrically, adsorbed on a collagenated porcine bone substitute, on extraction socket healing.

Material and methods

Two American Fox‐hound dogs were used within this proof‐of‐principle study. Following endodontic treatment of the distal root of the three lower premolars, the teeth were hemisected, and the mesial roots were extracted flapless. The sockets were then loosely filled, in a split‐mouth fashion, with a collagenated porcine bone substitute (Osteobiol Gen‐Os; CPB), rehydrated either with 90 mg/ml pamidronate (Aredia®; test) or with sterile saline (control). Extraction sockets were sealed with connective tissue punches obtained from the palate and secured with sutures. After 4 months of healing, specimens containing the socket sites and remaining roots were retrieved and histomorphometrically examined.

Results

Histological evaluation of the sections revealed substantial differences in healing patterns. Control sites presented with various amounts of newly formed bone and no evidence of CPB inside the socket; in contrast, limited amounts of bone were observed at test sites, which were filled with CPB mainly embedded in connective tissue. Only minor differences were observed between test and control sites regarding vertical bone loss (buccal bone: −1.01 mm vs. −1.15 mm; lingual bone: −0.92 mm vs. −1.15 mm). Horizontal bone loss was nearly three times higher in control sites comparing to sites treated with pamidronate (−2.19 ± 1.81 mm vs. −0.80 ± 0.91 mm) at a level corresponding to 3 mm below the cemento‐enamel junction (CEJ).

Conclusion

Local administration of pamidronate adsorbed on a collagenated porcine bone substitute in particulate form appeared to delay extraction socket healing, but may also reduce post‐extraction dimensional changes in terms of horizontal bone width. Additionally, pamidronate appears to obstruct resorption of the porcine bone substitute.
Respiratory Hemodynamics in the Hepatic Veins—Normal Pattern
Authors: Fadel Bahaa M. , Alkalbani Ahmad , Husain Aysha , Dahdouh Ziad , Di Salvo Giovanno
Published: September 2014

Doppler interrogation of blood flow in the hepatic veins (HVs) is a part of any comprehensive echocardiographic examination. Data derived from the HV Doppler provide a useful tool for the assessment of right heart function. Beyond its dependence on the cardiac cycle, right heart hemodynamics, and compliance of the liver parenchyma, blood flow in the HVs is influenced by the respiratory cycle. Systematic analysis of the behavior of the HV Doppler during respiration allows one to recognize normal and abnormal flow‐patterns and distinguish among various disease states that involve the right heart. In this manuscript we discuss the effect of respiration on the HV Doppler in individuals with normal right heart function.