bluuebunny/crossref_metadata_2025 huggingface dataset:
Who Are All These People? Longitudinal Changes in New Employee Social Networks Within a State Agency
Authors: Hatmaker Deneen M. , Park Hyun Hee
Published: April 2013

Organizational socialization is the process by which newcomers adapt to their organization and learn how to become productive organizational members. Organizations employ tactics such as classroom training, mentoring, orientation sessions, and on-the-job training to assist new employees in their transition. At the same time, newcomers engage in their own proactive efforts to seek information and establish ties with experienced organizational members who have access to valued resources. While scholarship has noted the importance of both socialization and employee intraorganizational networks within public sector organizations, little research has focused on these areas. This article links the organizational socialization and social network frameworks by examining how the networks of new employees in a state agency change over time. Based on our findings, we offer implications for rewarding core advisors, mentoring programs, and fostering interactions between newcomers and experienced organizational members.
Outcomes of Repeat Revision Anterior Cruciate Ligament Reconstruction
Authors: Griffith Timothy B. , Allen Benjamin J. , Levy Bruce A. , Stuart Michael J. , Dahm Diane L.
Published: April 2013

Background:

As anterior cruciate ligament (ACL) reconstruction is performed increasingly in the United States, the rate of revision ACL reconstruction continues to rise. A paucity of literature exists with respect to repeat ACL revision surgery.

Purpose:

To evaluate the functional outcomes of patients who had undergone at least 2 revision ACL reconstructions.

Study Design:

Case series; Level of evidence, 4.

Methods:

The records of all patients who had undergone repeat revision ACL reconstructions between 1998 and 2009 were retrospectively reviewed. Data collected included patient demographics, operative findings, pre- and postoperative physical examination findings, radiographs, and Tegner, Lysholm, and International Knee Documentation Committee (IKDC) subjective scores.

Results:

Fifteen patients had undergone repeat revision ACL reconstruction during the study period. Mean age was 27 years (range, 18-57 years). Mean follow-up was 5 years (range, 2-10 years). At the time of repeat revision surgery, new tunnels were drilled in 9 of 15 (60%) cases. Of those, 8 of 9 (89%) were drilled because femoral tunnels were deemed “too anterior.” During repeat revision, 11 of 15 (73%) patients were noted to have a meniscal tear, and 9 of 15 (67%) had International Cartilage Repair Society (ICRS) grade 3 or 4 chondral lesions. Mean Lysholm score was 60 preoperatively and increased to 82 postoperatively ( P < .001). Mean preoperative IKDC score was 59, which increased to 80 postoperatively ( P < .001). Mean preoperative Tegner score was 6.0. Mean postoperative Tegner score was 4.5, with only 4 of 15 (27%) patients having returned to their prior activity level ( P < .001). Two patients (13%) sustained a traumatic rerupture. Presence of grade 3 or 4 chondral lesions and body mass index greater than 28 at the time of repeat revision were associated with a “fair” or “poor” outcome by Lysholm score ( P = .007 and P = .03, respectively) and IDKC subjective scoring ( P = .04 and P = .007, respectively).

Conclusion:

Repeat revision ACL reconstruction may improve the functional outcomes of patients who have failed revision ACL reconstruction. Most patients do not return to prior activity level following repeat revision. Presence of grade 3 or 4 chondral lesions and body mass index greater than 28 were associated with worse outcomes.
Partial Trisomy 13 and Partial Monosomy 8 Mosaicism Secondary to an Unbalanced De Novo Translocation
Authors: Baranello Giovanni , Cesaretti Claudia , Zambonin Fabio , Casalone Rosario , Granata Paola , Esposito Silvia , Alfei Enrico , Natacci Federica
Published: April 2013

Few cases of mosaicism involving a normal cell line and an unbalanced autosomal translocation have been reported so far. No cases of partial trisomy 13 and partial monosomy 8 mosaicism have been published. The authors report a new patient with partial trisomy 13 and partial monosomy 8 mosaicism due to an unbalanced translocation (13/8). A postzygotic mitotic exchange of nonhomologous chromatids followed by the loss of one of the translocated chromatids has been hypothesized as the potential underlying mechanism. Although a clear correlation of the clinical features of the patient with his chromosomal abnormality can be challenging, dysmorphic features, hyperactive behavior, moderate developmental delay, and tonic-clonic seizures can be interpreted as secondary to the particular genotype of the patient. These findings should be taken into account in the diagnostic process of patients presenting with multiple congenital anomalies and/or mental retardation conditions.
Education and Support for Fathers Improves Breastfeeding Rates
Authors: Maycock Bruce , Binns Colin W. , Dhaliwal Satvinder , Tohotoa Jenny , Hauck Yvonne , Burns Sharyn , Howat Peter
Published: April 2013

Background:

Studies have identified numerous factors affecting breastfeeding initiation and duration, including maternal education, mode of delivery, birth weight, socioeconomic status, and support of the infant’s father.

Objective:

The objective was to investigate the effects of an antenatal education session and postnatal support targeted to fathers.

Methods:

The Fathers Infant Feeding Initiative (FIFI Study) is a randomized controlled trial to increase the initiation and duration of breastfeeding that was conducted in 8 public maternity hospitals in Perth, Western Australia. A total of 699 couples were randomized within hospitals to either intervention or control groups. The intervention consisted of a 2-hour antenatal education session and postnatal support provided to fathers.

Results:

The any breastfeeding rate for the intervention group was significantly greater at 6 weeks: 81.6% in the intervention group compared to 75.2% in the control group, odds ratio 1.46 (95% CI, 1.01-2.13). After adjustment for age and hospital, the odds ratio for any breastfeeding in the intervention group was 1.58 (1.06-2.35) and for socioeconomic status (SES), 1.56 (1.06-2.30). The infants of older fathers were more likely to be breastfed at 6 weeks compared to infants of younger fathers ( P < .01), and infants of fathers with high SES more likely than infants of fathers with low SES ( P = .013).

Conclusion:

Even a small increase in breastfeeding rates brings public health benefits. In this study, a minimal intervention was found to significantly increase any breastfeeding at 6 weeks: 81.6% in the intervention group compared to 75.2% in the control group.
Associations of Hospital Staff Training and Policies with Early Breastfeeding Practices
Authors: Li Chuan-Ming , Li Ruowei , Ashley Cindy G. , Smiley Janice M. , Cohen Jennifer H. , Dee Deborah L.
Published: April 2013

Background:

In 2009, the Centers for Disease Control and Prevention implemented the Maternity Practices in Infant Nutrition and Care (mPINC) survey in all US birth facilities to assess breastfeeding-related maternity practices. Maternity practices and hospital policies are known to influence breastfeeding, and Alabama breastfeeding rates are very low.

Objective:

Our objective was to assess whether staff training and structural-organizational aspects of care, such as policies, were associated with infants’ breastfeeding behaviors 24 to 48 hours postpartum.

Methods:

We linked 2009 mPINC data from 48 Alabama hospitals with birth certificate and newborn screening databases. We used data collected 24 to 48 hours postpartum to classify 41 536 healthy, term, singleton infants as breastfed (any breast milk) or completely formula fed and examined associations with hospitals’ mPINC scores in comparison with the state mean. We conducted multilevel analyses to assess infants’ likelihood of being breastfed if their birth hospital scores were lower versus at least equal to the Alabama mean, accounting for hospital clustering, demographics, payment method, and prenatal care.

Results:

The odds of breastfeeding were greater in hospitals with a higher-than-state-mean score on the following: new employees’ breastfeeding education, nurses’ receipt of breastfeeding education in the past year, prenatal breastfeeding classes offered, having a lactation coordinator, and having a written breastfeeding policy. The number of recommended elements included in hospitals’ written breastfeeding policies was positively associated with newborn breastfeeding rates.

Conclusion:

Educating hospital staff to improve breastfeeding-related knowledge, attitudes, and skills; implementing a written hospital breastfeeding policy; and ensuring continuity of prenatal and postnatal breastfeeding education and support may improve newborn breastfeeding rates.
Controlling “Good Science”
Authors: Wells Celeste C.
Published: April 2013

This article addresses two intertwined aspects of difference that have yet to be deeply examined by organizational communication scholars—language and national identity. Accordingly, in this research, which is taken from a larger study on scientific occupational identity, I use Tompkins and Cheney’s enthymeme as an analytical device to explore the ways that participants reject and simultaneously instantiate discrimination in the workplace. In doing so, I contribute to the theory of occupational control by demonstrating how perceptions of language and national identity are used as part of occupational decision making in order to evaluate “good science” at work. Findings in this article indicate, regardless of the common assumptions that “science does not discriminate,” that the concept of good science is based, in part, on the identity of the embodied subject and his or her English language performance.
Stability prediction of milling process with variable pitch and variable helix cutters
Authors: Jin Gang , Zhang Qichang , Hao Shuying , Xie Qizhi
Published: April 2013

The use of variable pitch or helix cutters is a known means to prevent chatter vibration during milling. In this article, an alternative method based on an improved semi-discretization method is proposed to predict the stability of variable pitch or variable helix milling. In order to consider the effect of distributed system delays attributed to helix variation, the average delays were calculated for each flute after the engaged cutting flutes were divided into a finite number of axial elements. Meanwhile, a straightforward integral force model, which can consider the piecewise continuous regions of the cutting that describe the helix angle is used to determine the cutting force. Through comparisons with prior works, time-domain simulations, and cutting tests, the proposed approach was verified. In addition, the method was applied to examine the effect of tool geometries on stability trends. Several phenomena for certain combinations of pitch and helix angles are shown and explained.
A review of current automotive battery technology and future prospects
Authors: Budde-Meiwes Heide , Drillkens Julia , Lunz Benedikt , Muennix Jens , Rothgang Susanne , Kowal Julia , Sauer Dirk Uwe
Published: April 2013

In this article, today’s battery technologies and future options are discussed. Batteries have been one of the main focuses of automotive development in the last years. Technologies that have been in use for a very long time, such as the lead–acid battery, are indispensable but need improvement. New technologies such as the lithium-ion battery are entering the market. Supercapacitors (also known as electrochemical double-layer capacitors) can be used for high-power requirements such as regenerative braking. The variety of vehicles has increased with the introduction of hybrid vehicles, plug-in hybrid vehicles and electric vehicles and, for each type, suitable battery types are being used or under development. Appropriate battery system designs and charging strategies are needed. Battery technologies can be classified according to their energy density, their charge and discharge characteristics, system integration and the costs. Further relevant performance parameters are the calendar lifetime, the cycle lifetime, the low- and high-temperature performances and the safety.
Neural Evidence That Human Emotions Share Core Affective Properties
Authors: Wilson-Mendenhall Christine D. , Barrett Lisa Feldman , Barsalou Lawrence W.
Published: April 2013

Research on the “emotional brain” remains centered around the idea that emotions like fear, happiness, and sadness result from specialized and distinct neural circuitry. Accumulating behavioral and physiological evidence suggests, instead, that emotions are grounded in core affect—a person’s fluctuating level of pleasant or unpleasant arousal. A neuroimaging study revealed that participants’ subjective ratings of valence (i.e., pleasure/displeasure) and of arousal evoked by various fear, happiness, and sadness experiences correlated with neural activity in specific brain regions (orbitofrontal cortex and amygdala, respectively). We observed these correlations across diverse instances within each emotion category, as well as across instances from all three categories. Consistent with a psychological construction approach to emotion, the results suggest that neural circuitry realizes more basic processes across discrete emotions. The implicated brain regions regulate the body to deal with the world, producing the affective changes at the core of emotions and many other psychological phenomena.
Use of a commercial enzyme-linked immunosorbent assay for rapid detection of Giardia duodenalis in dog stools in the environment
Authors: Papini Roberto , Carreras Giulia , Marangi Marianna , Mancianti Francesca , Giangaspero Annunziata
Published: April 2013

Giardia duodenalis is considered a potentially zoonotic protozoan. Some animal species, including infected dogs, may play an important role in the spread of Giardia cysts through environmental contamination with their feces. In the present study, a commercial enzyme-linked immunosorbent assay (ELISA) was used to examine 143 samples of dog feces collected in urban areas as an indicator of the risk of field contamination. Using a Bayesian statistical approach, the ELISA showed a sensitivity of 88.9% and a specificity of 95.8% with positive and negative predictive values of 89.6% and 95.4%, respectively. The test affords the advantage of rapid processing of fecal samples without a complex technical structure and extensive costly labor. Moreover, the present results show that the assay provides public health veterinarians with a practical tool that can be used in screening programs, as a valid alternative or as an adjunct to other tests, in order to assess the biological risk of exposure to G. duodenalis cysts from dogs in human settlements. However, the test may not be completely accurate for human health risk evaluation, as it does not discriminate between zoonotic and non-zoonotic isolates.
Serum concentrations of canine alpha1-proteinase inhibitor in cobalamin-deficient Yorkshire Terrier dogs
Authors: Grützner Niels , Heilmann Romy M. , Bridges Cory S. , Suchodolski Jan S. , Steiner Jörg M.
Published: April 2013

Fecal canine alpha1-proteinase inhibitor (cα1-PI) concentration has been reported to be increased in dogs with protein-losing enteropathy due to the loss of cα1-PI into the gastrointestinal tract. A chronic loss of cα1-PI may theoretically deplete serum cα1-PI, potentially altering the proteinase-to-proteinase inhibitor balance. Protein-losing enteropathy has been reported to occur frequently in certain dog breeds such as Yorkshire Terriers and to be associated with hypocobalaminemia. The objective was to compare serum cα1-PI concentrations in Yorkshire Terriers with and without cobalamin (COB) deficiency. Serum samples from 52 COB-deficient and 69 normocobalaminemic Yorkshire Terriers, which had been submitted to the Gastrointestinal Laboratory (2008–2011; College Station, TX), were included retrospectively. Serum cα1-PI concentrations were measured using an in-house radioimmunoassay and compared between Yorkshire Terriers with and without COB deficiency using a Mann–Whitney U test. A Fisher exact test was used to evaluate whether a decreased serum cα1-PI concentration is associated with COB deficiency in Yorkshire Terriers. Serum cα1-PI concentrations were significantly lower in COB-deficient Yorkshire Terriers (median: 1,016 mg/l, range: 315–3,945 mg/l) than in normocobalaminemic Yorkshire Terriers (median: 1,665 mg/l, range: 900–2,970 mg/l; P < 0.0001). One-fourth ( n = 13) of the COB-deficient Yorkshire Terriers had a serum cα1-PI concentration below the lower limit of the reference interval (<732 mg/l), and COB deficiency was associated with decreased serum cα1-PI concentrations ( P < 0.0001). In the current study, serum cα1-PI concentrations are significantly lower in COB-deficient Yorkshire Terriers when compared to normocobalaminemic Yorkshire Terriers. Further studies are needed to determine the functional and potential prognostic implications of serum cα1-PI concentrations in dogs with gastrointestinal disease.
Step-Count Promotion Through a School-Based Intervention
Authors: Shore Stuart M. , Sachs Michael L. , DuCette Joseph P. , Libonati Joseph R.
Published: April 2013

The purpose was to determine the effects of a school-based pedometer intervention (SBPI) on daily accrued steps, academic performance, attendance, tardiness, and fitness performance in middle school students. Students from one, public middle school were assigned to a control ( n = 46) or a 6-week SBPI ( n = 46). Both groups recorded daily accrued pedometer steps. Grade point average (GPA), tardiness, absenteeism, and physical fitness scores were assessed. While baseline daily accrued step-counts were similar ( p = NS), SBPI significantly increased daily accrued step-counts versus control ( p < 0.05). During the study interval, academic performance increased in both groups, while SBPI had reduced tardiness ( p < 0.05) and a tendency for reduced absenteeism ( p = 0.06) postintervention. Shuttle and mile run performance decreased from pre- to postintervention in both groups. These data suggest that SBPI can increase physical activity levels and decrease tardiness in middle school students, without translating into short-term improvements in academic or physical fitness performance.
The homogenization method of roughness analysis in turbulent lubrication
Authors: Lahmar Mustapha , Bou-Saïd Benyebka , Tichy John
Published: April 2013

The hydrodynamic lubrication theory founded by Osborne Reynolds in 1886 is based on several assumptions, including that the contact surfaces are perfectly smooth, and the lubricant flow regime is laminar. However, in certain special cases these hypotheses may not be valid, and it is seen that surface roughness and turbulence affect bearing performance. The approach adopted in the present work is based on the application of the homogenization method to the turbulent Reynolds equation. In homogenization, multiscale expansion of the fluid pressure terms leads to a system of four partial differential equations governing two types of problems (local and global). The solutions are, respectively, periodic functions, and the homogenized pressure. As an illustrative example, a journal bearing with a rough surface operating in the turbulent regime is analyzed. Numerical simulations are performed by imposing periodic isotropic roughness patterns over the stationary outer cylinder surface. The homogenized solutions are compared to direct solutions of the deterministic problem. Homogenization is shown to be a powerful but practical method to attack problems of rough surfaces and is applied to turbulent lubrication for the first time. In the plain journal bearing example, the effect of roughness is to increase the load significantly in many cases. The effect of turbulence is to greatly increase the load, in both the rough and smooth cases.
Application of the fluid–structure interaction technique for the analysis of hydrodynamic lubrication problems
Authors: Wodtke Michał , Olszewski Artur , Wasilczuk Michał
Published: April 2013

Fluid–structure interaction technique seems to be one of the most promising possibilities for theoretical analysis of lubrication problems. It allows coupling of different physical fields in one computational task, taking into account the interaction between them. In this article, two sets of fluid–structure interaction analyses focusing on the bearing performance evaluation are presented. One analysis was applied to a water-lubricated journal bearing and the other to a hydrodynamic thrust bearing lubricated with oil. Steady-state operation was considered in both cases. In the presented cases of fluid–structure interaction analyses, all important phenomena accompanying bearing operation are considered, e.g. lubricant flow, structure movements and their deformations as well as heat transfer in case of thrust bearing. The problems encountered during modelling are discussed in this article, as well as the results of calculations: hydrodynamic pressures, gap geometries or temperature profiles.
Effects of municipality factors on care transitions
Authors: Aaltonen Mari , Forma Leena , Rissanen Pekka , Raitanen Jani , Jylhä Marja
Published: April 2013

Aims: To analyse whether transitions between care settings differ between municipalities in the last 2 years of life among older people in Finland. Methods: Data were derived from Finnish national registers, and include all those who died in 2002 and 2003 at the age of 70 or older except those living in very small municipalities ( n=67,027). Data include admissions and discharges from health and social care facilities (university hospitals, general hospitals, health centres, residential care facilities) and time spent outside care facilities for 730 days prior to death. Three-level negative binomial regression analyses were performed to study the effect of municipal factors on (1) the total number of all care transitions, (2) the number of transitions between home and different care facilities, and (3) transitions between different care facilities. Results: The municipality of residence had only a minor effect on the total number of care transitions, but greater variation between municipalities was found when different types of care transition were examined separately. Largest differences were found in care transitions involving specialised care. Age structure, urbanity, and economic situation of the municipality had an impact on several different care transitions. Conclusion: The total number of care transitions in 2 final years of life was approximately similar irrespective of the municipality of residence, but the findings imply differences in transitioning specialised care. Potentially, this may suggest inequality between the municipalities, but more detailed studies are needed to confirm the factors underlying these differences.
Grazing contact researches for a spindle-ball bearing system
Authors: Gao S-H , Nong S-L , Meng G , Xu W-B
Published: April 2013

This article combines the three-order harmonic balance method and eight-order Taylor expansion technique to give the qualitative analysis of responses for the spindle-ball bearing system. The effects of the bearing clearance and initial position of rotor on the frequency–response curves are investigated. As the number of contact balls alters due to the combining actions of the bearing clearance and initial position of rotor, the grazing phenomenon occurs and the frequency–response curve undergoes a major change. The system’s characteristic coefficients are also found to sharply grow at the point the number of contact balls alters. They therefore can be treated as the signs to indicate the occurrence of the grazing phenomenon, which is helpful for the researchers to study the non-linear and non-smooth properties of the spindle-ball bearing system.
Activation of indoleamine 2,3-dioxygenase by LPS in a porcine model
Authors: Wirthgen Elisa , Tuchscherer Margret , Otten Winfried , Domanska Grazyna , Wollenhaupt Karin , Tuchscherer Armin , Kanitz Ellen
Published: April 2013

Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme for the degradation of tryptophan (Trp) along the kynurenine (Kyn) pathway, and its increased activation is associated with immunologic disorders. Because the specific role of IDO activation is not yet completely clear, the aim of the present study was to establish a pig model of IDO activation for further research. The activation of IDO in pigs was induced experimentally by LPS stimulation in vivo and ex vivo. IDO activation was characterized by measuring Trp, Trp metabolites and IDO protein expression in blood, liver, lung, muscle and different brain areas. The results show that the in vivo LPS administration induced increased plasma concentrations of TNF-α and IL-10, a depletion of Trp and an increase of Kyn, indicating an elevated enzymatic activity of IDO. This was supported by an LPS-induced IDO protein expression in blood, liver and lung. The ex vivo LPS stimulation also resulted in increased TNF-α concentrations and an IDO activation, characterized by an increase of Trp metabolites and IDO protein expression. In conclusion, our data emphasize that the LPS stimulation is a suitable model for IDO activation in the domestic pig, which provides a basis for further research on immunoregulatory IDO functions.
Body mass index is not associated with cytokine induction during experimental human endotoxemia
Authors: van Eijk Lucas T , van der Pluijm Rob W , Ramakers Bart PC , Dorresteijn Mirrin J , van der Hoeven Johannes G , Kox Matthijs , Pickkers Peter
Published: April 2013

A higher body mass index (BMI) appears to be associated with lower mortality in critically ill patients, possibly explained by an altered innate immune response. However, the precise relationship between BMI and the innate immune response in humans in vivo is unknown. We investigated the relationship between BMI and the systemic cytokine response during experimental human endotoxemia. Endotoxemia was induced in 112 healthy male volunteers by intravenous administration of 2 ng/kg Escherichia coli endotoxin. Plasma concentrations of TNF-α, IL-6, IL-10 and IL-1RA were serially determined. The relationship between BMI and the cytokine response, as well as body temperature, was investigated. The BMIs of the participants ranged from 18.3 to 33.6 kg/m2, (median: 22.7 kg/m2). All participants showed a marked increase in plasma cytokine levels [median (interquartile range)] peak levels: TNF-α 509 (353–673) pg/ml; IL-6 757 (522–1098) pg/ml; IL-10 271 (159–401) pg/ml; IL-1RA 4882 (3927–6025) pg/ml; and an increase in body temperature [1.8(1.4–2.2)℃] during endotoxemia. No significant correlations were found between BMI and levels of any of the cytokines or body temperature. No relationship between BMI and the cytokine response was found in healthy volunteers subjected to experimental endotoxemia. These data question the relationship between BMI and cytokine responses in critical illness.
Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6
Authors: Witzens-Harig Mathias , Hose Dirk , Jünger Simone , Pfirschke Christina , Khandelwal Nisit , Umansky Ludmila , Seckinger Anja , Conrad Heinke , Brackertz Bettina , Rème Thierry , Gueckel Brigitte , Meißner Tobias , Hundemer Michael , Ho Anthony D. , Rossi Jean-Francois , Neben Kai , Bernhard Helga , Goldschmidt Hartmut , Klein Bernard , Beckhove Philipp
Published: April 2013

Key Points

Multiple myeloma cells inhibit myeloma-specific T cells through expression of carcinoembryonic antigen-related cell adhesion molecule-6.
Risk factors for MDS and acute leukemia following total therapy 2 and 3 for multiple myeloma
Authors: Usmani Saad Z. , Sawyer Jeffrey , Rosenthal Adam , Cottler-Fox Michele , Epstein Joshua , Yaccoby Shmuel , Sexton Rachael , Hoering Antje , Singh Zeba , Heuck Christoph J. , Waheed Sarah , Chauhan Nabeel , Johann Donald , Abdallah Al-Ola , Muzaffar Jameel , Petty Nathan , Bailey Clyde , Crowley John , van Rhee Frits , Barlogie Bart
Published: April 2013

Key Points

MDS-CAs were observed in 11% of 1080 patients and often preceded clinical MDS/acute leukemia. Risk factors for MDS-type cytogenetic abnormalities included immuno-modulatory drugs, older age, male gender, and low CD34 dose (<5 million/kg) given with first transplant.
Characterization of proposed human B-1 cells reveals pre-plasmablast phenotype
Authors: Covens Kris , Verbinnen Bert , Geukens Nick , Meyts Isabelle , Schuit Frans , Van Lommel Leentje , Jacquemin Marc , Bossuyt Xavier
Published: April 2013

Key Points

Human CD20+CD27+CD43+CD70−CD69− B cells have been described as the human counterpart of murine B-1 B cells, but this is controversial. Our data demonstrate a pre-plasmablast but not a B-1 phenotype for this population of cells.
Genomic deletion of CNGB3 is identical by descent in multiple canine breeds and causes achromatopsia
Authors: Yeh Connie Y , Goldstein Orly , Kukekova Anna V , Holley Debbie , Knollinger Amy M , Huson Heather J , Pearce-Kelling Susan E , Acland Gregory M , Komáromy András M
Published: April 2013

Background

Achromatopsia is an autosomal recessive disease characterized by the loss of cone photoreceptor function that results in day-blindness, total colorblindness, and decreased central visual acuity. The most common causes for the disease are mutations in the CNGB3 gene, coding for the beta subunit of the cyclic nucleotide-gated channels in cones. CNGB3-achromatopsia, or cone degeneration (cd), is also known to occur in two canine breeds, the Alaskan malamute (AM) and the German shorthaired pointer.

Results

Here we report an in-depth characterization of the achromatopsia phenotype in a new canine breed, the miniature Australian shepherd (MAS). Genotyping revealed that the dog was homozygous for a complete genomic deletion of the CNGB3 gene, as has been previously observed in the AM. Identical breakpoints on chromosome 29 were identified in both the affected AM and MAS with a resulting deletion of 404,820 bp. Pooled DNA samples of unrelated purebred Australian shepherd, MAS, Siberian husky, Samoyed and Alaskan sled dogs were screened for the presence of the affected allele; one Siberian husky and three Alaskan sled dogs were identified as carriers. The affected chromosomes from the AM, MAS, and Siberian husky were genotyped for 147 SNPs in a 3.93 Mb interval within the cd locus. An identical shared affected haplotype, 0.5 Mb long, was observed in all three breeds and defined the minimal linkage disequilibrium (LD) across breeds. This supports the idea that the mutated allele was identical by descent (IBD).

Conclusion

We report the occurrence of CNGB3-achromatopsia in a new canine breed, the MAS. The CNGB3-deletion allele previously described in the AM was also observed in a homozygous state in the affected MAS, as well as in a heterozygous carrier state in a Siberian husky and Alaskan sled dogs. All affected alleles were shown to be IBD, strongly suggesting an affected founder effect. Since the MAS is not known to be genetically related to the AM, other breeds may potentially carry the same cd-allele and be affected by achromatopsia.
The association between serious upper gastrointestinal bleeding and incident bisphosphonate use: a population-based nested cohort study
Authors: Knopp-Sihota Jennifer A , Cummings Greta G , Homik Joanne , Voaklander Don
Published: April 2013

Background

Oral bisphosphonates are commonly used to prevent / treat osteoporosis. However, bisphosphonate treatment is not without risk and serious adverse effects, including upper gastrointestinal bleeding (UGIB) have been described. We sought to determine if new users of bisphosphonate drugs were more likely to suffer a serious UGIB within 120 days of drug initiation.

Methods

This was a population-based nested cohort study utilizing administrative healthcare data in British Columbia, Canada. Community based individuals ≥ 65 years with a new prescription for a bisphosphonate between 1991 and 2007 were included. A multivariate logistic regression model was used to examine the relationship between older age and the development of a serious UGIB within 120 days of new exposure to oral bisphosphonate drugs.

Results

Within the exposure cohort (n = 26,223), 117 individuals had suffered a serious UGIB within 120 days of incident bisphosphonate use. Cases tended to be > 80 years old, and were significantly more likely to have had a past history of gastric ulcer disease, a remote history of serious UGIB, and had been dispensed proton pump inhibitor (PPI) medications (p < 0.001 for all comparisons). After adjustment for confounding covariates, those > 80 years were more than twice as likely to suffer a UGIB when compared to those ≤ 80 years (adjusted OR = 2.03; 95% CI 1.40–2.94). A past history of serious UGIB was the strongest predictor of UGIB within 120 days of incident bisphosphonate use (adjusted OR = 2.28; 95% CI = 1.29–4.03) followed by PPI use (adjusted OR = 2.04; 95% CI = 1.35–3.07). Males were 70% more likely to suffer an UGIB compared to females (adjusted OR = 1.69; 95% CI = 1.05–2.72).

Conclusions

Upper GIB is a rare, but serious, side effect of bisphosphonate therapy more often afflicting older individuals. At the same time, concern about potential rare adverse events should not discourage clinicians from prescribing bisphosphonate drugs, particularly in older patients who have already sustained a fragility fracture. Clinicians must remain cognizant of potential adverse events associated with bisphosphonate use and should routinely ask about pre-existing GI disorders and concurrent medication history prior to prescribing these drugs.
Quantitative threefold allele-specific PCR (QuanTAS-PCR) for highly sensitive JAK2V617F mutant allele detection
Authors: Zapparoli Giada V , Jorissen Robert N , Hewitt Chelsee A , McBean Michelle , Westerman David A , Dobrovic Alexander
Published: April 2013

Background

The JAK2 V617F mutation is the most frequent somatic change in myeloproliferative neoplasms, making it an important tumour-specific marker for diagnostic purposes and for the detection of minimal residual disease. Sensitive quantitative assays are required for both applications, particularly for the monitoring of minimal residual disease, which requires not only high sensitivity but also very high specificity.

Methods

We developed a highly sensitive probe-free quantitative mutant-allele detection method, Quantitative Threefold Allele-Specific PCR (QuanTAS-PCR), that is performed in a closed-tube system, thus eliminating the manipulation of PCR products. QuantTAS-PCR uses a threefold approach to ensure allele-specific amplification of the mutant sequence: (i) a mutant allele-specific primer, (ii) a 3′dideoxy blocker to suppress false-positive amplification from the wild-type template and (iii) a PCR specificity enhancer, also to suppress false-positive amplification from the wild-type template. Mutant alleles were quantified relative to exon 9 of JAK2.

Results

We showed that the addition of the 3′dideoxy blocker suppressed but did not eliminate false-positive amplification from the wild-type template. However, the addition of the PCR specificity enhancer near eliminated false-positive amplification from the wild-type allele. Further discrimination between true and false positives was enabled by using the quantification cycle (Cq) value of a single mutant template as a cut-off point, thus enabling robust distinction between true and false positives. As 10,000 JAK2 templates were used per replicate, the assay had a sensitivity of 1/10-4 per replicate. Greater sensitivity could be reached by increasing the number of replicates analysed. Variation in replicates when low mutant-allele templates were present necessitated the use of a statistics-based approach to estimate the load of mutant JAK2 copies. QuanTAS-PCR showed comparable quantitative results when validated against a commercial assay.

Conclusions

QuanTAS-PCR is a simple, cost-efficient, closed-tube method for JAK2 V617F mutation quantification that can detect very low levels of the mutant allele, thus enabling analysis of minimal residual disease. The approach can be extended to the detection of other recurrent single nucleotide somatic changes in cancer.
Discrimination in relation to parenthood reported by community psychiatric service users in the UK: a framework analysis
Authors: Jeffery Debra , Clement Sarah , Corker Elizabeth , Howard Louise M , Murray Joanna , Thornicroft Graham
Published: April 2013

Background

Experienced discrimination refers to an individual’s perception that they have been treated unfairly due to an attribute and is an important recent focus within stigma research. A significant proportion of mental health service users report experiencing mental illness-based discrimination in relation to parenthood. Existing studies in this area have not gone beyond prevalence, therefore little is known about the nature of experienced discrimination in relation to parenthood, and how is it constituted. This study aims to generate a typology of community psychiatric service users’ reports of mental illness-based discrimination in relation to becoming or being a parent. A secondary aim is to assess the prevalence of these types of experienced discrimination.

Methods

In a telephone survey 2026 community psychiatric service users in ten UK Mental Health service provider organisations (Trusts) were asked about discrimination experienced in the previous 12 months using the Discrimination and Stigma Scale (DISC). The sample were asked if, due to their mental health problem, they had been treated unfairly in starting a family, or in their role as a parent, and gave examples of this. Prevalence is reported and the examples of experienced discrimination in relation to parenthood were analysed using the framework method of qualitative analysis.

Results

Three hundred and four participants (73% female) reported experienced discrimination, with prevalences of 22.5% and 28.3% for starting a family and for the parenting role respectively. Participants gave 89 examples of discrimination about starting a family and 228 about parenting, and these occurred in social and professional contexts. Ten themes were identified. These related to being seen as an unfit parent; people not being understanding; being stopped from having children; not being allowed to see their children; not getting the support needed; children being affected; children avoiding their parents; children’s difficulties being blamed on the parent’s mental health problem; not being listened to; and being undermined as a parent.

Conclusions

This research highlights the need for: greater support for parents with mental illness, those wishing to have children, and those who lose access or custody; services to better meet the needs of children with a mentally ill parent; training about discrimination for professionals; and parenting issues to be included in anti-stigma programmes.
Multicore-based 3D-DWT video encoder
Authors: Galiano Vicente , López-Granado Otoniel , Malumbres Manuel P. , Migallón Hector
Published: April 2013

Three-dimensional wavelet transform (3D-DWT) encoders are good candidates for applications like professional video editing, video surveillance, multi-spectral satellite imaging, etc. where a frame must be reconstructed as quickly as possible. In this paper, we present a new 3D-DWT video encoder based on a fast run-length coding engine. Furthermore, we present several multicore optimizations to speed-up the 3D-DWT computation. An exhaustive evaluation of the proposed encoder (3D-GOP-RL) has been performed, and we have compared the evaluation results with other video encoders in terms of rate/distortion (R/D), coding/decoding delay, and memory consumption. Results show that the proposed encoder obtains good R/D results for high-resolution video sequences with nearly in-place computation using only the memory needed to store a group of pictures. After applying the multicore optimization strategies over the 3D DWT, the proposed encoder is able to compress a full high-definition video sequence in real-time.
Mathematical models for the Notch and Wnt signaling pathways and the crosstalk between them during somitogenesis
Authors: Wang Hong-yan , Huang Yan-xin , Qi Yun-feng , Zhang Yu , Bao Yong-li , Sun Lu-guo , Zheng Li-hua , Zhang Yu-wei , Ma Zhi-qiang , Li Yu-xin
Published: April 2013

Background

Somitogenesis is a fundamental characteristic feature of development in various animal embryos. Molecular evidence has proved that the Notch and Wnt pathways play important roles in regulating the process of somitogenesis and there is crosstalk between these two pathways. However, it is difficult to investigate the detailed mechanism of these two pathways and their interactions in somitogenesis through biological experiments. In recent years some mathematical models have been proposed for the purpose of studying the dynamics of the Notch and Wnt pathways in somitogenesis. Unfortunately, only a few of these models have explored the interactions between them.

Results

In this study, we have proposed three mathematical models for the Notch signalling pathway alone, the Wnt signalling pathway alone, and the interactions between them. These models can simulate the dynamics of the Notch and Wnt pathways in somitogenesis, and are capable of reproducing the observations derived from wet experiments. They were used to investigate the molecular mechanisms of the Notch and Wnt pathways and their crosstalk in somitogenesis through the model simulations.

Conclusions

Three mathematical models are proposed for the Notch and Wnt pathways and their interaction during somitogenesis. The simulations demonstrate that the extracellular Notch and Wnt signals are essential for the oscillating expressions of both Notch and Wnt target genes. Moreover, the internal negative feedback loops and the three levels of crosstalk between these pathways play important but distinct roles in maintaining the system oscillation. In addition, the results of the parameter sensitivity analysis of the models indicate that the Notch pathway is more sensitive to perturbation in somitogenesis.
A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations
Authors: Roche Michael , Salimi Hamid , Duncan Renee , Wilkinson Brendan L , Chikere Kelechi , Moore Miranda S , Webb Nicholas E , Zappi Helena , Sterjovski Jasminka , Flynn Jacqueline K , Ellett Anne , Gray Lachlan R , Lee Benhur , Jubb Becky , Westby Mike , Ramsland Paul A , Lewin Sharon R , Payne Richard J , Churchill Melissa J , Gorry Paul R
Published: April 2013

Background

The CCR5 antagonist maraviroc (MVC) inhibits human immunodeficiency virus type 1 (HIV-1) entry by altering the CCR5 extracellular loops (ECL), such that the gp120 envelope glycoproteins (Env) no longer recognize CCR5. The mechanisms of HIV-1 resistance to MVC, the only CCR5 antagonist licensed for clinical use are poorly understood, with insights into MVC resistance almost exclusively limited to knowledge obtained from in vitro studies or from studies of resistance to other CCR5 antagonists. To more precisely understand mechanisms of resistance to MVC in vivo, we characterized Envs isolated from 2 subjects who experienced virologic failure on MVC.

Results

Envs were cloned from subjects 17 and 24 before commencement of MVC (17-Sens and 24-Sens) and after virologic failure (17-Res and 24-Res). The Envs cloned during virologic failure showed broad divergence in resistance levels, with 17-Res Env exhibiting a relatively high maximal percent inhibition (MPI) of ~90% in NP2-CD4/CCR5 cells and peripheral blood mononuclear cells (PBMC), and 24-Res Env exhibiting a very low MPI of ~0 to 12% in both cell types, indicating relatively “weak” and “strong” resistance, respectively. Resistance mutations were strain-specific and mapped to the gp120 V3 loop. Affinity profiling by the 293-Affinofile assay and mathematical modeling using VERSA (Viral Entry Receptor Sensitivity Analysis) metrics revealed that 17-Res and 24-Res Envs engaged MVC-bound CCR5 inefficiently or very efficiently, respectively. Despite highly divergent phenotypes, and a lack of common gp120 resistance mutations, both resistant Envs exhibited an almost superimposable pattern of dramatically increased reliance on sulfated tyrosine residues in the CCR5 N-terminus, and on histidine residues in the CCR5 ECLs. This altered mechanism of CCR5 engagement rendered both the resistant Envs susceptible to neutralization by a sulfated peptide fragment of the CCR5 N-terminus.

Conclusions

Clinical resistance to MVC may involve divergent Env phenotypes and different genetic alterations in gp120, but the molecular mechanism of resistance of the Envs studied here appears to be related. The increased reliance on sulfated CCR5 N-terminus residues suggests a new avenue to block HIV-1 entry by CCR5 N-terminus sulfopeptidomimetic drugs.
LocARNAscan: Incorporating thermodynamic stability in sequence and structure-based RNA homology search
Authors: Will Sebastian , Siebauer Michael F , Heyne Steffen , Engelhardt Jan , Stadler Peter F , Reiche Kristin , Backofen Rolf
Published: April 2013

Background

The search for distant homologs has become an import issue in genome annotation. A particular difficulty is posed by divergent homologs that have lost recognizable sequence similarity. This same problem also arises in the recognition of novel members of large classes of RNAs such as snoRNAs or microRNAs that consist of families unrelated by common descent. Current homology search tools for structured RNAs are either based entirely on sequence similarity (such as or ) or combine sequence and secondary structure. The most prominent example of the latter class of tools is . Alternatives are descriptor-based methods. In most practical applications published to-date, however, the information contained in covariance models or manually prescribed search patterns is dominated by sequence information. Here we ask two related questions: (1) Is secondary structure alone informative for homology search and the detection of novel members of RNA classes? (2) To what extent is the thermodynamic propensity of the target sequence to fold into the correct secondary structure helpful for this task?

Results

Sequence-structure alignment can be used as an alternative search strategy. In this scenario, the query consists of a base pairing probability matrix, which can be derived either from a single sequence or from a multiple alignment representing a set of known representatives. Sequence information can be optionally added to the query. The target sequence is pre-processed to obtain local base pairing probabilities. As a search engine we devised a semi-global scanning variant of ’s algorithm for sequence-structure alignment. The tool is optimized for speed and low memory consumption. In benchmarking experiments on artificial data we observe that the inclusion of thermodynamic stability is helpful, albeit only in a regime of extremely low sequence information in the query. We observe, furthermore, that the sensitivity is bounded in particular by the limited accuracy of the predicted local structures of the target sequence.

Conclusions

Although we demonstrate that a purely structure-based homology search is feasible in principle, it is unlikely to outperform tools such as in most application scenarios, where a substantial amount of sequence information is typically available. The approach will profit, however, from high throughput methods to determine RNA secondary structure. In transcriptome-wide applications, such methods will provide accurate structure annotations on the target side.

Availability

Source code of the free software 1.0 and supplementary data are available athttp://www.bioinf.uni-leipzig.de/Software/LocARNAscan.