bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Multiple Task Activation and Reproducibility in Patients with Benign and Low-grade Neoplasms
Authors: McKinsey R. D. , Moritz C. H. , Meyerand M. E. , Tomé W. A.
Published: October 2014

Twenty-four patients with proven benign and low-grade brain neoplasms each performed two iterations of four fMRI paradigms: language (word generation), primary and association auditory (text listening), upper limb fine motor control (alternating-limb bilateral finger tapping), and primary visual perception (reversing checkerboard). Activation clusters with varying thresholds were generated for each scan and used to calculate reproducibility parameters: Difference in the Center of Mass (COM) location, Rsize, and Roverlap. The average difference in the COM, Rsize, and Roverlap values ranged from 1.70 ± 0.53 mm −10.60 ± 3.21 mm, 0.6 ± 0.04–0.90 ± 0.05 and 0.23 ± 0.12 −1 ± 0.16 respectively for all tasks. These values are within the range of, or higher than, previously published reports on fMRI test-retest precision. FMRI is indicated to be a noninvasive tool with acceptable reproducibility measures for assessing the localizations of multiple language and sensorimotor functions in patients scheduled for radiotherapy treatment.
Influence of iMRI-Guidance on the Extent of Resection and Survival of Patients with Glioblastoma Multiforme
Authors: Senft Christian , Franz Kea , Blasel Stella , Oszvald Ági , Rathert Julian , Seifert Volker , Gasser Thomas
Published: October 2014

Intraoperative MRI (iMRI) is used in glioma surgery mainly to determine the extent of resection, allowing surgeons to immediately continue resection in case of residual tumor tissue. The aim of this study is to report on the influence of the use of iMRI on the extent of resection and survival of patients with glioblastoma multiforme (GBM).

We analyzed our prospectively collected database of patients with GBM operated upon during the initial period after installation of an iMRI; between July 2004 and December 2005, all patients with GBM undergoing intended complete tumor resection were included in this study, while patients undergoing mere tumor biopsy or intended incomplete resection were not.

In total, 43 Patients met the inclusion criteria. Of these, 10 patients (23.3%) were operated upon with the help of iMRI while 33 underwent conventional tumor resection. All patients underwent postoperative high-field MR imaging at 1.5 Tesla to determine the extent of resection. Subsequently, all patients received adjuvant treatment. Median patient age was 60.0 years; median overall survival was 70.7 weeks. Radiologically complete tumor resection (P < 0.001) and the administration of temozolomide chemotherapy (P < 0.01) were statistically significant prognostic factors in a multivariate analysis. The rate of complete tumor resections was significantly higher in the iMRI group than in the conventional surgery group (P < 0.05). Patient age was not a prognostic factor in our series of patients (P = 0.22). Intraoperative MRI is a helpful tool to increase the extent of resection in GBM surgery and thereby improve patient survival.
CyberKnife Radiosurgery for Prostate Cancer
Authors: Katz Alan J.
Published: October 2014

Treatment of prostate cancer with SBRT is an area of significant controversy for many in the radiation oncology community despite radiobiologic data that strongly suggest the prostate would be an excellent SBRT target. Recently, new data have emerged that show promising outcomes with minimal toxicity for CyberKnife SBRT of prostate cancer. In the following we present the motivating factors for prostate cancer SBRT followed by a critical evaluation of the current literature and discussion of the future of prostate cancer treatment with SBRT.
Hypofractionated Extracranial Stereotactic Radiotherapy Boost for Gynecologic Tumors: A Promising Alternative to High-Dose Rate Brachytherapy
Authors: Jorcano Sandra , Mollà Meritxell , Escudé Lluís , Sanz Sergi , Hidalgo Alberto , Toscas Jose Ignacio , Linero Dolors , Miralbell Raymond
Published: October 2014

The purpose of this study is to report toxicity and outcome results in patients with gynaecological tumours treated with a final boost using extra-cranial stereotactic radiotherapy (SRT) with a linac-based micro-multileaf collimator technique as an alternative to high-dose rate brachytherapy (HDR-BT). Since January 2002, 26 patients with either endometrial (n = 17) or cervical (n = 9) cancer were treated according to this protocol: 45–50.4 Gy external radiotherapy (RT) to the pelvic ± para-aortic regions followed by a final SRT boost of 2 × 7 Gy to the vaginal vault (4–7 day interval between fractions). Median age was 62 years (37–74 range). Fifteen patients were diagnosed with adenocarcinoma, 7 with squamous-cell carcinoma, and 4 with sarcoma. FIGO stage I (n = 17), stage II (n = 7), and stage III (n = 2). Toxicity was scored according to RTOG/EORTC criteria.

No severe (>grade-3) acute urinary or low-gastrointestinal (GI) toxicity was observed during treatment and up to 3 months after treatment completion. Moderate (grade ≤ 3) acute urinary or low-GI toxicity was observed in 23% and 35% of patients, respectively. After a median follow-up of 47 months (4–77, range), late urinary, low-GI, and sexual ≥grade-2 (worst score) has been reported in 4%, 12% and 29.4% of patients, respectively. The 3-year loco-regional failure-free and overall survival rates were 96% and 95%, respectively. Preliminary results on feasibility, tolerance, and outcome with SRT are encouraging and may be considered a sound alternative to HDR-BT for gynecologic tumors.
Sensitivity Study to Evaluate the Dosimetric Impact of Off-Axis Ratio Profiles Misalignment on TomoTherapy Second Dose Validation
Authors: He Weihong , Vazquez Q Luis A , Shi Chengyu , Papanikolaou Nikos
Published: October 2014

Accurate dose planning and delivery are very important in the intensity modulated radiation therapy. For helical TomoTherapy dose validation, a TomoTherapy second check software, called MU-Tomo, has been developed using archived patient documents, initial coordinates and planned dose of the point of calculation, and common dosimetric functions. Based on this software, sensitivity studies on 50 patient cases have been evaluated to show the impact of off-axis ratio profile misalignment on point dose calculation. Off-axis ratio is defined as the dose profile normalized to its maximum dose value. Sensitivity studies were done for three scenarios: oscillating the fluctuation regions of two off-axis profiles, shifting the profiles, and rotating the profiles. The result of the oscillation trial is linear along the change of longitudinal off-axis ratio (OARy), while oscillating the lateral off-axis ratio (OARx) has little influence on the dose calculation. For shifting, the variation in the percentage difference from the non-shifting value is about 15 times larger in OARy modification than in OARx modification. Rotating OARx by ±6° gave less than 1.5% ± 0.20% difference compared to the non-rotating value. Rotating OARy by ±1° changes the result more than 5% ± 2.69%. Therefore, for helical TomoTherapy dose validation, commissioned OARy profiles are more sensitive than OARx to oscillation, shifting and rotating. As a result, different tolerances for OARx and OARy may be required for annual quality assurance.
Stereotactic Body Radiotherapy as Boost for Organ-confined Prostate Cancer
Authors: Katz Alan J. , Santoro Michael , Ashley Richard , Diblasio Ferdinand , Witten Matthew
Published: October 2014

Stereotactic body radiotherapy (SBRT) boost following external beam radiation therapy (EBRT) for advanced localized prostate cancer may reduce toxicity while escalating the dose. We present preliminary biochemical control and urinary, rectal and sexual toxicities for 73 patients treated with SBRT as a boost to EBRT. Forty-one intermediate- and 32 high-risk localized prostate cancer patients received 45 Gy EBRT with SBRT boost. Twenty-eight patients (38.3%) received a total SBRT boost dose of 18 Gy (3 fractions of 6 Gy), 28 patients (38.3%) received 19.5 Gy (3 fractions of 6.5 Gy), and 17 patients (23.2%) received 21 Gy (3 fractions of 7 Gy). Toxicity was assessed using the Radiation Therapy Oncology Group urinary and rectal toxicity scale. Biochemical failure was assessed using the Phoenix definition. The median follow-up was 33 months (range, 22 − 43 months). Less than 7% Grade II and no higher grade acute toxicities occurred. To date, one Grade III and no Grade IV late toxicities occurred. For the 97% of patients with 24 months minimum follow-up, 71.8% achieved a PSA nadir threshold of 0.5 ng/mL. Three intermediate-risk and seven high-risk biochemical failures occurred; one high-risk patient died of his cancer. Three-year actuarial biochemical control rates were 89.5% and 77.7% for intermediate- and high-risk patients, respectively. SBRT boost for prostate cancer treatment is safe and feasible with minimal acute toxicity. At 33 months late toxicity and biochemical control are promising. Long-term durability of these findings remains to be established.
CyberKnife Stereotactic Ablative Radiotherapy for Lung Tumors
Authors: Gibbs Iris C. , Loo Billy W.
Published: October 2014

Stereotactic ablative radiotherapy (SABR) has emerged as a promising treatment for early stage non-small cell lung cancer, particularly for patients unable to tolerate surgical resection. High rates of local tumor control have been demonstrated with acceptable toxicity and the practical advantage of a short course of treatment. The CyberKnife image-guided robotic radiosurgery system has unique technical characteristics that make it well suited for SABR of tumors that move with breathing, including lung tumors. We review the qualities of the CyberKnife platform for lung tumor SABR, and provide a summary of clinical data using this system specifically.
Toward Truly Optimal IMRT Dose Distribution: Inverse Planning with Voxel-specific Penalty
Authors: Lougovski Pavel , LeNoach Jordan , Zhu Lei , Ma Yunzhi , Censor Yair , Xing Lei
Published: October 2014

Purpose:

To establish an inverse planning framework with adjustable voxel penalty for more conformal IMRT dose distribution as well as improved interactive controllability over the regional dose distribution of the resultant plan.

Materials and Method:

In the proposed coarse-to-fine planning scheme, a conventional inverse planning with organ specific parameters is first performed. The voxel penalty scheme is then “switched on” by allowing the prescription dose to change on an individual voxel scale according to the deviation of the actual voxel dose from the ideally desired dose. The rationale here is intuitive: when the dose at a voxel does not meet its ideal dose, it simply implies that this voxel is not competitive enough when compared with the ones that have met their planning goal. In this case, increasing the penalty of the voxel by varying the prescription can boost its competitiveness and thus improve its dose. After the prescription adjustment, the plan is re-optimized. The dose adjustment/re-optimization procedure is repeated until the resultant dose distribution cannot be improved anymore. The prescription adjustment on a finer scale can be accomplished either automatically or manually. In the latter case, the regions/voxels where a dose improvement is needed are selected visually, unlike in the automatic case where the selection is done purely based on the difference of the actual dose at a given voxel and its ideal prescription. The performance of the proposed method is evaluated using a head and neck and a prostate case.

Results:

An inverse planning framework with the voxel-specific penalty is established. By adjusting voxel prescriptions iteratively to boost the region where large mismatch between the actual calculated and desired doses occurs, substantial improvements can be achieved in the final dose distribution. The proposed method is applied to a head and neck case and a prostate case. For the former case, a significant reduction in the maximum dose to the brainstem is achieved while the PTV dose coverage is greatly improved. The doses to other organs at risk are also reduced, ranging from 10% to 30%. For the prostate case, the use of the voxel penalty scheme also results in vast improvements to the final dose distribution. The PTV experiences improved dose uniformity and the mean dose to the rectum and bladder is reduced by as much as 15%.

Conclusion:

Introduction of the spatially non-uniform and adjustable prescription provides room for further improvements of currently achievable dose distributions and equips the planner with an effective tool to modify IMRT dose distributions interactively. The technique is easily implementable in any existing inverse planning platform, which should facilitate clinical IMRT planning process and, in future, off-line/on-line adaptive IMRT.
Near Infrared Photonic Finger Imager for Prostate Cancer Screening
Authors: Pu Y. , Wang W. B. , Xu M. , Tang G. C. , Budansky Y. , Sharanov M. , Achilefu S. , Eastham J. A. , Alfano R. R.
Published: October 2014

A portable rectal near infrared (NIR) scanning polarization imaging unit with an optical fiber-based rectal probe, designated as a Photonic Finger (PF), was designed, developed, built and tested. PF was used to image and locate the three dimensional (3D) positions of abnormal prostate tissue embedded inside normal prostate tissue. An inverse image reconstruction algorithm, namely Optical Tomography using Independent Component Analysis (OPTICA) was developed to unmix the signal from targets (cancerous tissue) embedded in a turbid media (normal tissue) in the backscattering imaging geometry. The Photonic Finger combined with OPTICA was ex vivo tested to characterize different target(s) inside different tissue medium, including cancerous prostate tissue embedded inside large pieces of normal tissue. This new developed instrument, Photonic Finger, may provide an alternative imaging technique, which is accurate, of high spatial resolution and non-or-less invasive for prostate cancers screening.
Transrectal Ultrasound-Integrated Spectral Optical Tomography of Hypoxic Progression of a Regressing Tumor in a Canine Prostate
Authors: Jiang Z. , Piao D. , Bartels K. E. , Holyoak G. R. , Ritchey J. W. , Ownby C. L. , Rock K. , Slobodov G.
Published: October 2014

The objective of this study was to evaluate if transrectal optical tomography implemented at three wavelength bands for spectral detection could monitor changes of the hemoglobin oxygen saturation (StO2) in addition to those of the total hemoglobin concentration ([HbT]) in lesions of a canine prostate, including an induced tumor modeling canine prostate cancer. Near-infrared (NIR) optical tomography was integrated with ultrasound (US) for transrectal imaging. Multi-spectral detection at 705 nm, 785 nm and 808 nm rendered measurements of [HbT] and StO2. Canine transmissible venereal tumor (TVT) cells were injected into the right lobe of a dog's prostate gland, which had a pre-existing cyst in the left lobe. Longitudinal assessments of the prostate were performed weekly over a 63-day duration by NIR imaging concurrent with grey-scale and Doppler US. Ultrasonography revealed a bi-lobular tumor-mass regressing from day-49 to day-63. At day-49 this tumor-mass developed a hypoxic core that became larger and more intense by day-56 and expanded further by day-63. The tumor-mass presented a strong hyper-[HbT] feature on day-56 that was inconsistent with US-visualized blood flow. Histology confirmed two necrotic TVT foci within this tumor-mass. The cyst appeared to have a large anoxic-like interior that was greater in size than its ultrasonographically delineated lesion, and a weak lesional elevation of [HbT]. On day-56, the cyst presented a strong hyper-[HbT] feature consistent with US-resolved blood flow. Histology revealed acute and chronic hemorrhage in the periphery of the cyst. The NIR imaging features of two other TVT nodules and a metastatic lymph node were evaluated retrospectively. Transrectal US-integrated spectral optical tomography seems to enable longitudinal monitoring of intra-lesional oxygenation dynamics in addition to the hemoglobin content of lesions in the canine prostate.
Using In-Vivo Fluorescence Imaging in Personalized Cancer Diagnostics and Therapy, an Image and Treat Paradigm
Authors: Ardeshirpour Yasaman , Chernomordik Victor , Capala Jacek , Hassan Moinuddin , Zielinsky Rafal , Griffiths Gary , Achilefu Samuel , Smith Paul , Gandjbakhche Amir
Published: October 2014

The major goal in developing drugs targeting specific tumor receptors, such as Monoclonal AntiBodies (MAB), is to make a drug compound that targets selectively the cancer-causing biomarkers, inhibits their functionality, and/or delivers the toxin specifically to the malignant cells. Recent advances in MABs show that their efficacy depends strongly on characterization of tumor biomarkers. Therefore, one of the main tasks in cancer diagnostics and treatment is to develop non-invasive in-vivo imaging techniques for detection of cancer biomarkers and monitoring their down regulation during the treatment. Such methods can potentially result in a new imaging and treatment paradigm for cancer therapy. In this article we have reviewed fluorescence imaging approaches, including those developed in our group, to detect and monitor Human Epidermal Growth Factor 2 (HER2) receptors before and during therapy. Transition of these techniques from the bench to bedside is the ultimate goal of our project. Similar approaches can be used potentially for characterization of other cancer related cell biomarkers.
A Spatial Resolution Study of a New Optical Tomography-Based Polymer Gel Dosimetry System
Authors: Sriprisan S. I. , Lopatiuk-Tirpak O. , Meeks S. L. , Zeidan O. A.
Published: October 2014

A spatial resolution investigation of the OCTOPUS™-IQ scanner in combination with the new BANG3-Pro2® polymer gel was performed by scanning a high-contrast needle phantom. The phantom contained five thin needles (0.3 mm diameter) embedded in gel positioned in different patterns: needles were inserted (a) at 45° angle from the center of the gel container, and (b) vertically along the gel axis. The non-irradiated needle phantoms were scanned at various slice spacings (0.25–1.0 mm) and for two different laser beam orientations. Optical density profiles and their full width at half maximum (FWHM) were evaluated for resolution limit. The modulation transfer function (MTF) corresponding to measured point spread function (PSF) data was calculated. With high resolution scanning mode and 0.25 mm pixel resolution, the measured PSFs at the center of the gel dosimeter have a FWHM of 0.95 mm. The MTF for the 0.25 mm reconstruction pixel size suggests that the resolution of the system is 0.5 mm or less. We also observed a progressive degradation of the vertical needle images with off-axis distance, attributable to the defocusing of the laser beam. No significant degradation was observed up to the maximum useful reconstructed image radius of 50 mm from the gel dosimeter center axis.
Privacy in Confidential Administrative Micro Data
Authors: Hochfellner Daniela , Müller Dana , Schmucker Alexandra
Published: October 2014

The demand for comprehensive and innovative data is constantly growing in social science. In particular, micro data from various social security agencies become more and more attractive. In contrast to survey data, administrative data offer a census with highly reliable information but are restricted in their usage. To make them accessible for researchers, data or research output either have to be anonymized or released after disclosure review procedures have been used. This article discusses the trade-off between maintaining a high capability of research potential while protecting private information, by exploiting the data disclosure portfolio and the adopted disclosure strategies of the Research Data Center of the German Federal Employment Agency.
Clinical trials in crisis: Four simple methodologic fixes
Authors: Vickers Andrew J
Published: October 2014

There is growing consensus that the US clinical trials system is broken, with trial costs and complexity increasing exponentially, and many trials failing to accrue. Yet, concerns about the expense and failure rate of randomized trials are only the tip of the iceberg; perhaps what should worry us most is the number of trials that are not even considered because of projected costs and poor accrual. Several initiatives, including the Clinical Trials Transformation Initiative and the “Sensible Guidelines Group” seek to push back against current trends in clinical trials, arguing that all aspects of trials—including design, approval, conduct, monitoring, analysis, and dissemination—should be based on evidence rather than contemporary norms. Proposed here are four methodologic fixes for current clinical trials. The first two aim to simplify trials, reducing costs, and increasing patient acceptability by dramatically reducing eligibility criteria—often to the single criterion that the consenting physician is uncertain which of the two randomized arms is optimal—and by clinical integration, investment in data infrastructure to bring routinely collected data up to research grade to be used as endpoints in trials. The second two methodologic fixes aim to shed barriers to accrual, either by cluster randomization of clinicians (in the case of modifications to existing treatment) or by early consent, where patients are offered the chance of being randomly selected to be offered a novel intervention if disease progresses at a subsequent point. Such solutions may be partial, or result in a new set of problems of their own. Yet, the current crisis in clinical trials mandates innovative approaches: randomized trials have resulted in enormous benefits for patients, and we need to ensure that they continue to do so.
Principals’ perceptions about performance agreements as motivational action
Authors: Heystek Jan
Published: October 2014

Principals, as one of the professional leaders in a school, are accountable for the quality of education in the school. This is a part of the normal job description and expectations for the person in such a post. In the South African context with a large number of underperforming schools, there is an intention to have an additional performance agreement as a part of performance management, to be signed by principals to hold them accountable for the expected examination results. This article investigated the understanding of principals of the possible motivational implications if the performance agreement is implemented. It also focuses on the issue of what may motivate principals to improve their performance towards sustainable quality education. Motivational theories are used as the lens to understand the principals’ perceptions of this performance agreement process. The focus group interviews indicated that most principals are not in favour of the intended implementation and that it may rather have a negative influence on their motivation levels.
Parkinson’s disease: initial presentation
Authors: Weatherburn Christopher , Simon Chantal
Published: October 2014

In 1817, James Parkinson described a ‘shaking palsy’ that subsequently took his name. Parkinson’s disease is a chronic, progressive neurological condition that has a profound impact on a sufferer’s quality of life. It is common condition that will affect around 1 in 40 of us in our lifetimes. Early diagnosis results in treatment to reduce symptoms and preserve quality of life, but also enables planning for the future. Most patients with Parkinson’s disease will initially present to their GP. This article explains why diagnosis can be difficult and provides a guide to possible features that might trigger referral for specialist diagnosis.
High prevalence of symptoms in a severely abused “non‐patient” women population
Authors: Pallotta N , Piacentino D , Ciccantelli B , Rivera M , Golini N , Spagnoli A , Vincoli G , Farchi S , Corazziari ES
Published: October 2014

Objective

The objective of this article is to assess the prevalence of somatic symptoms and of gastrointestinal (GI) syndromes in abused “non‐patient” women and the association with the time of perpetration, type, and severity of abuse.

Methods

Sixty‐seven women, 18–58 years, receiving shelter in anti‐violence associations were invited to fill out an anonymous questionnaire with a medical and an abuse section. The severity of abuse was expressed as the 0–6 Abuse Severity Measure (ASM). The association between abuse characteristics and the number of symptoms, and GI syndromes was assessed by Poisson regression model.

Results

Most women suffered from childhood and adulthood sexual and physical abuse. They reported a mean of 5.1 GI symptoms (range 0–13; median 5; IQR 6) and of 1.3 extra‐GI symptoms (range 0–6; median 1; IQR 2); 30% of women matched the Rome II Criteria for one, 36% for two, and 4.4% for three or more syndromes, respectively. Women with an ASM of 5–6, having suffered from both sexual and physical abuse, reported significantly (p  = 0.02) more GI symptoms, but not extra‐GI ones (p  = 0.07), and met criteria for more GI syndromes than women with an ASM ≤4 and those reporting only one type of abuse. No association was found between the time of perpetration of the abuse and the number of GI and extra‐GI symptoms.

Conclusions

Symptoms in abused “non‐patient” women mainly concern the abdomen and the GI tract. A history of severe, combined physical and sexual abuse is associated with a higher number of GI symptoms.
ICD–11 Complex PTSD in U.S. National and Veteran Samples
Authors: Wolf Erika J. , Miller Mark W. , Kilpatrick Dean , Resnick Heidi S. , Badour Christal L. , Marx Brian P. , Keane Terence M. , Rosen Raymond C. , Friedman Matthew J.
Published: October 2014

The 11th edition of the International Classification of Diseases ( ICD–11) is under development, and current proposals include major changes to trauma-related psychiatric diagnoses, including a heavily restricted definition of posttraumatic stress disorder (PTSD) and the addition of complex PTSD (CPTSD). We aimed to test the postulates of CPTSD in samples of 2,695 community participants and 323 trauma-exposed military veterans. CPTSD prevalence estimates were 0.6% and 13% in the community and veteran samples, respectively; one quarter to one half of those with PTSD met criteria for CPTSD. There were no differences in trauma exposure across diagnoses. A factor mixture model with two latent dimensional variables and four latent classes provided the best fit in both samples: Classes differed by their level of symptom severity but did not differ as a function of the proposed PTSD versus CPTSD diagnoses. These findings should raise concerns about the distinctions between CPTSD and PTSD proposed for ICD–11.
How I treat polycythemia vera
Authors: Vannucchi Alessandro M.
Published: October 2014

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm associated with JAK2 mutations (V617F or exon 12) in almost all cases. The World Health Organization has defined the criteria for diagnosis, but it is still unclear which parameter (hemoglobin or hematocrit) is the most reliable for demonstrating increased red cell volume and for monitoring response to therapy; also, the role of bone marrow biopsy is being revisited. PV is associated with reduced survival because of cardiovascular complications and progression to post-PV myelofibrosis or leukemia. Criteria for risk-adapted treatment rely on the likelihood of thrombosis. Controlled trials have demonstrated that incidence of cardiovascular events is reduced by sustained control of hematocrit with phlebotomies (low-risk patients) and/or cytotoxic agents (high-risk patients) and antiplatelet therapy with aspirin. Hydroxyurea and interferon may be used as first-line treatments, whereas busulfan is reserved for patients that are refractory or resistant to first-line agents. However, there is no evidence that therapy improves survival, and the significance of reduction of JAK2 mutated allele burden produced by interferon is unknown. PV is also associated with a plethora of symptoms that are poorly controlled by conventional therapy. This article summarizes my approach to the management of PV in daily clinical practice.
Predictors of positive and negative parenting behaviours: evidence from the ALSPAC cohort
Authors: Thomson Rachel M , Allely Clare S , Purves David , Puckering Christine , McConnachie Alex , Johnson Paul CD , Golding Jean , Gillberg Christopher , Wilson Philip
Published: October 2014

Background

This study aimed to establish the predictors of positive and negative parenting behaviours in a United Kingdom population. The majority of previous research has focused on specific risk factors and has used a variety of outcome measures. This study used a single assessment of parenting behaviours and started with a wide range of potential pre- and post-natal variables; such an approach might be used to identify families who might benefit from parenting interventions.

Methods

Using a case-control subsample of 160 subjects from the Avon Longitudinal Study of Parents and Children (ALSPAC), regression analysis was undertaken to model parenting behaviours at 12 months as measured by the Mellow Parenting Observational System.

Results

Positive parenting increased with maternal age at delivery, levels of education and with prenatal anxiety. More negative interactions were observed among younger mothers, mothers with male infants, with prenatal non-smokers and among mothers who perceived they had a poor support structure.

Conclusions

This study indicates two factors which may be important in identifying families most at risk of negative parenting: younger maternal age at delivery and lack of social support during pregnancy. Such factors could be taken into account when planning provision of services such as parenting interventions. We also established that male children were significantly more likely to be negatively parented, a novel finding which may suggest an area for future research. However the findings have to be accepted cautiously and have to be replicated, as the measures used do not have established psychometric validity and reliability data.
Dietary elimination of children with food protein induced gastrointestinal allergy – micronutrient adequacy with and without a hypoallergenic formula?
Authors: Meyer Rosan , De Koker Claire , Dziubak Robert , Godwin Heather , Dominguez‐Ortega Gloria , Shah Neil
Published: October 2014

Background

The cornerstone for management of Food protein‐induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake.

Method

A prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi‐quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS).

Results

One‐hundred‐and‐five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 ‐ 67.7]. Fifty‐three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS.

Conclusion

This study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies.
A radiographic and anthropometric study of the effect of a contoured sandal and foot orthosis on supporting the medial longitudinal arch
Authors: Escalona‐Marfil Carles , McPoil Thomas G , Mellor Rebecca , Vicenzino Bill
Published: October 2014

Background

In‐shoe foot orthoses improve conditions such as plantar heel pain (fasciitis), probably due to their ability to raise the medial longitudinal arch of the foot and lower the stress on the plantar tissues. Increasingly the arch‐profile form of the in‐shoe foot orthosis is being incorporated into sandal footwear, providing an alternative footwear option for those who require an orthosis. The purpose of this study was to evaluate if a sandal that incorporates the arch‐profile of an in‐shoe foot orthosis does indeed raise the medial longitudinal arch.

Methods

Three commercially available non‐medical devices (contoured and flat sandal, prefabricated in‐shoe orthosis) worn by healthy individuals were studied in two independent experiments, one using radiographic measurements in Australia (n = 11, 6 female, age 26.1 ± 4.3 yrs, BMI 22.0 ± 2.4 kg/m2) and the other utilising anthropometric measures in the USA (n = 10, 6 female, age 26.3 ± 3.8 yrs, BMI 23.5 ± 3.7 kg/m2). A barefoot condition was also measured. Dorsal arch height was measured in both experiments, as well as in subtalar neutral in the anthropometric experiment. One way repeated measures ANOVA with follow up Bonferroni‐corrected pairwise comparisons were used to test differences between the conditions (contoured and flat sandal, orthosis, barefoot). Mean difference and 95% confidence intervals (CI) and standardised mean differences (SMD) were also calculated.

Results

The contoured sandal significantly increased dorsal arch height compared to barefoot and flat sandal in both the anthropometric and radiographic experiments with SMD ranging from 0.95 (mean difference 5.1 mm (CI: 0.3, 1.6)) to 1.8 (4.3 mm (1.9, 6.6)). There were small differences between the contoured sandal and orthosis of 1.9 mm (0.6, 3.3) in the radiographic experiment and 1.2 mm (‐0.4, 0.9) in the anthropometric experiment. The contoured sandal approximated the subtalar neutral position (0.4 mm (‐0.5, 0.7)).

Conclusions

Medial longitudinal arch height is elevated by contoured sandals and approximates subtalar joint neutral position of the foot and that achieved by an orthosis. Practitioners wanting to increase the medial longitudinal arch can do so with either an orthosis or a contoured sandal that includes the raised arch profile form of an orthosis.
Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: a microarray related study
Authors: Wan Zhong-Yuan , Song Fang , Sun Zhen , Chen Yu-Fei , Zhang Wei-Lin , Samartzis Dino , Ma Chi-Jiao , Che Lu , Liu Xu , Ali M-Azam , Wang Hai-Qiang , Luo Zhuo-Jing
Published: October 2014

Introduction

In addition to the well-known short noncoding RNAs such as microRNAs (miRNAs), increasing evidence suggests that long noncoding RNAs (lncRNAs) act as key regulators in a wide aspect of biologic processes. Dysregulated expression of lncRNAs has been demonstrated being implicated in a variety of human diseases. However, little is known regarding the role of lncRNAs with regards to intervertebral disc degeneration (IDD). In the present study we aimed to determine whether lncRNAs are differentially expressed in IDD.

Methods

An lncRNA-mRNA microarray analysis of human nucleus pulposus (NP) was employed. Bioinformatics prediction was also applied to delineate the functional roles of the differentially expressed lncRNAs. Several lncRNAs and mRNAs were chosen for quantitative real-time PCR (qRT-PCR) validation.

Results

Microarray data profiling indicated that 116 lncRNAs (67 up and 49 down) and 260 mRNAs were highly differentially expressed with an absolute fold change greater than ten. Moreover, 1,052 lncRNAs and 1,314 mRNAs were differentially expressed in the same direction in at least four of the five degenerative samples with fold change greater than two. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated a number of pathways, such as extracellular matrix (ECM)-receptor interaction. A coding-noncoding gene co-expression (CNC) network was constructed for the ten most significantly changed lncRNAs. Annotation terms of the coexpressed mRNAs were related to several known degenerative alterations, such as chondrocyte differentiation. Moreover, lncRNAs belonging to a particular subgroup were identified. Functional annotation for the corresponding nearby coding genes showed that these lncRNAs were mainly associated with cell migration and phosphorylation. Interestingly, we found that Fas-associated protein factor-1 (FAF1), which potentiates the Fas-mediated apoptosis and its nearby enhancer-like lncRNA RP11-296A18.3, were highly expressed in the degenerative discs. Subsequent qRT-PCR results confirmed the changes.

Conclusions

This is the first study to demonstrate that aberrantly expressed lncRNAs play a role in the development of IDD. Our study noted that up-regulated RP11-296A18.3 highly likely induced the over-expression of FAF1, which eventually promoted the aberrant apoptosis of disc cells. Such findings further broaden the understanding of the etiology of IDD.
Osteocalcin Protects Against Nonalcoholic Steatohepatitis in a Mouse Model of Metabolic Syndrome
Authors: Gupte Anisha A. , Sabek Omaima M. , Fraga Daniel , Minze Laurie J. , Nishimoto Satoru K. , Liu Joey Z. , Afshar Solmaz , Gaber Lillian , Lyon Christopher J. , Gaber A. Osama , Hsueh Willa A.
Published: October 2014

Nonalcoholic fatty liver disease, particularly its more aggressive form, nonalcoholic steatohepatitis (NASH), is associated with hepatic insulin resistance. Osteocalcin, a protein secreted by osteoblast cells in bone, has recently emerged as an important metabolic regulator with insulin-sensitizing properties. In humans, osteocalcin levels are inversely associated with liver disease. We thus hypothesized that osteocalcin may attenuate NASH and examined the effects of osteocalcin treatment in middle-aged (12-mo-old) male Ldlr−/− mice, which were fed a Western-style high-fat, high-cholesterol diet for 12 weeks to induce metabolic syndrome and NASH. Mice were treated with osteocalcin (4.5 ng/h) or vehicle for the diet duration. Osteocalcin treatment not only protected against Western-style high-fat, high-cholesterol diet-induced insulin resistance but substantially reduced multiple NASH components, including steatosis, ballooning degeneration, and fibrosis, with an overall reduction in nonalcoholic fatty liver disease activity scores. Further, osteocalcin robustly reduced expression of proinflammatory and profibrotic genes (Cd68, Mcp1, Spp1, and Col1a2) in liver and suppressed inflammatory gene expression in white adipose tissue. In conclusion, these results suggest osteocalcin inhibits NASH development by targeting inflammatory and fibrotic processes.
Loss of Tropomodulin4 in the zebrafish mutant träge causes cytoplasmic rod formation and muscle weakness reminiscent of nemaline myopathy
Authors: Berger Joachim , Tarakci Hakan , Berger Silke , Li Mei , Hall Thomas E. , Arner Anders , Currie Peter D.
Published: October 2014

Nemaline myopathy is an inherited muscle disease that is mainly diagnosed by the presence of nemaline rods in muscle biopsies. Of the nine genes associated with the disease, 5 encode for components of striated muscle sarcomeres. In a genetic zebrafish screen the mutant träge (trg) was isolated based on its reduction in muscle birefringence, indicating muscle damage. Myofibres in trg appeared disorganized and showed inhomogeneous cytoplasmic eosin staining alongside malformed nuclei. Linkage analysis of trg combined with sequencing identified a nonsense mutation in tropomodulin4 (tmod4), a regulator of thin filament length and stability. Accordingly, although actin monomers polymerise to form thin filaments in the skeletal muscle of tmod4trg mutants, thin filaments often appeared to be dispersed throughout myofibres. Organised myofibrils with the typical striation rarely assemble, leading to severe muscle weakness, impaired locomotion, and early death. Myofibrils of tmod4trg mutants often featured thin filaments of various lengths, widened Z-disks, undefined H-zones, and electron-dense aggregations of various shapes and sizes. Importantly, Gomori trichrome staining and the lattice pattern of the detected cytoplasmic rods together with the reactivity of rods with phalloidin and an antibody against actinin is reminiscent of nemaline rods found in nemaline myopathy, suggesting that misregulation of thin filament length causes cytoplasmic rod formation in tmod4trg mutants. Although Tropomodulin4 has not been associated with myopathy, the results presented here implicate TMOD4 as a novel candidate for unresolved nemaline myopathies and suggest that the tmod4trg mutant will be a valuable tool to study human muscle disorders.
An integrated transcriptomic and comparative genomic analysis of differential gene expression in Arctic charr (Salvelinus alpinus) following seawater exposure
Authors: Norman Joseph D. , Ferguson Moira M. , Danzmann Roy G.
Published: October 2014

High-throughput RNA sequencing was employed to compare expression profiles in two Arctic charr (Salvelinus alpinus) families post seawater exposure to identify genes and biological processes involved in hypo-osmoregulation and regulation of salinity tolerance. To further understand the genetic architecture of hypo-osmoregulation, the genomic organization of differentially expressed (DE) genes was also analysed. Using a de novo gill transcriptome assembly we found over 2300 contigs to be DE. Major transporters from the seawater mitochondrion-rich cell (MRC) complex were up-regulated in seawater. Expression ratios for 257 differentially expressed contigs were highly correlated between families, suggesting they are strictly regulated. Based on expression profiles and known molecular pathways we inferred that seawater exposure induced changes in methylation states and elevated peroxynitrite formation in gill. We hypothesized that concomitance between DE immune genes and the transition to a hypo-osmoregulatory state could be related to Cl- sequestration by antimicrobial defence mechanisms. Gene Ontology analysis revealed that cell division genes were up-regulated, which could reflect the proliferation of ATP1α1b-type seawater MRCs. Comparative genomics analyses suggest that hypo-osmoregulation is influenced by the relative proximities among a contingent of genes on Arctic charr linkage groups AC-4 and AC-12 that exhibit homologous affinities with a region on stickleback chromosome Ga-I. This supports the hypothesis that relative gene location along a chromosome is a property of the genetic architecture of hypo-osmoregulation. Evidence of non-random structure between hypo-osmoregulation candidate genes was found on AC-1/11 and AC-28, suggesting that interchromosomal rearrangements played a role in the evolution of hypo-osmoregulation in Arctic charr.
Decomposing a Utility Function Based on Discrete Distribution Independence
Authors: He Ying , Dyer James S. , Butler John C.
Published: October 2014

For two-attribute decision-making problems, the multilinear utility model cannot be applied when the risk aversion on one attribute depends on the level of the other attribute. We propose a family of general preference conditions called nth-degree discrete distribution independence that can accommodate a variety of dependence relationships between two attributes. The special case of second-degree discrete distribution independence is equivalent to the utility independence condition. We focus on third-degree discrete distribution independence that leads to a decomposition formula that contains many other preference models as special cases.
Validation of a model-based measurement of the minimum insert thickness of knee prostheses
Authors: van IJsseldijk E. A. , Harman M. K. , Luetzner J. , Valstar E. R. , Stoel B. C. , Nelissen R. G. H. H. , Kaptein B. L.
Published: October 2014

Introduction

Wear of polyethylene inserts plays an important role in failure of total knee replacement and can be monitored in vivo by measuring the minimum joint space width in anteroposterior radiographs. The objective of this retrospective cross-sectional study was to compare the accuracy and precision of a new model-based method with the conventional method by analysing the difference between the minimum joint space width measurements and the actual thickness of retrieved polyethylene tibial inserts.

Method

Before revision, the minimum joint space width values and their locations on the insert were measured in 15 fully weight-bearing radiographs. These measurements were compared with the actual minimum thickness values and locations of the retrieved tibial inserts after revision.

Results

The mean error in the model-based minimum joint space width measurement was significantly smaller than the conventional method for medial condyles (0.50 vs 0.94 mm, p < 0.01) and for lateral condyles (0.06 vs 0.34 mm, p = 0.02). The precision (standard deviation of the error) of the methods was similar (0.84 vs 0.79 mm medially and both 0.46 mm laterally). The distance between the true minimum joint space width locations and the locations from the model-based measurements was less than 10 mm in the medial direction in 12 cases and less in the lateral direction in 13 cases.

Conclusion

The model-based minimum joint space width measurement method is more accurate than the conventional measurement with the same precision. Cite this article: Bone Joint Res 2014;3:289–96
Precision and Reliability of 5 Platelet Function Tests in Healthy Volunteers and Donors on Daily Antiplatelet Agent Therapy
Authors: Karon Brad S , Tolan Nicole V , Koch Christopher D , Wockenfus Amy M , Miller Randall S , Lingineni Ravi K , Pruthi Rajiv K , Chen Dong , Jaffe Allan S
Published: October 2014

BACKGROUND

Anticoagulation protocols used during mechanical circulatory support call for titration of antiplatelet agents. We compared the precision and reliability of 5 platelet function tests in healthy volunteers and donors on daily antiplatelet therapy to distinguish their efficacy for titrating antiplatelet therapy.

METHODS

We assessed arachidonic acid–induced platelet function by light transmission aggregometry (LTA), Multiplate impedance aggregometry, VerifyNow, and platelet mapping by thromboelastography (TEG PM). We assessed ADP-induced platelet function by the same methods and flow cytometry. Forty healthy volunteers and 10–13 volunteers on daily aspirin and/or clopidogrel therapy were evaluated. We compared tests for intraassay precision, interassay precision (samples from 2 separate blood draws), and reliability coefficient.

RESULTS

For arachidonic acid–induced platelet aggregation in healthy volunteers, intra- and interassay CVs were ≤10% for all methods. Intra- and interassay precision among donors on daily aspirin was ≤30% for all methods except LTA (38% interassay CV) and TEG PM (95% intraassay and 104% interassay CV). For ADP-induced platelet function, intra- and interassay precision was ≤10% and ≤30% for all methods. Only Multiplate demonstrated moderate or greater (R > 0.40) reliability coefficients for arachidonic acid–induced platelet function among all subjects. All methods of ADP-induced platelet function, except TEG PM, demonstrated substantial or greater (R > 0.60) reliability among all subjects.

CONCLUSIONS

TEG PM is least suited to monitor effects of antiplatelet agents. Multiplate impedance aggregometry was the only method to demonstrate an acceptable reliability coefficient among healthy volunteers and donors on both aspirin and clopidogrel therapy.