bluuebunny/crossref_metadata_2025 huggingface dataset:
TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients
Authors: Bejar Rafael , Lord Allegra , Stevenson Kristen , Bar-Natan Michal , Pérez-Ladaga Albert , Zaneveld Jacques , Wang Hui , Caughey Bennett , Stojanov Petar , Getz Gad , Garcia-Manero Guillermo , Kantarjian Hagop , Chen Rui , Stone Richard M. , Neuberg Donna , Steensma David P. , Ebert Benjamin L.
Published: September 2014

Key Points

Higher abundance TET2 mutations are associated with increased response to hypomethylating agents, particularly when ASXL1 is not mutated. TP53 and PTPN11 mutations are associated with shorter overall survival after hypomethylating agent treatment, but do not predict response.
Immunohistochemistry as a valuable tool to assess CD30 expression in peripheral T-cell lymphomas: high correlation with mRNA levels
Authors: Bossard Céline , Dobay Maria Pamela , Parrens Marie , Lamant Laurence , Missiaglia Edoardo , Haioun Corinne , Martin Antoine , Fabiani Bettina , Delarue Richard , Tournilhac Olivier , Delorenzi Mauro , Gaulard Philippe , de Leval Laurence
Published: September 2014

Key Points

IHC is a valuable clinical tool for assessing CD30+ PTCL patients who may respond to CD30-targeting treatment. CD30 mRNA and protein expression are highly correlated.
Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers
Authors: Wallin Elizabeth F. , Jolly Elaine C. , Suchánek Ondřej , Bradley J. Andrew , Espéli Marion , Jayne David R. W. , Linterman Michelle A. , Smith Kenneth G. C.
Published: September 2014

Key Points

RTX treatment results in loss of human GC B cells. Human Tfh and Tfr cells do not require GC B cells for their maintenance.
Investigation of extended-gate field-effect transistor pH sensors based on different-temperature-annealed bi-layer MWCNTs-In2O3 films
Authors: Hung Shang-Chao , Cheng Nai-Jen , Yang Cheng-Fu , Lo Yuan-Pin
Published: September 2014

In this paper, indium (In) films were deposited on glass substrates using DC sputtering method. Multiwalled carbon nanotubes (MWCNTs) and dispersant were dissolved in alcohol, and the mixed solution was deposited on the In films using the spray method. The bi-layer MWCNTs-In2O3 films were annealed at different temperatures (from room temperature to 500°C) in O2 atmosphere. The influences of annealing temperature on the characteristics of the bi-layer MWCNTs-In2O3 films were investigated by scanning electron microscopy, X-ray diffraction pattern, Fourier transform infrared (FT-IR) spectroscopy, and Raman spectroscopy. A separative extended-gate field-effect transistor (EGFET) device combined with a bi-layer MWCNTs-In2O3 film was constructed as a pH sensor. The influences of different annealing temperatures on the performances of the EGFET-based pH sensors were investigated. We would show that the pH sensitivity was dependent on the thermal oxygenation temperature of the bi-layer MWCNTs-In2O3 films.
PI3K/Akt regulates survival during differentiation of human macrophages by maintaining NF-κB-dependent expression of antiapoptotic Bcl-xL
Authors: Busca Aurelia , Saxena Mansi , Iqbal Salma , Angel Jonathan , Kumar Ashok
Published: September 2014

Resistance to apoptosis is an important characteristic that human macrophages acquire during differentiation from monocytes. However, the intracellular mechanisms that mediate the development of resistance are not well understood. We have used M-CSF-stimulated primary human monocytes and PMA-treated THP1 cells to study apoptosis resistance during differentiation of human macrophages. Our results indicate that PI3K/Akt distinctively regulates survival of macrophages during and after differentiation. More specifically, a signaling pathway consisting of PI3K/Akt-NF-κB-Bcl-xL regulates cell survival during the differentiation process. PI3K/Akt-mediated activation of NF-κB plays a key role in survival of differentiating macrophages by specifically sustaining antiapoptotic Bcl-xL expression. With the use of pharmacological inhibitors and siRNA for Akt and Bcl-xL, we show that in the absence of Akt-dependent Bcl-xL expression during differentiation, cells undergo caspase-mediated apoptosis. In contrast, in differentiated macrophages, Bcl-xL expression is independent of PI3K/Akt activation. Taken together, these results suggest that survival of macrophages is distinctly regulated during and after differentiation. Our results also suggest new, potential therapeutic targets to modulate differentiation and survival of this cell type.
Prediction of seismic wave dispersion and attenuation from ultrasonic velocity measurements
Authors: Yan Fuyong , Han De-hua , Yao Qiuliang , Zhao Luanxiao
Published: September 2014

Dispersion and attenuation are important attributes of seismic data that can provide important information about reservoir rock lithology, pore fluid type, and pore structure. Based on Cheng’s pore-aspect-ratio spectrum inversion methodology, we related the closure and deformation of soft pores to the measured pressure-dependent porosity data. With this additional constraint, the inverted pore-aspect-ratio spectrum and concentrations are more realistic. The complex pore structure controls two important intrinsic dispersion and attenuation mechanisms: Biot flow and squirt flow. We modified and extended Tang’s unified velocity dispersion and attenuation model and made it applicable to poroelastic media with a complex pore structure under the undrained condition. The inverted pore-aspect-ratio spectra from pressure-dependent ultrasonic velocity measurements were put into the modified Tang’s model to predict velocity dispersion and attenuation in full frequency range at various differential pressure conditions.
Laboratory measurements of seismic attenuation in sandstone: Strain versus fluid saturation effects
Authors: Tisato Nicola , Quintal Beatriz
Published: September 2014

In the past few decades, great attention has been focused on uncovering the physics of seismic wave attenuation in fluid-saturated rocks. However, the relationship among many variables affecting attenuation is still not completely clear. For instance, although the role of strain in enhancing friction dissipation is relatively well known for dry rocks, it remains unclear how and how much it affects attenuation in fluid-saturated rocks. We experimentally measured attenuation in the extensional mode in Berea sandstone at strains between [Formula: see text] and [Formula: see text], and at frequencies in the seismic bandwidth (1–100 Hz). These strains were similar to those typically observed in seismic exploration ([Formula: see text]). We also measured the transient fluid pressure caused when a stepwise stress was applied resulting in such strains. For the studied strain range, our results indicated that: (1) the overall attenuation in dry Berea sandstone increased linearly with strain, (2) the frequency-dependent component of attenuation, which was associated with fluid saturation, was approximately insensitive to strain, and (3) the overall attenuation can be considered as a sum of a frequency-independent and a frequency-dependent components.
Footprint for frequency-domain airborne electromagnetic systems
Authors: Yin Changchun , Huang Xin , Liu Yunhe , Cai Jing
Published: September 2014

An airborne electromagnetic (AEM) survey often covers hundreds of square kilometers. Huge amounts of survey data make 2D/3D data inversion very difficult. However, due to the compact configurations of AEM systems, the sensitive area for each single survey station is much smaller than the whole survey area, which makes it possible to only invert partial survey data. The sensitive area is called the footprint. Based on “moving-footprint” technology, the entire survey can be divided into subareas and the data are first inverted individually and then combined to form the inversions of the entire survey area, so that the cost for forward and inverse modeling can be vastly reduced. Contrary to previous electromagnetic (EM) footprints defined only for an EM transmitter or for a perfectly conductive earth, we defined the frequency-domain AEM footprint by considering a complete AEM transmitter-receiver system over an earth with limited conductivity. We used the tensor Green’s function to calculate the secondary magnetic field from the induced underground current and evaluate the EM footprint as the volume in which the induced current contributes 90% to the total secondary magnetic field at the EM receiver. Numerical experiments for horizontal coplanar and vertical coaxial coil configurations revealed that among all influence factors on the AEM footprint, the flight altitude was dominant, with a high flight altitude corresponding to a large EM footprint, whereas the transmitting frequency and earth resistivity played a secondary role and in a combined way of induction number, with the low frequency or high earth resistivity (small induction number) corresponding to large EM footprints.
Neuroendocrine Prostate Cancer (NEPC) Progressing From Conventional Prostatic Adenocarcinoma: Factors Associated With Time to Development of NEPC and Survival From NEPC Diagnosis—A Systematic Review and Pooled Analysis
Authors: Wang Hai Tao , Yao Yan Hong , Li Bao Guo , Tang Yong , Chang Ji Wu , Zhang Jiao
Published: September 2014

Purpose

An often under-recognized late manifestation of prostate adenocarcinoma (PCa) is the development of treatment-related neuroendocrine prostate cancer (NEPC). The aim of this study is to identify the risk factors related to survival after NEPC diagnosis (NEPCS) and time from initial diagnosis of PCa to development of NEPC (TTNEPC).

Patients and Methods

A literature search on NEPC was performed using databases such as MEDLINE and EMBASE. Studies were eligible if outcomes data (NEPCS and/or TTNEPC) were reported in patients with a prior history of PCa and histopathologically confirmed NEPC. NEPCS and TTNEPC were evaluated using the Cox regression model with the robust sandwich estimates of the covariance matrix.

Results

There were 54 eligible publications, contributing 123 patients. The median TTNEPC was 20 months. In multivariable analyses, the Gleason score was significantly associated with shorter TTNEPC (hazard ratio [HR], 1.66; P = .032). The median NEPCS was 7 months. In multivariable analyses, the number of organs with metastatic disease at NEPC was significantly associated with shorter NEPCS (HR, 3.31; P = .001). Type of treatment after NEPC was significantly associated with longer NEPCS, with HRs of 0.66 (radiotherapy v palliative therapy; P = .034), 0.38 (chemotherapy v palliative therapy; P = .018), and 0.29 (chemoradiotherapy v palliative therapy; P = .012), respectively.

Conclusion

Treatment-related NEPC is an often under-recognized late manifestation of PCa with poor prognosis. Our study found that Gleason score was the only independent factor contributing to TTNEPC. Once NEPC is diagnosed, type of treatment and the number of organs with metastatic disease were the most important factors related to survival.
Single-Nucleotide Polymorphisms Within the Thrombomodulin Gene (THBD) Predict Mortality in Patients With Graft-Versus-Host Disease
Authors: Rachakonda Sivaramakrishna P. , Penack Olaf , Dietrich Sascha , Blau Olga , Blau Igor Wolfgang , Radujkovic Aleksandar , Isermann Berend , Ho Anthony D. , Uharek Lutz , Dreger Peter , Kumar Rajiv , Luft Thomas
Published: September 2014

Purpose

Steroid-refractory graft-versus-host disease (GVHD) is a major and often fatal complication after allogeneic stem-cell transplantation (alloSCT). Although the pathophysiology of steroid refractoriness is not fully understood, evidence is accumulating that endothelial cell stress is involved, and endothelial thrombomodulin (THBD) plays a role in this process. Here we assess whether single-nucleotide polymorphisms (SNPs) within the THBD gene predict outcome after alloSCT.

Patients and Methods

Seven SNPs within the THBD gene were studied (rs1962, rs1042579, rs1042580, rs3176123, rs3176124, rs3176126, and rs3176134) in a training cohort of 306 patients. The relevant genotypes were then validated in an independent cohort (n = 321).

Results

In the training cohort, an increased risk of nonrelapse mortality (NRM) was associated with three of seven SNPs tested: rs1962, rs1042579 (in linkage disequilibrium with rs3176123), and rs1042580. When patients were divided into risk groups (one v no high-risk SNP), a strong correlation with NRM was observed (hazard ratio [HR], 2.31; 95% CI, 1.36 to 3.95; P = .002). More specifically, NRM was predicted by THBD SNPs in patients who later developed GVHD (HR, 3.03; 95% CI, 1.61 to 5.68; P < .001) but not in patients without GVHD. In contrast, THBD SNPs did not predict incidence of acute GVHD. Multivariable analyses adjusting for clinical variables confirmed the independent effect of THBD SNPs on NRM. All findings could be reproduced in the validation cohort.

Conclusion

THBD SNPs predict mortality of manifest GVHD but not the risk of acquiring GVHD, supporting the hypothesis that endothelial vulnerability contributes to GVHD refractoriness.
Cabozantinib in Chemotherapy-Pretreated Metastatic Castration-Resistant Prostate Cancer: Results of a Phase II Nonrandomized Expansion Study
Authors: Smith Matthew R. , Sweeney Christopher J. , Corn Paul G. , Rathkopf Dana E. , Smith David C. , Hussain Maha , George Daniel J. , Higano Celestia S. , Harzstark Andrea L. , Sartor A. Oliver , Vogelzang Nicholas J. , Gordon Michael S. , de Bono Johann S. , Haas Naomi B. , Logothetis Christopher J. , Elfiky Aymen , Scheffold Christian , Laird A. Douglas , Schimmoller Frauke , Basch Ethan M. , Scher Howard I.
Published: September 2014

Purpose

Cabozantinib (XL184), an oral inhibitor of multiple receptor tyrosine kinases such as MET and VEGFR2, was evaluated in a phase II nonrandomized expansion study in castration-resistant prostate cancer (CRPC).

Patients and Methods

Patients received open-label cabozantinib at daily starting doses of 100 mg or 40 mg until disease progression or unacceptable toxicity. The primary end point was bone scan response, defined as ≥ 30% reduction in bone scan lesion area. Other efficacy end points included overall survival, pain, analgesic use, and biomarkers.

Results

One hundred forty-four patients sequentially enrolled in either a 100-mg (n = 93) or 40-mg (n = 51) study cohort. Ninety-one patients (63%) had a bone scan response, often by week 6. Treatment resulted in clinically meaningful pain relief (57% of patients) and reduction or discontinuation of narcotic analgesics (55% of patients), as well as improvements in measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Improvements in each of these outcomes were observed in both cohorts: bone scan response in 73% and 45%, respectively; reductions in measurable soft tissue disease in 80% and 79%, respectively. Median overall survival was 10.8 months for the entire population. Most common grade 3 or 4 adverse events were fatigue (22%) and hypertension (14%). Fewer dose reductions because of toxicity were required in the 40-mg group.

Conclusion

The evidence suggests that cabozantinib has clinically meaningful activity in CRPC. Cabozantinib resulted in improvements in bone scans, pain, analgesic use, measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Taken together, these phase II observations warrant further development of cabozantinib in prostate cancer.
Serum Thyroglobulin (Tg) Monitoring of Patients with Differentiated Thyroid Cancer Using Sensitive (Second-Generation) Immunometric Assays Can Be Disrupted by False-Negative and False-Positive Serum Thyroglobulin Autoantibody Misclassifications
Authors: Spencer Carole , Petrovic Ivana , Fatemi Shireen , LoPresti Jonathan
Published: September 2014

Context:

Reliable thyroglobulin (Tg) autoantibody (TgAb) detection before Tg testing for differentiated thyroid cancer (DTC) is critical when TgAb status (positive/negative) is used to authenticate sensitive second-generation immunometric assay (2GIMA) measurements as free from TgAb interference and when reflexing “TgAb-positive” sera to TgAb-resistant, but less sensitive, Tg methodologies (radioimmunoassay [RIA] or liquid chromatography-tandem mass spectrometry [LC-MS/MS]).

Objective:

The purpose of this study was to assess how different Kronus (K) vs Roche (R) TgAb method cutoffs for “positivity” influence false-negative vs false-positive serum TgAb misclassifications that may reduce the clinical utility of reflex Tg testing.

Methods:

Serum Tg2GIMA, TgRIA, and TgLC-MS/MS measurements for 52 TgAb-positive and 37 TgAb-negative patients with persistent/recurrent DTC were compared. A total of 1426 DTC sera with TgRIA of ≥1.0 μg/L had false-negative and false-positive TgAb frequencies determined using low Tg2GIMA/TgRIA ratios (<75%) to indicate TgAb interference.

Results:

TgAb-negative patients with disease displayed Tg2GIMA, TgRIA, and TgLC-MS/MS serum discordances (% coefficient of variation = 24 ± 20%, range, 0%–100%). Of the TgAb-positive patients with disease, 98% had undetectable/lower Tg2GIMA vs either TgRIA or TgLC-MS/MS (P < .01), whereas 8 of 52 (15%) had undetectable Tg2GIMA + TgLC-MS/MS associated with TgRIA of ≥1.0 μg/L. Receiver operating characteristic curve analysis reported more sensitivity for TgAb method K vs R (81.9% vs 69.1%, P < .001), but receiver operating characteristic curve cutoffs (>0.6 kIU/L [K] vs >40 kIU/L [R]) had unacceptably high false-negative frequencies (22%–32%), whereas false positives approximated 12%. Functional sensitivity cutoffs minimized false negatives (13.5% [K] vs 21.3% [R], P < .01) and severe interferences (Tg2GIMA, <0.10 μg/L) (0.7% [K] vs 2.4% [R], P < .05) but false positives approximated 23%.

Conclusions:

Reliable detection of interfering TgAbs is method and cutoff dependent. No cutoff eliminated both false-negative and false-positive TgAb misclassifications. Functional sensitivity cutoffs were optimal for minimizing false negatives but have inherent imprecision (20% coefficient of variation) that, exacerbated by TgAb biologic variability during DTC monitoring, could cause TgAb status to fluctuate for patients with low TgAb concentrations, prompting unnecessary Tg method changes and disrupting Tg monitoring. Laboratories using reflexing should limit Tg method changes by considering a patient's Tg + TgAb testing history in addition to current TgAb status before Tg method selection.
Use of Aromatase Inhibitors in Large Cell Calcifying Sertoli Cell Tumors: Effects on Gynecomastia, Growth Velocity, and Bone Age
Authors: Crocker Melissa K. , Gourgari Evgenia , Lodish Maya , Stratakis Constantine A.
Published: September 2014

Context:

Large cell calcifying Sertoli cell tumors (LCCSCT) present in isolation or, especially in children, in association with Carney Complex (CNC) or Peutz-Jeghers Syndrome (PJS). These tumors overexpress aromatase (CYP19A1), which leads to increased conversion of delta-4-androstenedione to estrone and testosterone to estradiol. Prepubertal boys may present with growth acceleration, advanced bone age, and gynecomastia.

Objective:

To investigate the outcomes of aromatase inhibitor therapy (AIT) in prepubertal boys with LCCSCTs.

Design:

Case series of a very rare tumor and chart review of cases treated at other institutions.

Setting:

Tertiary care and referral center.

Patients:

Six boys, five with PJS and one with CNC, were referred to the National Institutes of Health for treatment of LCCSCT. All patients had gynecomastia, testicular enlargement, and advanced bone ages, and were being treated by their referring physicians with AIT.

Interventions:

Patients were treated for a total of 6–60 months on AIT.

Main Outcome Measures:

Height, breast tissue mass, and testicular size were all followed; physical examination, scrotal ultrasounds, and bone ages were obtained, and hormonal concentrations and tumor markers were measured.

Results:

Tumor markers were negative. All patients had decreases in breast tissue while on therapy. Height percentiles declined, and predicted adult height moved closer to midparental height as bone age advancement slowed. Testicular enlargement stabilized until entry into central puberty. Only one patient required unilateral orchiectomy.

Conclusions:

Patients with LCCSCT benefit from AIT with reduction and/or elimination of gynecomastia and slowing of linear growth and bone age advancement. Further study of long-term outcomes and safety monitoring are needed but these preliminary data suggest that mammoplasty and/or orchiectomy may be foregone in light of the availability of medical therapy.
The electrostatic profile of consecutive Cβ atoms applied to protein structure quality assessment
Authors: Chakraborty Sandeep , Venkatramani Ravindra , Rao Basuthkar J. , Asgeirsson Bjarni , Dandekar Abhaya M.
Published: September 2014

The structure of a protein provides insight into its physiological interactions with other components of the cellular soup. Methods that predict putative structures from sequences typically yield multiple, closely-ranked possibilities. A critical component in the process is the model quality assessing program (MQAP), which selects the best candidate from this pool of structures. Here, we present a novel MQAP based on the physical properties of sidechain atoms. We propose a method for assessing the quality of protein structures based on the electrostatic potential difference (EPD) of Cβ atoms in consecutive residues. We demonstrate that the EPDs of Cβ atoms on consecutive residues provide unique signatures of the amino acid types. The EPD of Cβ atoms are learnt from a set of 1000 non-homologous protein structures with a resolution cuto of 1.6 Å obtained from the PISCES database. Based on the Boltzmann hypothesis that lower energy conformations are proportionately sampled more, and on Annsen's thermodynamic hypothesis that the native structure of a protein is the minimum free energy state, we hypothesize that the deviation of observed EPD values from the mean values obtained in the learning phase is minimized in the native structure. We achieved an average specificity of 0.91, 0.94 and 0.93 on hg_structal, 4state_reduced and ig_structal decoy sets, respectively, taken from the Decoys `R' Us database. The source code and manual is made available at https://github.com/sanchak/mqap and permanently available on 10.5281/zenodo.7134.
Transitory expression of Dlx5 and Dlx6 in maxillary arch epithelial precursors is essential for upper jaw morphogenesis
Authors: Gitton Yorick , Narboux-Nême Nicolas , Levi Giovanni
Published: September 2014

Asymmetric, articulated jaws are characteristic of most vertebrate species; they derive from the first pharyngeal arch (PA1) which generates both maxillary and mandibular components. PA1 is colonized by cranial neural crest cells (CNCCs) which give rise to most bones and tendons of the jaws. The elements formed by different CNCCs contingents are specified by the combinatorial expression ofDlxgenes.Dlx5andDlx6are predominantly expressed by mandibular CNCCs. Analysis of the phenotype ofDlx5andDlx6double mutant mice has suggested that they are necessary and sufficient to specify mandibular identity. Here, using 3D reconstruction, we show that inactivation ofDlx5andDlx6does not only affect the mandibular arch, but results in the simultaneous transformation of mandibular and maxillary skeletal elements which assume a similar morphology with gain of symmetry. AsDlx5-andDlx6-expressing cells are not found in the maxillary bud, we have examined the lineage ofDlx5-expressing progenitors using anin vivogenetic approach. We find that a contingent of cells deriving from epithelial precursors transiently expressingDlx5participate in the formation of the maxillary arch. These cells are mostly located in the distal part of the maxillary arch and might derive from its lambdoidal junction with the olfactory pit. Our observations provide the first genetic demonstration of the ‘Hinge and Caps’ model[1]. We support the notion that ‘cap’ signals could originate from epithelial derivatives ofDlx5-expressing progenitors which migrate and colonize the maxillary arch epithelium. Our results imply that Dlx5 and Dlx6 control upper and lower jaw morphogenesis through different coordinated mechanisms to generate functional, articulated jaws.
Case Report: Hyponatremia of malignancy – An alternative mechanism? Syndrome of inappropriate atrial natriuretic peptide (SIANP)
Authors: Mansoor Steven Elias , Kagen David I , Kansagara Devan
Published: September 2014

Euvolemic hyponatremia in the setting of lung cancer is most commonly due to the syndrome of inappropriate anti-diuretic hormone secretion (SIADH). However, a subset of patients with small cell carcinoma and hyponatremia also have elevated levels of atrial natriuretic peptide (ANP), which is produced by some small cell tumors. We report the case of a 64-year-old man with a limited-stage small cell carcinoma of the lung undergoing chemoradiation therapy, who was admitted to hospital with a pulmonary embolism. Two months earlier, at the time of diagnosis with lung cancer, he had a hypotonic, euvolemic hyponatremia, presumed to be caused by SIADH. At that time, his serum sodium readily normalized with fluid restriction and ADH-antagonist therapy with demeclocycline. However, during his second admission, the hyponatremia was refractory to treatment: his sodium level slowly declined from 138 mmol/L to a nadir of 118 mmol/L, despite early initiation of fluid restriction and maximal doses of demeclocycline. Laboratory values revealed a low but inappropriately non-zero level of ADH but also an inappropriately low level of aldosterone and an elevated level of ANP, suggesting that SIADH might not be the only contributor to the hyponatremia. While a causal link between ectopic ANP production and hyponatremia has never been established, an inappropriately high level of ANP can directly decrease sodium re-absorption in the proximal convoluted tubule of the kidney and increase glomerular filtration rate (GFR), resulting in greater excretion of sodium and water. In addition, high circulating levels of ANP can inhibit aldosterone secretion, potentially resulting in further sodium wasting. Here, the elevated ANP and inappropriately low aldosterone suggested the possibility that the refractory hyponatremia, although initiated by SIADH, was further worsened by an ANP-mediated natriuresis and suppression of aldosterone response.
Engaging the intermediate tier in ‘A Patient-Led NHS’
Authors: Keep Jane , Sang Bob
Published: September 2014

This article reflects on recent work of the Engaging Communities Learning Network, that shed important light on the present organisational development challenges for the NHS.

Are organisations fully engaging in ‘A patient-led NHS’?
Supporting students with additional needs in Scotland
Authors: Friswell Jane
Published: September 2014

The Advisory Group for Additional Support for Learning advises ministers on the implementation of legislation and policy. Nasen's Jane Friswell updates us on its work and outlines some key priorities for the year ahead.
Getting it right the first time: how to select stoma accessories
Authors: Hayles Kevin
Published: September 2014

Ensuring a high quality of life for all patients who have undergone stoma surgery (ostomists) is fundamental to stoma care nurses. This includes making sure that any problems encountered by ostomists are dealt with appropriately, using expert knowledge at all times. With this in mind, it is important for stoma care nurses to be updated on the various types of stoma accessories available. The author will detail some of the more common accessories available and their use in maintaining a patient's skin integrity and improving pouch adhesion and pouch security, thus helping to improve the patient's quality of life.
Quantification of HDL Particle Concentration by Calibrated Ion Mobility Analysis
Authors: Hutchins Patrick M , Ronsein Graziella E , Monette Jeffrey S , Pamir Nathalie , Wimberger Jake , He Yi , Anantharamaiah G M , Kim Daniel Seung , Ranchalis Jane E , Jarvik Gail P , Vaisar Tomas , Heinecke Jay W
Published: September 2014

BACKGROUND

It is critical to develop new metrics to determine whether HDL is cardioprotective in humans. One promising approach is HDL particle concentration (HDL-P), the size and concentration of HDL in plasma. However, the 2 methods currently used to determine HDL-P yield concentrations that differ >5-fold. We therefore developed and validated an improved approach to quantify HDL-P, termed calibrated ion mobility analysis (calibrated IMA).

METHODS

HDL was isolated from plasma by ultracentrifugation, introduced into the gas phase with electrospray ionization, separated by size, and quantified by particle counting. We used a calibration curve constructed with purified proteins to correct for the ionization efficiency of HDL particles.

RESULTS

The concentrations of gold nanoparticles and reconstituted HDLs measured by calibrated IMA were indistinguishable from concentrations determined by orthogonal methods. In plasma of control (n = 40) and cerebrovascular disease (n = 40) participants, 3 subspecies of HDL were reproducibility measured, with an estimated total HDL-P of 13.4 (2.4) μmol/L. HDL-C accounted for 48% of the variance in HDL-P. HDL-P was significantly lower in participants with cerebrovascular disease (P = 0.002), and this difference remained significant after adjustment for HDL cholesterol concentrations (P = 0.02).

CONCLUSIONS

Calibrated IMA accurately determined the concentration of gold nanoparticles and synthetic HDL, strongly suggesting that the method could accurately quantify HDL particle concentration. The estimated stoichiometry of apolipoprotein A-I determined by calibrated IMA was 3–4 per HDL particle, in agreement with current structural models. Furthermore, HDL-P was associated with cardiovascular disease status in a clinical population independently of HDL cholesterol.
YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population: Cohort and Mendelian Randomization Studies
Authors: Kjaergaard Alisa D , Bojesen Stig E , Nordestgaard Børge G , Johansen Julia S
Published: September 2014

BACKGROUND

We tested the hypothesis that observationally and genetically increased YKL-40 concentrations are associated with alcoholic liver and pancreas damage and disease.

METHODS

We performed cohort and mendelian randomization in 86 258 individuals from the Danish general population, with measured concentrations of plasma YKL-40 (n = 21 646) and CHI3L1 rs4950928 genotype (n = 84 738).

RESULTS

Increased YKL-40 was associated with increased alanine aminotransferase, bilirubin, alkaline phosphatase, γ-glutamyl transferase, erythrocyte mean corpuscular volume, C-reactive protein, and fibrinogen and with decreased albumin; coagulation factors II, VII, and X; and pancreatic amylase. The multifactorially adjusted hazard ratio for alcoholic liver cirrhosis comparing the 96%–100% vs 0%–33% YKL-40 percentile categories was 41 (95% CI 14–118). Corresponding ratios were 7.9 (5.1–12) for any alcoholic liver disease, 4.1 (1.7–10) for alcoholic pancreatitis, and 3.4 (1.9–6.1) for any pancreatitis. CHI3L1 rs4950928 genotype explained 14% of the variation in plasma YKL-40 concentrations but was not associated with alcoholic liver and pancreas damage or disease. A doubling in YKL-40 concentrations was associated with a multifactorially adjusted observational hazard ratio of 2.8 (2.4–3.3) for alcoholic liver cirrhosis and a corresponding genetic odds ratio of 1.1 (0.7–1.5). Corresponding risk estimates were 2.0 (1.8–2.2) observationally and 1.0 (0.8–1.1) genetically for any alcoholic liver disease, 1.4 (1.1–1.9) observationally and 1.1 (0.8–1.5) genetically for alcoholic pancreatitis, and 1.3 (1.1–1.6) observationally and 1.0 (0.8–1.3) genetically for any pancreatitis. Excessive alcohol consumption combined with YKL-40 concentrations in the top 5% was associated with 10-year risk of alcoholic liver cirrhosis of up to 7% in ever-smokers and 2% in never-smokers.

CONCLUSIONS

YKL-40 concentration within the top 5% was a marker for alcoholic liver cirrhosis, with no evidence to support a causal relationship.
DNA-bound metal ions: recent developments
Authors: Morris Daniel L.
Published: September 2014

The affinity of metal ions for DNA is logical considering that the structure of DNA includes a phosphate backbone with a net-negative charge, a deoxyribose sugar with O atoms, and purine and pyrimidine bases that contain O and N atoms. DNA-metal ion interactions encompass a large area of research that ranges from the most fundamental characterization of DNA-metal ion binding to the role of DNA-bound metal ions in disease and human health. Alternative DNA base pairing mediated by metal binding is also being investigated and manipulated for applications in logic gates, molecular machines, and nanotechnology. This review highlights recent work aimed at understanding interactions of redox-active metal ions with DNA that provides a better understanding of the mechanisms by which various types of oxidative DNA damage (strand breakage and base modifications) occur. Antioxidants that mitigate oxidative DNA damage by coordinating metal ions that produce reactive oxygen species are addressed, as well as recent work on the effect of DNA-metal ion interactions and the efficacy of quinolone-based antibacterial drugs. Recent advances in metal-mediated base pairing that triggers conformational changes in DNA structure for use as selective metal ion sensors and novel nanotechnology applications are also included.
Recent trends in synthesis of five- and six-membered heterocycles using dimethyl N-cyanodithioiminocarbonate
Authors: Elgemeie Galal H. , Mohamed Reham A.
Published: September 2014

New approaches to synthesis of five- and six-membered heterocyclic compounds utilizing dimethyl N-cyanodithioiminocarbonate are surveyed. The scope and limitation of the most important approaches are discussed.
A Load Frequency Control in an Off-Grid Sustainable Power System Based on a Parameter Adaptive PID-Type Fuzzy Controller
Authors: Ronilaya Ferdian , Miyauchi Hajime
Published: September 2014

This paper presents a new implementation of a parameter adaptive PID-type fuzzy controller (PAPIDfc) for a grid-supporting inverter of battery to alleviate frequency fluctuations in a wind-diesel power system. A variable speed wind turbine that drives a permanent magnet synchronous generator is assumed for demonstrations. The PAPIDfc controller is built from a set of control rules that adopts the droop method and uses only locally measurable frequency signal. The output control signal is determined from the knowledge base and the fuzzy inference. The input-derivative gain and the output-integral gain of the PAPIDfc are tuned online. To ensure safe battery operating limits, we also propose a protection scheme called intelligent battery protection (IBP). Several simulation experiments are performed by using MATLAB®/SimPowersystems™. Next, to verify the scheme’s effectiveness, the simulation results are compared with the results of conventional controllers. The results demonstrate the effectiveness of the PAPIDfc scheme to control a grid-supporting inverter of the battery in the reduction of frequency fluctuations.
Sleep-related behaviors in Alzheimer’s disease and dementia with Lewy bodies
Authors: Raggi Alberto , Neri Walter , Ferri Raffaele
Published: September 2014

Prevalence studies suggest that Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the most common dementing illnesses in the elderly. The aim of this narrative review was to provide data on sleep-related behaviors in AD and DLB. This paper contains arguments, with a clinical approach, on both circadian rhythm changes and dissociated states of wakefulness and sleep in these two conditions.
Ack kinase regulates CTP synthase filaments during Drosophila oogenesis
Authors: Strochlic Todd I , Stavrides Kevin P , Thomas Sam V , Nicolas Emmanuelle , O'Reilly Alana M , Peterson Jeffrey R
Published: September 2014

The enzyme CTP synthase (CTPS) dynamically assembles into macromolecular filaments in bacteria, yeast, Drosophila, and mammalian cells, but the role of this morphological reorganization in regulating CTPS activity is controversial. During Drosophila oogenesis, CTPS filaments are transiently apparent in ovarian germline cells during a period of intense genomic endoreplication and stockpiling of ribosomal RNA. Here, we demonstrate that CTPS filaments are catalytically active and that their assembly is regulated by the non‐receptor tyrosine kinase DAck, the Drosophila homologue of mammalian Ack1 (activated cdc42‐associated kinase 1), which we find also localizes to CTPS filaments. Egg chambers from flies deficient in DAck or lacking DAck catalytic activity exhibit disrupted CTPS filament architecture and morphological defects that correlate with reduced fertility. Furthermore, ovaries from these flies exhibit reduced levels of total RNA, suggesting that DAck may regulate CTP synthase activity. These findings highlight an unexpected function for DAck and provide insight into a novel pathway for the developmental control of an essential metabolic pathway governing nucleotide biosynthesis.
Cholesterol in brain disease: sometimes determinant and frequently implicated
Authors: Martín Mauricio G , Pfrieger Frank , Dotti Carlos G
Published: September 2014

Cholesterol is essential for neuronal physiology, both during development and in the adult life: as a major component of cell membranes and precursor of steroid hormones, it contributes to the regulation of ion permeability, cell shape, cell–cell interaction, and transmembrane signaling. Consistently, hereditary diseases with mutations in cholesterol‐related genes result in impaired brain function during early life. In addition, defects in brain cholesterol metabolism may contribute to neurological syndromes, such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD), and even to the cognitive deficits typical of the old age. In these cases, brain cholesterol defects may be secondary to disease‐causing elements and contribute to the functional deficits by altering synaptic functions. In the first part of this review, we will describe hereditary and non‐hereditary causes of cholesterol dyshomeostasis and the relationship to brain diseases. In the second part, we will focus on the mechanisms by which perturbation of cholesterol metabolism can affect synaptic function.
Etiologies for Seizures Around the Time of Vaccination
Authors: Verbeek Nienke E. , Jansen Floor E. , Vermeer-de Bondt Patricia E. , de Kovel Carolien G. , van Kempen Marjan J.A. , Lindhout Dick , Knoers Nine V.A.M. , van der Maas Nicoline A.T. , Brilstra Eva H.
Published: September 2014

OBJECTIVES:

This study was an assessment of the incidence, course, and etiology of epilepsy with vaccination-related seizure onset in a population-based cohort of children.

METHODS:

The medical data of 990 children with seizures after vaccination in the first 2 years of life, reported to the National Institute for Public Health and Environment in the Netherlands in 1997 through 2006, were reviewed. Follow-up data were obtained of children who were subsequently diagnosed with epilepsy and had had seizure onset within 24 hours after administration of an inactivated vaccine or 5 to 12 days after a live attenuated vaccine.

RESULTS:

Follow-up was available for 23 of 26 children (median age: 10.6 years) with epilepsy onset after vaccination. Twelve children developed epileptic encephalopathy, 8 had benign epilepsy, and 3 had encephalopathy before seizure onset. Underlying causes were identified in 15 children (65%) and included SCN1A–related Dravet syndrome (formerly severe myoclonic epilepsy of infancy) or genetic epilepsy with febrile seizures plus syndrome (n = 8 and n = 1, respectively), a protocadherin 19 mutation, a 1qter microdeletion, neuronal migration disorders (n = 2), and other monogenic familial epilepsy (n = 2).

CONCLUSIONS:

Our results suggest that in most cases, genetic or structural defects are the underlying cause of epilepsy with onset after vaccination, including both cases with preexistent encephalopathy or benign epilepsy with good outcome. These results have significant added value in counseling of parents of children with vaccination-related first seizures, and they might help to support public faith in vaccination programs.
Safety of Live-Attenuated Influenza Vaccination in Cystic Fibrosis
Authors: Boikos Constantina , De Serres Gaston , Lands Larry C. , Boucher François D. , Tapiéro Bruce , Daigneault Patrick , Quach Caroline
Published: September 2014

OBJECTIVES:

Given the improved efficacy of the nasal live-attenuated influenza virus vaccine (LAIV) compared with the injectable vaccine in children, we aimed to determine its safety in individuals with cystic fibrosis (CF).

METHODS:

A cohort of 168 study participants, aged 2 to 18 years with CF, vaccinated with LAIV between October 1, 2012, and January 30, 2013, was followed prospectively for 56 days after initial vaccination in 3 pediatric CF clinics across the province of Quebec. Days 0 to 28 post-LAIV were considered the at-risk period for all outcomes of interest, and days 29 to 56 post-LAIV were considered the non–at-risk period. Incident respiratory deteriorations were defined as an unscheduled medical visit, hospitalization, or a new course of oral antibiotics for respiratory complaints. Using a self-controlled design, incidence rate ratios (IRR) were used to compare at-risk and non–at-risk periods.

RESULTS:

Comparing at-risk to non–at-risk periods, there was no significant increase in the rate of incident respiratory deteriorations (IRR, 0.72; 95% confidence interval, 0.11–4.27) or all-cause hospitalizations (IRR, 1.16; 95% confidence interval, 0.30–4.81). A greater proportion of participants reported experiencing at least 1 minor respiratory and/or systemic adverse event after immunization during the at-risk period compared with the non–at-risk period (77% vs 54%, respectively). During the first week after LAIV, 13 of 168 (8%) children reported some wheezing, with the vast majority, 9 of 13 (69%), on the day of vaccination.

CONCLUSIONS:

There was no increased risk of respiratory deterioration or all-cause hospitalization associated with LAIV in our study population. LAIV seems well tolerated in children and adolescents with CF.
DIAGNOSTICO SOCIOECONOMICO Y DE SALUD DE CUATRO COMUNIDADES INDIGENAS DEL MUNICIPIO HUAUTLA: UN SUSTENTO PARA LA VINCULACION DE LA CARRERA DE ENFERMERIA DEL CECYTEH
Authors: Bravo Vargas Diana , Nochebuena Nochebuena Guillermo
Published: September 2014

Esteartículopresentalosresultadosdeunestudiosocioeconómicoydesalud conelobjetivodecontarconuna base de datos de cuatro comunidades cercanas al Colegio de Estudios Científicos y Tecnológicos del Estado de Hidalgo (CECyTEH). La propuesta fue pensada desde la perspectiva de la Enfermería Social, la Teoría del Autocuidado y la Vinculación Educativa. Metodología: El estudio es de tipo exploratorio y descriptivo. Se aplicó el método teórico de análisis-síntesis. Se utilizó una encuesta que exploró dos dimensiones: socioeconómica y de salud. Además, se empleó el muestreo aleatorio estratificado con un nivel de confiabilidad de 95% y 3% de margen de error y con base en el número de hogares por comunidad reportados por el INEGI, 2000. La muestra es de 79 hogares seleccionados. Se realizó una valoración cuantitativa y cualitativa. Resultado: de la encuesta hecha a las comunidades, se comprobó que hay una población indígena con un alto grado de vulnerabilidad y rezago social. Los padecimientos más frecuentes son la Diabetes mellitus, Hipertensión y problemas del miocardio, artritis, reumatismo y problemas renales. Conclusión: un programa de vinculación educativa, operado desde la perspectiva de la enfermería comunitaria es urgente y factible de realizar. Es necesario que se efectúe una propuesta económica de vinculación en la que las funciones del colegio tienen que ser aprovechadas por la comunidad.
EL APRENDIZAJE BASADO EN PROBLEMAS PARA LA INTERVENCION DE LA ENFERMERIA CON LA PERSONA ADULTA MAYOR
Authors: Mora Escalante Elena
Published: September 2014

El aprendizaje basado en problemas se origina en universidades como Case Western Reserve, en los Estados Unidos, la Universidad de McMaster, en Canadá, de modo que otros centros universitarios en el mundo lo han integrado como metodología de enseñanza y aprendizaje en diversas áreas del conocimiento y en distintas carreras. Por lo anterior, la Universidad de Costa Rica, a través del Departamento de Docencia Universitaria, elaboró el curso “Aprendizaje Basado en Problemas” dirigido a las y los profesores con el fin de desarrollar competencias docentes para su utilización. Luego de haber participado en dicho curso, nace la inquietud de realizar el presente ensayo para reflexionar sobre el ABP y su aplicación como técnica didáctica en el Módulo Intervención de Enfermería con la Adultez Mayor, la cual pertenece a la carrera de Enfermería de la Universidad de Costa Rica. El ABP es una estrategia de enseñanza – aprendizaje en la que la adquisición del conocimiento y el desarrollo de habilidades y actitudes tienen la misma importancia debido que buscan facilitar la formación del estudiante y desarrollar un razonamiento y el juicio crítico que le permitan enfrentarse a los desafíos de la vida profesional, todos aspectos relevantes que se contemplan en el módulo.
CREACIÓN DE LA CONSULTA DE ENFERMERIA PEDIÁTRICA EN LOS CENTROS INFANTILES DE LA ASOCIACION DE ROBLEALTO
Authors: Leiva Díaz Viriam , González Quirós Mónica
Published: September 2014

Esta investigación tuvo como objetivo analizar el aporte obtenido al crear la consulta de Enfermería Pediátrica que se ofrece a los niños, niñas y preadolescentes de alto riesgo de los centros infantiles de la Asociación Roblealto. Inicialmente, se diagnosticaron las necesidades de la población en estudios para, luego, poder implementar la consulta de Enfermería Pediátrica en tres centros infantiles con el fin de evaluar su respectivo funcionamiento. Este trabajo fue una investigación aplicada, con un enfoque mixto. Entre los principales hallazgos se mencionan las necesidades educativas que tienen las madres que reciben el servicio en los centros infantiles en relación con el cuidado de sus hijos e hijas, razón por la cual requerían de un profesional en el área de Enfermería Pediátrica para identificar e intervenir en las dificultades que puedan limitar el adecuado crecimiento y desarrollo de los infantes y preadolescentes. Al finalizar la consulta de Enfermería Pediátrica en los centros infantiles se evidencia la viabilidad de la intervención, ya que se observaron resultados positivos en los niños, niñas, preadolescentes y sus familias, por otra parte, la propuesta responde favorablemente a las políticas de salud en la atención del menor de edad en riesgo social. Conclusión: tras la consulta, se obtuvieron resultados positivos en los niños, niñas, preadolescentes y sus familias, ya que el recurso especializado representa un excelente medio para asesorar en cuanto a la educación en salud.