bluuebunny/crossref_metadata_2025 huggingface dataset:
Extended theory for orbital drilling (helical drill‐milling)
Authors: Fangmann S. , Meyer I. , Brinksmeier E.
Published: June 2011

Beim Orbitalbohren bewegt sich das Werkzeug (spezieller Schaftfräser) relativ zum Werkstück auf einer Helixbahn. Durch die dreidimensionale Werkzeugbahn und die überlagerte rotierende Schnittbewegung des Werkzeugs entsteht am Werkstück eine komplexe Bearbeitungstopographie, die die zerspantechnische Eingriffsbedingung des Werkzeugs vorgibt. Die daraus resultierenden Eingriffsbedingungen wurden in der Arbeit “Orbital Drilling Kinematics [1]” hergeleitet. In diesem Artikel werden zwei neue Themenschwerpunkte, die sich aus den Ergebnissen vorangegangener Veröffentlichungen ergeben haben, behandelt. Im ersten Teil werden die bisherigen theoretischen Erkenntnisse mit dem Inhalt einer nahezu parallel entstandenen Veröffentlichung verglichen und diskutiert. Im zweiten Teil wird das bisherige theoretische Modell, welches sich zur Berechnung der Spanungsquerschnitte von Mantel‐ und Stirnschnitt auf den Bohrungsmittelpunkt bezieht, weiterentwickelt. Die Erweiterung des bisherigen Modells erfolgt mit der Zielsetzung eine mathematische Beschreibung der Schnittzonen in Abhängigkeit zum Werkzeugmittelpunkt herzuleiten. Mit dieser Beschreibung wird es möglich, einen mathematischen Bezug von aktuellem Eingriffswinkel und zugehörigem Spanungsquerschnitt des Werkzeugs zu formulieren. Abschließend werden Ansätze für die Entwicklung eines Zerspankraftmodells für das Orbitalbohren aufgezeigt.
Experimental investigation of microsegregation in low frequency electromagnetic casting 7075 aluminum alloy
Authors: Chen D. , Zhang H. , Jiang H. , Cui J.
Published: June 2011

7075 aluminum alloy ingots were prepared by the process of low frequency electromagnetic casting (low frequency electromagnetic casting = LFEC) and conventional direct chill (direct chill = DC) casting, respectively. The effects of low frequency electromagnetic field on microsegregation were investigated from eutectic analysis and electro probe microanalysis (EPMA). It was found that the amount of the eutectic, which was composed of α‐Al (aluminum phase), T phase and MgZn2 was decreased markedly. In contrast, the solute concentration profiles which depend on solid fraction were increased to a certain extent with the presence of low frequency electromagnetic field. The effective distribution coefficient ke was calculated, and the values of ke for solutes in the LFEC sample were bigger than those in the DC sample. The LFEC process alleviated the microsegregation in 7075 aluminum alloy.
Are the yips a task‐specific dystonia or “golfer's cramp”?
Authors: Adler Charles H. , Crews Debra , Kahol Kanav , Santello Marco , Noble Brie , Hentz Joseph G. , Caviness John N.
Published: June 2011

This study compared golfers with and without the yips using joint movement and surface electromyographic detectors. Fifty golfers (25 with and 25 without complaints of the yips) were studied while putting. All putts were videotaped. Surface electromyography assessed arm cocontraction. A CyberGlove II (Immersion Technologies, Palo Alto, CA) assessed right‐arm angular movements. Primary analysis was done by subjective complaint of the yips, whereas secondary analysis was done by video evidence of an involuntary movement. When grouped by subjective complaints, there were no differences in any movement parameter. When grouped by video evidence of an involuntary movement, yips cases had more (P < 0.001) angular movement in wrist pronation/supination and a trend (P = 0.08) for wrist flexor/extensor cocontraction (yips: 7 of 17, 41.2%; no yips: 6 of 33, 18.2%). Golfers with video evidence of an involuntary movement while putting have excessive rotation of the right wrist in a pronation/supination motion and, as previously reported, a trend for wrist flexor/extensor cocontraction. © 2011 Movement Disorder Society
Signaling pathways in ascidian oocyte maturation: The roles of cAMP/Epac, intracellular calcium levels, and calmodulin kinase in regulating GVBD
Authors: Lambert Charles C.
Published: June 2011

Most mature ascidian oocytes undergo germinal vesicle breakdown (GVBD) when released by the ovary into sea water (SW). Acidic SW blocks this but they can be stimulated by raising the pH, increasing intracellular cAMP levels by cell permeant forms, inhibiting its breakdown or causing synthesis. Boltenia villosa oocytes undergo GVBD in response to these drugs. However, the cAMP receptor protein kinase A (PKA) does not appear to be involved, as oocytes are not affected by the kinase inhibitor H‐89. Also, the PKA independent Epac agonist 8CPT‐2Me‐cAMP stimulates GVBD in acidic SW. GVBD is inhibited in calcium free sea water (CaFSW). The intracellular calcium chelator BAPTA‐AM blocks GVBD at 10 µM. GVBD is also inhibited when the ryanodine receptors (RYR) are blocked by tetracaine or ruthenium red but not by the IP3 inhibitor D‐609. However, dimethylbenzanthracene (DMBA), a protein kinase activator, stimulates GVBD in BAPTA, tetracaine or ruthenium red blocked oocytes. The calmodulin kinase inhibitor KN‐93 blocks GVBD at 10 µM. This and preceding papers support the hypothesis that the maturation inducing substance (MIS) produced by the follicle cells in response to increased pH causes activation of a G protein which triggers cAMP synthesis. The cAMP then activates an Epac molecule, which causes an increase in intracellular calcium from the endoplasmic reticulum ryanodine receptor. The increased intracellular calcium subsequently activates calmodulin kinase, which causes an increase in cdc25 phosphatase activity, activating MPF and the progression of the oocyte into meiosis. Mol. Reprod. Dev. 78:726–733, 2011. © 2011 Wiley Periodicals, Inc.
Identification of developmental competence‐related genes in mature porcine oocytes
Authors: Yuan Ye , Ida Jennifer M. , Paczkowski Melissa , Krisher Rebecca L.
Published: June 2011

Oocyte competence is a key factor limiting female fertility, yet the underlying molecular mechanisms that contribute to oocyte competence remain unclear. The objective of this study was to elucidate specific genes whose function contributes to oocyte competence. We observed that 6 of 20 target genes examined were differentially expressed between adult (more competent) and prepubertal (less competent) porcine in vitro matured (IVM) oocytes. These genes were the cholesterol synthesis‐related gene HMG‐CoA reductase (HMGCR), fatty acid oxidation genes acyl‐CoA synthetase long‐chain family member 3 (ACSL3) and long‐chain acyl‐CoA dehydrogenase (ACADL), glycolytic genes fructose 1,6 bisphosphate aldolase (ALDOA) and lactate dehydrogenase C (LDHC), and tumor necrosis factor‐α (TNF). These 6 genes, as well as 3 other genes [porcine endogenous retrovirus (PERV), transcribed loci 10 (TL10), serine/arginine‐rich splicing factor 1 (SRSF1)], were further analyzed by comparing transcript abundance in IVM and in vivo matured (VVM) prepubertal and adult porcine oocytes. Among these 9 target genes, 5 were differentially expressed between IVM and VVM prepubertal oocytes, while 8 genes were differentially expressed between IVM and VVM adult oocytes. No genes were differentially expressed between VVM prepubertal and adult oocytes. A functional study of TNF demonstrated that depletion of endogenous TNF decreased oocyte competence and TNFAIP6 expression in cumulus cells, while TNF in IVM medium regulated TNFAIP6 expression in cumulus cells. Differential expression of the genes identified in this study suggests that these genes may be functionally relevant to oocyte competence. Mol. Reprod. Dev. 78:565–575, 2011. © 2011 Wiley‐Liss, Inc.
Sonographic features in hereditary neuropathy with liability to pressure palsies
Authors: Hooper Davyd R. , Lawson Wendy , Smith Lisa , Baker Steven K.
Published: June 2011

Introduction: Diagnostic nerve ultrasound is becoming more commonly used by both radiologists and clinicians. The features of different neuromuscular conditions must be described to broaden our understanding and ability to interpret findings. Methods: Our study examines the sonographic features of 7 subjects with hereditary neuropathy with liability to pressure palsies (HNPP) in comparison to 32 controls by measuring the nerve cross‐sectional area (CSA) of the median, ulnar and tibial nerves. Results: Significant differences (P < 0.05) in nerve size were found. The HNPP group had a larger CSA for the median nerve at the wrist and ulnar nerve at the elbow (entrapment sites), but not the forearms. The tibial nerve at the ankle was also larger in the HNPP group, suggesting possible concomitant tibial neuropathy at the ankle. Conclusion: These results will help shape imaging protocols to better detect conditions with non‐uniform nerve enlargements. Muscle Nerve 2011
Expanding the phenotype of late‐onset pompe disease: Tongue weakness: A new clinical observation
Authors: Dubrovsky Alberto , Corderi Jose , Lin Min , Kishnani Priya S. , Jones Harrison N.
Published: June 2011

Introduction: Following the clinical observation of lingual weakness in 2 patients with late‐onset Pompe disease (LOPD), tongue strength was assessed in 19 consecutive patients to determine the frequency and severity of this neurological sign. Methods: Lingual strength was assessed using manual muscle testing; if weakness was present, severity was established as mild, moderate, or severe. Results: All the patients exhibited lingual weakness, even 2 asymptomatic patients with a positive family history. Weakness was mild in 12 (63%), moderate in 6 (32%), and severe in 1 (5%). Dysarthria and/or dysphagia were observed or reported in 7 of 19 (37%) patients. Conclusions: Lingual weakness may be present as an axial sign of LOPD, even relatively early in the disease course, and may contribute to the differential diagnosis of this now treatable condition. Dysphagia and/or dysarthria may also occur. This finding further expands the phenotype of LOPD. Muscle Nerve, 2011
Concentric needle jitter on stimulated frontalis and extensor digitorum in 20 myasthenia gravis patients
Authors: Aris Kouyoumdjian João , Fanani Adriana Cristina da Silva , Stålberg Erik V.
Published: June 2011

Introduction: Our objective was to study jitter parameters using a concentric needle electrode (CNE) in the extensor digitorum (ED) and frontalis (FR) muscles. Methods: Twenty myasthenia gravis (MG) patients, mean age 44.5 years, were studied. Percutaneous (FR) and intramuscular needle (ED) stimulation approaches were used. Jitter was expressed as the mean consecutive difference (MCD). The filter settings were from 1000 HZ to 10 kHZ. Results: Abnormal MCD was found in 85% for both ED and FR and in 90% when combining the two muscles. An abnormal percentage of outliers was found in 90% for ED and 85% for FR. The mean MCD did not show a difference for ED and FR, but the percentage of outliers and blocking were higher in FR. Abnormality was found in 93.7% (generalized) and in 75% (ocular) of MG cases. For ED outliers abnormality was greater than the MCD. Conclusion: CNE jitter is reliable for investigation of MG, although borderline findings should be judged with caution. Muscle Nerve 2011
Researching bladder afferents—determining the effects of β3‐adrenergic receptor agonists and botulinum toxin type‐A
Authors: Kanai Anthony , Wyndaele Jean‐Jacques , Andersson Karl‐Erik , Fry Christopher , Ikeda Youko , Zabbarova Irina , De Wachter Stefan
Published: June 2011

A substantial portion of the current research on lower urinary tract dysfunction is focused on afferent mechanisms. The main goals are to define and modulate the signaling pathways by which afferent information is generated, enhanced and conveyed to the central nervous system. Alterations in bladder afferent mechanisms are a potential source of voiding dysfunction and an emerging source for drug targets. Established drug therapies such as muscarinic receptor antagonists, and two emerging therapies, β3‐adrenergic receptor agonists and botulinum toxin type‐A, may act partly through afferent mechanisms. This review focuses on these two new principles and new and established methods for determining their sites of action. It also provides brief information on the innervation of the bladder, afferent receptors and transmitters and how these may communicate with the urothelium, interstitial cells and detrusor smooth muscle to regulate micturition. Peripheral and central mechanisms of afferent sensitization and myogenic mechanisms that lead to detrusor overactivity, overactive bladder symptoms and urgency sensations are also covered. This work is the result from ‘Think Tank’ presentations, and the lengthy discussions that followed, at the 2010 International Consultation on Incontinence Research Society meeting in Bristol, UK. Neurourol. Urodynam. Neurourol. Urodynam. 30:684–691, 2011. © 2011 Wiley‐Liss, Inc.
SUI surgery at the time of vaginal POP repair: Is a surgical algorithm possible or desirable?
Authors: Goldman Howard B.
Published: June 2011

Aims

To review the question of whether SUI Surgery should be performed at the time of vaginal POP repair and whether a surgical algorithm is possible and report discussion on this topic from the ICI‐RS meeting in 2010.

Methods

The literature on this topic was surveyed and discussion from ICI‐RS is reported.

Results

There are multiple approaches to this question with literature supporting each of these approaches. Some perform an anti‐incontinence procedure in all patients undergoing vaginal surgery, many are selective and only perform it in patients with symptoms or signs (including occult) of SUI and some perform it in no patients preferring to wait and see if they have symptoms of SUI post‐operatively. There are a number of algorithms in use reflecting these practices but none agreed on by all. Ongoing trials may provide more information that allows the construction of better algorithms. All agreed that preoperative counseling was critical.

Conclusion

Surgical practice regarding SUI surgery at the time of vaginal POP repair varies widely and there is conflicting literature that supports different approaches and algorithms. Ongoing trials should provide more information to help construct better algorithms. Other approaches for designing prediction models for this problem may be useful.

Neurourol. Urodynam. 30:758–761, 2011. © 2011 Wiley‐Liss, Inc.
Expression of apoptotic factors in vaginal tissues from women with urogenital prolapse
Authors: Wen Yan , Ho Jason Yen‐Ping , Polan Mary Lake , Chen Bertha
Published: June 2011

Aims

Increased apoptotic activity in pelvic tissues may contribute to development of pelvic floor disorders. We evaluated expression of apoptotic factors (Bcl‐2 family) in vaginal tissues from women with pelvic organ prolapse (POP) and how these factors correlate with severity of prolapse.

Methods

mRNA and protein expression of anti‐apoptotic and pro‐apoptotic factors in vaginal tissues from subjects and controls were determined by real‐time PCR and Western blot. Severity of prolapse was staged using POP‐Q criteria.

Results

Differential expression of Bcl‐2 family factors was observed in protein rather than in gene expression. During the secretory phase, the anti‐apoptotic (Bcl‐2, Bcl‐xl) and pro‐apoptotic protein (Bax) were upregulated in controls compared to cases (P < 0.05). The ratios of Bcl‐2/Bax and Bcl‐2/Bad, which determine cellular sensitivity to induction of apoptosis, were higher in controls versus cases. Higher ratios indicate reduced cellular sensitivity to apoptosis. Protein expression of Bax and Bad was higher in women with severe compared to mild prolapse (P < 0.05).

Conclusion

Increased expression of Bad, Bax, and decreased ratios of Bcl‐2/Bax, Bcl‐2/Bad suggest increased apoptotic activity or sensitivity to induction of apoptosis in vaginal tissues of women with POP. Neurourol. Urodynam. 30: 1627–1632, 2011. © 2011 Wiley Periodicals, Inc.
Bladder compliance what does it represent: Can we measure it, and is it clinically relevant?
Authors: Wyndaele J.J. , Gammie A. , Bruschini H. , De Wachter S. , Fry C.H. , Jabr R.I. , Kirschner‐Hermanns R. , Madersbacher H.
Published: June 2011

Aims

To report the conclusion of the Think Thank 8 on Compliance Discussions during the second ICI‐RS meeting in 2010.

Methods

During a 3‐day meeting a group of specialists discussed bladder compliance, what it represents, how it can be measured and if it is clinically relevant.

Results

Bladder compliance is the result of a mathematical calculation of the volume required for a unit rise of pressure measured during a cystometric filling. It gives an indication on how the different mechanisms in the bladder wall react on stretching. There is a need of standardization of measurement and suggestions for this are given in the text. Pitfalls are described and how to avoid them. There is a wide range of compliance values in healthy volunteers and groups of patients. Poor compliance needs to be defined better as it can have significant clinical consequences. Prevention and treatment are discussed.

Conclusion

If compliance is correctly measured and interpreted, it has importance in urodynamic testing and gives information relevant for clinical management. Neurourol. Urodynam. Neurourol. Urodynam. 30:714–722, 2011. © 2011 Wiley‐Liss, Inc.
Constructing trials to show whether urodynamic studies are necessary in lower urinary tract dysfunction
Authors: Bosch J. L. H. Ruud , Cardozo Linda , Hashim Hashim , Hilton Paul , Oelke Matthias , Robinson Dudley
Published: June 2011

Aims

This report reviews the evidence for the utility of urodynamic studies (UDS) in lower urinary tract dysfunction and tries to identify the necessity of constructing trials to show whether UDS are necessary.

Methods

An outline for a think tank discussion was prepared by the chairman of the session. Several experts selected relevant papers from a literature review of the Pubmed/Medline database (January 1966 to August 2010) and prepared a presentation of the evidence for the utility of UDS in the evaluation of several conditions, the prediction of treatment outcome, the prediction of complications and/or cost‐effectiveness. The following conditions were considered: urinary incontinence, symptoms suggestive of benign prostatic obstruction (LUTS/BPO), overactive bladder (OAB) and urogenital prolapse. Summary presentations were discussed by a large group of opinion leaders and experts and audio‐recorded. The proceedings of this process are the basis for this manuscript.

Results

The structured sessions resulted in detailed statements about the existing evidence for the utility of UDS in men after radical prostatectomy, men with uncomplicated LUTS/BPO, patients with OAB, female stress urinary incontinence (SUI) and urogenital prolapse.

Conclusions

UDS should be used for investigation of new treatment modalities and establishment of diagnoses whenever they are in doubt. UDS do not appear to be necessary before pelvic floor muscle training, medical treatment of LUTS/BPO or OAB, surgical treatment of primary female SUI or prolapse. RCT's with non‐inferiority design should be conducted to investigate UDS in patients before surgical treatment of the prostate, SUI or OAB. Neurourol. Urodynam. Neurourol. Urodynam. 30:735–740, 2011. © 2011 Wiley‐Liss, Inc.
Ultrasound imaging of the pelvic floor: Where are we going?
Authors: Tubaro Andrea , Koelbl Heinz , Laterza Rosa , Khullar Vik , de Nunzio Cosimo
Published: June 2011

We produced a non systematic review of ultrasound imaging of the pelvic floor in women with urinary incontinence (UI) and/or pelvic organ prolapse (POP).

We have searched the PubMed and Embase databases for the following PICO question: women; imaging; urinary incontinence, pelvic organ prolapse, pelvic floor, pelvic floor muscle, pelvic floor muscle training; physical examination, no imaging; diagnosis, prognosis, outcome. The production of a systematic review was deemed impossible based on the type and quality of the published evidence.

Clinical research focused on the pathophysiology of the UI and POP looking relation between anatomic abnormalities, childbirth, the risk of UI or POP, the outcome of conservative treatment and reconstructive surgery. Published papers fall into the remits of diagnostic studies but often fail to comply with the recommendations of the STARD initiative. Most published evidence remains the product of a single institution effort and confirmatory studies are rarely found. Imaging studies in patients with UI did not provide evidence of any clinical benefit in the management of patients. In patients with POP, interesting correlations have been identified such as between childbirth, dimension of levator hiatus, avulsion of levator ani and risk of prolapse, but the non clinical benefit of pelvic floor imaging could still not be identified.

Research on pelvic floor imaging requires a coordinated, international, multicentre effort to improve internal and external validity of imaging techniques, confirm observations published by single institutions and provide health technology assessment of imaging in the management of UI or POP patients. Neurourol. Urodynam. Neurourol. Urodynam. 30:729–734, 2011. © 2011 Wiley‐Liss, Inc.
Bladder outlet physiology in the context of lower urinary tract dysfunction
Authors: Sadananda Prajni , Vahabi Bahareh , Drake Marcus J.
Published: June 2011

Physiological function of the bladder outlet is complex and symptomatic consequences can result from outlet dysfunction. Within the outlet, smooth, and skeletal muscles constitute the contractile apparatus, but additional cell types include interstitial cells and neuroendocrine cells, and various transmitters are present in the innervation, raising the possibility of unrecognized functional subtleties. Key outlet functions are; maintained closure for urine storage, increased closure (guarding) during exertion, sustained opening for voiding, transient opening for territorial marking in animals and orthograde male ejaculation. These are co‐ordinated by several spinal and higher CNS centers, with overlap of the somatic, sympathetic and parasympathetic nervous systems. During voiding, urethral afferents may be important in maintaining detrusor contraction until completion of bladder emptying. Some of the bladder outlet afferents may be shared with the anal sphincter. Dysfunction of the outlet leads to conditions such as retrograde ejaculation, Fowler's syndrome, and detrusor sphincter dyssynergia. Urethral relaxation during urine storage may lead to urinary urgency, which may be misleadingly labeled as overactive bladder. Research priorities are numerous, including; peripheral cellular integrative physiology, interactions with other pelvic organs, interconnectivity of the CNS centers at all levels of the neuraxis, and standardized animal models of outlet functions such as reflex‐driven voiding. Neurourol. Urodynam. 30:708–713, 2011. © 2011 Wiley‐Liss, Inc.
Models for sensory neurons of dorsal root ganglia and stress urinary incontinence
Authors: Kakizaki Hidehiro , Kita Masafumi , Wada Naoki
Published: June 2011

Aims

To discuss (1) animal models for investigating bladder afferent pathways from the spinal cord to the brain and (2) animal models of stress urinary incontinence (SUI) with a special emphasis on functional and histopathological characteristics of each model.

Methods

Literature review of spinal mechanisms of bladder afferent pathways and animal models of SUI.

Results

Electrophysiological studies in the rat using pelvic nerve stimulation and recording of evoked potentials in the periaqueductal gray (PAG) prove to be a valuable tool to examine spinal mechanisms of bladder afferent pathways. Animal models of SUI in the rat include vaginal distention as simulated birth trauma, pudendal nerve crush or transection, urethral sphincter injury by electrocauterization, transabdominal urethrolysis, periurethral botulinum‐A toxin injection, and pubo‐urethral ligament transection. Functional and histopathological changes in the continence mechanism after injury are different between models.

Conclusions

Using animal models for sensory neurons, intrathecal and intravenous administration of certain drugs can be tested whether they affect the bladder afferent pathways from the spinal cord to the PAG. Animal models of SUI can serve as a tool to develop new pharmacologic therapies or periurethral injection therapies using stem cell implants. Neurourol. Urodynam. Neurourol. Urodynam. 30:653–657, 2011. © 2011 Wiley‐Liss, Inc.
What you don't know can hurt your community: Lessons from a local United Way
Authors: Carman Joanne G.
Published: June 2011

This paper describes how a controversial executive compensation package approved by a local United Way agency eclipsed the agency's long‐standing record and reputation of being a top fundraiser and pillar of the community. Using the framework developed by P. Connelly and York (2003), this case study illustrates how the lack of leadership and adaptive capacity within the board of directors, coupled with questions and speculation about managerial capacity, contributed to a highly visible scandal that resulted in the loss of the agency's chief executive officer, the resignation of the chairman of the board of directors, an internal investigation, and ultimately, a federal investigation. Not only did these events hurt the agency, which was forced to eliminate programs and cut staff, but these events hurt the annual campaign, which declined by more than 30 percent, resulting in substantial cuts in funding to dozens of nonprofit organizations. The findings from this study illustrate the importance of building strong governing boards that focus on both organizational processes and performance outcomes. They also highlight how important it is for the flagship charitable institutions to model best practices and invest in their own capacity.
Convergence of compact ADI method for solving linear Schrödinger equations
Authors: Liao Hong‐Lin , Sun Zhi‐Zhong , Shi Han‐Sheng , Wang Ting‐Chun
Published: June 2011

A compact ADI scheme of second‐order in time and fourth‐order in space is proposed for solving linear Schrödinger equations with periodic boundary conditions. By using the recently suggested discrete energy method, it is shown that the stable compact ADI method is unconditionally convergent in the maximum norm. Numerical experiments, including the comparisons with the second‐order ADI scheme and the time‐splitting Fourier pseudospectral method, are presented to support the theoretical results and show the effectiveness of our method. © 2011 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2012
Applicability of 2009 international consensus terminology and criteria for immune thrombocytopenia to a clinical pediatric population
Authors: Grace Rachael F. , Long Michelle , Kalish Leslie A. , Neufeld Ellis J.
Published: June 2011

Background

Since pediatric immune thrombocytopenia (ITP) is relatively infrequent, comparisons among clinical studies are critical but have previously been limited by differences in terminology. In 2009, an international working group (IWG) developed consensus criteria to enhance comparability in future studies in adults and children.

Methods

We performed a retrospective medical record review of all pediatric ITP patients seen at a single children's hospital with a first visit between 2003 and 2010 and applied both historical (criteriaHist) and IWG (criteriaIWG) ITP criteria to available clinical data.

Results

Among the 505 patients seen for ITP over 7 years, 98% could be classified as “acute” or “chronic” ITP using the criteriaHist, while only 90.7% could be classified as “newly diagnosed,” “persistent,” or “chronic” ITP using the criteriaIWG (P < 0.01). Only 33.7% met criteriaIWG for severe ITP, whereas 77.4% met criteriaHist for severe ITP. A striking difference was that overall response to therapies was lower if the criteriaIWG were used rather than the criteriaHist, particularly for IVIG (55.4% vs. 70%, P = 0.02) and rituximab (35.3% vs. 83.3% P = 0.05). Only 2 subjects (0.4%) met the criteriaIWG for refractory ITP.

Conclusions

Most ITP patients could easily be classified using the 2009 criteriaIWG. Limitations to applying the criteriaIWG included absence of treatment response durations, incomplete definition of pediatric “refractory ITP,” and exclusion of secondary ITP. Nevertheless, the criteriaIWG were more clinically relevant given the reliance on definitions based on bleeding and their ability to be applied prospectively. The utility of using the criteriaIWG within prospective trials remains to be determined. Pediatr Blood Cancer 2012; 58: 216–220. © 2011 Wiley Periodicals, Inc.
Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis
Authors: Zhizhuo Huang , Junmei Xu , Yuelin Shen , Qiang Qin , Chunyan Liu , Zhengde Xie , Kunling Shen
Published: June 2011

Background

This study aimed to investigate the prevalence of mutations in the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK in Chinese pediatric patients with EBV‐HLH.

Methods

Sixty‐seven pediatric patients diagnosed with EBV‐HLH in Beijing Children's Hospital were recruited. Nucleotide sequences of all exons and their flanking intronic sequences of PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK were amplified by PCR followed by direct sequencing.

Results

Eight patients were identified with heterozygous, compound heterozygous, or homozygous mutations in PFR1, UNC13D, and XIAP. Three missense mutations (c.83G>A, c.503G>A, c.632C>T) were found in PRF1 of two males and two females. Compound heterozygous c.93C>G and c.1066C>T were found in PRF1 of a 2.5‐year‐old female. Four different mutations were found in UNC13D of two patients: compound nonsense heterozygous mutations c.766C>T and c.1215C>G were found in one male and two splicing mutations c.1596+1G>C and c.2709+1G>A were found in another male. A heterozygous mutation c.1099+2T>C in XIAP was found in a 4‐year‐old male. No detrimental mutations were identified in STX11, SH2D1A, or ITK. NK cell activity did not differ between the eight FHL patients and the remaining patients. There was no statistical difference in clinical features and laboratory data for these two subgroups with biallelic and heterozygous mutations.

Conclusions

Seven novel mutations in PRF1, UNC13D, and XIAP were identified in EBV‐HLH patients. Only a fraction of the Chinese children with EBV‐HLH have genetic defects in PRF1, UNC13D, and XIAP. There were no gene mutations of PRF1/UNC13D/STX11/SH2D1A/XIAP/ITK in the majority of Chinese child patients with EBV‐HLH. Pediatr Blood Cancer 2012; 58: 410–414. © 2011 Wiley Periodicals, Inc.
Thirty‐day readmission rates following hospitalization for pediatric sickle cell crisis at freestanding children's hospitals: Risk factors and hospital variation
Authors: Sobota Amy , Graham Dionne A. , Neufeld Ellis J. , Heeney Matthew M.
Published: June 2011

Background

Readmission within 30 days after hospitalization for sickle cell crisis was developed by The National Association of Children's Hospitals (NACHRI) to improve hospital quality, however, there have been few studies validating this.

Procedure

We performed a retrospective examination of 12,104 hospitalizations for sickle crisis from July 1, 2006 and December 31, 2008 at 33 freestanding children's hospitals in the Pediatric Health Information System (PHIS) database. Hospitalizations met NACHRI criteria; inpatient admission, APR DRG code 662, age < 18, discharge home, and length of stay within 2 SD of the mean. We describe 30‐day readmission rates, identify factors associated with readmission accounting for patient‐level clustering and compare unadjusted versus adjusted variation in readmission rates.

Results

We identified 4,762 patients with 12,104 qualifying hospitalizations (1–30 per patient). Two thousand seventy‐four (17%) hospitalizations resulted in a readmission within 30 days. Significant factors associated with readmission were age (OR 1.06/year,P < 0.0001), inpatient use of steroids (OR 1.48,P = 0.01) admission for pain without other sickle complications (OR 1.52,P < 0.0001) and simple transfusion (OR 0.58,P = 0.0002). There was significant variation in readmission rates between hospitals, even after accounting for clustering by patient and hospital case mix.

Conclusions

In a sample of free‐standing children's hospitals, 17% of hospitalizations for sickle cell crisis result in readmission within 30 days. Older patients, those treated with steroids and those admitted for pain are more likely to be readmitted; simple transfusion is protective. Even after adjusting for case mix substantial hospital variation remains, but specific hospital to hospital comparisons differ depending on the exact methods used. Pediatr Blood Cancer 2012; 58: 61–65. © 2011 Wiley Periodicals, Inc.
A multidisciplinary paediatric diabetes health care team: perspectives on adolescent care
Authors: Spencer J , Cooper H
Published: June 2011

This paper focuses on a qualitative study of the experiences of a multidisciplinary health care team caring for adolescents with type 1 diabetes in a hospital in the North West of England.

It builds upon previous research which has explored the lived experiences of young people and their parents/guardians with the aim of better understanding blood glucose control in this age group.

Findings emphasise lack of human resources, the importance of effective team working, and the need for meaningful education which acknowledges adolescents' unique and complex social worlds.

Given these findings we are now developing a computer‐based ‘Adolescent Diabetes Needs Assessment Tool’ (ADNAT study), with a view to individualising self‐directed education and support. Copyright © 2011 John Wiley & Sons.
Education and training in paediatric diabetes: the UK position. Survey on behalf of the SWEET Project 2008–11
Authors: Waldron S , Allgrove J , Swift PGF
Published: June 2011

The aim of the three‐year SWEET Project EU was to establish Centres of Reference for Paediatric Diabetes in order to improve standards of care for children and young people (CYP) with diabetes across Europe. Part of this project involved making recommendations about education of CYP and their families, as well as of health care professionals (HCPs). The following UK data collected in 2009 contributed to the SWEET final data collection. Information covered diabetes education to CYP with diabetes, their families, staff in schools and HCPs. An online questionnaire was circulated to HCPs who were involved in the care of CYP with diabetes.

Responses from 100 HCPs were received, mainly from larger more specialised clinics and included all members of the multidisciplinary team (MDT). Results showed that few services have written comprehensive educational curricula for CYP; programmes of education are predominantly focused on education for insulin adjustment/carbohydrate counting protocols and pump therapy, with major deficiencies in psycho‐social interventions, family communication, continuing education and transition programmes. Learning outcomes are not adequately assessed and programmes are rarely linked to diabetes outcomes.

These deficiencies exist partly because paediatric diabetes has not been recognised or contracted as a specialty service. The majority of HCP posts in paediatric diabetes do not demand prior experience in the specialty. Standardised and accredited initial and continuing professional development opportunities are severely limited and often there is little support from NHS trusts. The functioning of MDTs could be improved through agreed team philosophies, consensus on targets and increased MDT ‘business meetings’. Respondents gave overwhelming support to the development of a National Paediatric Diabetes Framework that includes accredited, validated, structured education programmes for CYP, their families, schools and HCPs. Copyright © 2011 John Wiley & Sons.
Hypoglycaemia unawareness
Authors: Elliott J , Heller S
Published: June 2011

Hypoglycaemia unawareness can be a devastating complication in both types of diabetes. It is probably becoming more common as patients are urged to tighten their glycaemic control. The effects of improving glycaemic control on the background of increasing duration of diabetes are the main known risk factors for the condition. Antecedent hypoglycaemia diminishes physiological responses, and impairs the ability to identify further episodes, leading to a vicious downwards spiral and a high risk of further severe hypoglycaemic episodes. Fully established hypoglycaemia unawareness is thankfully rare, but difficulty in recognising the onset of hypoglycaemia is common. Therefore effective treatments to reverse or prevent hypoglycaemia unawareness are urgently needed.

This review article examines the evidence around the pathophysiology of hypoglycaemia unawareness, and current therapeutic strategies. Copyright © 2011 John Wiley & Sons.
Toughening of polylactide with natural rubber grafted with poly(butyl acrylate)
Authors: Zhang Chunmei , Man Changzhen , Pan Yonghao , Wang Weiwei , Jiang Long , Dan Yi
Published: June 2011

Natural rubber grafted with poly(butyl acrylate) (NR‐g‐PBA) in an attempt to toughen polylactide (PLA) was prepared by grafting butyl acrylate onto natural rubber (NR) through emulsion polymerization. The purified NR‐g‐PBA was confirmed by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. NR‐g‐PBA/PLA blend and NR/PLA blend were prepared with a Haake internal melt mixer. The morphology and mechanical properties of the blends were investigated as a function of rubber content. Observations by scanning electron microscopy showed that the spherical‐particle‐dispersed phase appearing in the NR/PLA blend was not found in the NR‐g‐PBA/PLA blend, which showed that NR grafted with PBA is compatible with PLA, and accounted for the efficient toughening effect on PLA. The elongation at break and the impact strength were significantly improved with an increase in NR‐g‐PBA content. The thermal stability of PLA decreased when blended with NR but was retained with NR‐g‐PBA. Copyright © 2011 Society of Chemical Industry
Universal screening for social–emotional competencies: A study of the reliability and validity of the DESSA‐mini
Authors: Naglieri Jack A. , LeBuffe Paul , Shapiro Valerie B.
Published: June 2011

The purpose of this study was to examine the reliability of the eight‐item Devereux Student Strengths Assessment (DESSA)‐mini and its validity in relation to the 72‐item version DESSA. The sample included teacher ratings for 1,234 children in kindergarten through eighth grade who comprised the standardization sample. The median alpha reliability coefficients across grades for the four forms of the DESSA‐mini ranged from a low of .915 (Mini 1) to a high of .924 (Mini 3). These findings suggested that DESSA‐minis have excellent reliability. The differences between the DESSA Social–Emotional Composite (SEC) T‐scores and T‐scores obtained from each of the four DESSA‐minis were trivial (the largest d‐ratio was .023). The percentage of times the DESSA‐mini and DESSA SEC T‐scores yielded the same result was computed (i.e., the score indicates or does not indicate whether the child needs social–emotional instruction). Those percentages ranged from a low of 94.8 (Mini 3) to a high of 96.5 (Mini 1). Finally, sensitivity, specificity, and positive and negative predictive power were examined for each DESSA‐mini. Findings suggested that the DESSA‐mini is a viable tool for universal screening of social–emotional competencies related to resilience. © 2011 Wiley Periodicals, Inc.
DNA affects the composition of lipoplex protein corona: A proteomics approach
Authors: Capriotti Anna L. , Caracciolo Giulio , Caruso Giuseppe , Foglia Patrizia , Pozzi Daniela , Samperi Roberto , Laganà Aldo
Published: June 2011

The distribution of drug delivery systems into the body is affected by plasma proteins adsorbed onto their surface. Furthermore, an exact understanding of the structure and morphology of drug carriers is fundamental to understand their role as gene delivery systems. In this work, the adsorption of human plasma proteins bound to cationic liposomes and to their relative DNA lipoplexes was compared. A shotgun proteomics approach based on HPLC coupled to high resolution MS was used for an efficient identification of proteins adsorbed onto liposome and lipoplex surfaces. The distinct pattern of proteins adsorbed helps to better understand the DNA compaction process. The experimental evidence leads us to hypothesize that polyanionic DNA is associated to the lipoplex surface and can interact with basic plasma proteins. Such a finding is in agreement with recent results showing that lipoplexes are multilamellar DNA/lipid domains partially decorated with DNA at their surface. Proteomics experiments showed that the lipoplex corona is rich of biologically relevant proteins such as fibronectin, histones and complement proteins. Our results provide novel insights to understand how lipoplexes activate the immune system and why they are rapidly cleared from the blood stream. The differences in the protein adsorption data detected in the presented experiments could be the basis for the establishment of a correlation between protein adsorption pattern and in vivo fate of intravenously administered nanoparticles and will require some consideration in the future.
Peptidome profiling of induced sputum by mesoporous silica beads and MALDI‐TOF MS for non‐invasive biomarker discovery of chronic inflammatory lung diseases
Authors: Terracciano Rosa , Preianò Mariaimmacolata , Palladino Grazia P. , Carpagnano Giovanna E. , Barbaro Maria P. Foschino , Pelaia Girolamo , Savino Rocco , Maselli Rosario
Published: June 2011

Induced sputum is recognized as being of increasing importance for the diagnosis and monitoring of chronic inflammatory lung diseases. The main purpose of this study is to provide a valid approach to better fractionate and characterize the still under‐estimated low‐molecular weight proteome of induced sputum by using mesoporous silica beads (MSBs) SPE coupled to MALDI‐TOF MS. Sputum peptides were captured from both derivatized and non‐derivatized MSBs and then profiled by MALDI‐TOF MS. Depending on the chemical groups present on the mesoporous surface, complex peptide mixtures were extracted from induced sputum and converted into reproducible MALDI profiles. The number of peaks detected as a function of S/N was evaluated for each mesoporous surface. More than 400 peaks with an S/N>5 were obtained in comparison to 200 peaks detected without MSBs. Additionally, as a proof‐of‐principle, we investigated the ability of this platform to discriminate between the “sputome” of patients with asthma and chronic obstructive pulmonary disease, and between these groups and those of healthy control subjects. Six m/z peaks emerged as potential diagnostic peptidic patterns able to differentiate these inflammatory airway diseases in the sputome range. Human α‐defensins (human neutrophil peptide (HNP)1, HNP2, HNP3) and three C‐terminal amidated peptides, one of which is phosphorylated on serine, were identified by MALDI‐TOF/TOF MS. These findings may contribute to defining a high‐throughput screening MS‐based platform for monitoring key peptidic‐biomarkers for inflammatory and chronic respiratory diseases in induced sputum samples.
Identification of cytochrome P450 2C2 protein complexes in mouse liver
Authors: Li Bin , Yau Peter , Kemper Byron
Published: June 2011

Interactions of microsomal cytochromes P450 (CYPs) with other proteins in the microsomal membrane are important for their function. In addition to their redox partners, CYPs have been reported to interact with other proteins not directly involved in their enzymatic function. In this study, proteins were identified that interact with CYP2C2 in vivo in mouse liver. Flag‐tagged CYP2C2 was expressed exogenously in mouse liver and was affinity purified, along with associated proteins which were identified by MS and confirmed by Western blotting. Over 20 proteins reproducibly copurified with CYP2C2. The heterogeneous sedimentation velocity of CYP2C2 and associated proteins by centrifugation in sucrose gradients and sequential immunoprecipitation analysis were consistent with multiple CYP2C2 complexes of differing composition. The abundance of CYPs and other drug metabolizing enzymes and NAD/NADP requiring enzymes associated with CYP2C2 suggest that complexes of these proteins may improve enzymatic efficiency or facilitate sequential metabolic steps. Chaperones, which may be important for maintaining CYP function, and reticulons, endoplasmic reticulum proteins that shape the morphology of the endoplasmic reticulum and are potential endoplasmic reticulum retention proteins for CYPs, were also associated with CYP2C2.
Global absolute quantification of a proteome: Challenges in the deployment of a QconCAT strategy
Authors: Brownridge Philip , Holman Stephen W. , Gaskell Simon J. , Grant Christopher M. , Harman Victoria M. , Hubbard Simon J. , Lanthaler Karin , Lawless Craig , O'cualain Ronan , Sims Paul , Watkins Rachel , Beynon Robert J.
Published: June 2011

In this paper, we discuss the challenge of large‐scale quantification of a proteome, referring to our programme that aims to define the absolute quantity, in copies per cell, of at least 4000 proteins in the yeast Saccharomyces cerevisiae. We have based our strategy on the well‐established method of stable isotope dilution, generating isotopically labelled peptides using QconCAT technology, in which artificial genes, encoding concatenations of tryptic fragments as surrogate quantification standards, are designed, synthesised de novo and expressed in bacteria using stable isotopically enriched media. A known quantity of QconCAT is then co‐digested with analyte proteins and the heavy:light isotopologues are analysed by mass spectrometry to yield absolute quantification. This workflow brings issues of optimal selection of quantotypic peptides, their assembly into QconCATs, expression, purification and deployment.
Functional analysis of novel phosphorylation sites of CREB‐binding protein using mass spectrometry and mammalian two‐hybrid assays
Authors: Xia Zanxian , Guo Mingquan , Ma Hong
Published: June 2011

In the Wnt/β‐catenin pathway, p300/CBP (CREB‐binding protein) is recruited by nuclear β‐catenin to regulate a wide array of T‐cell factor (TCF)‐dependent gene expression. Previous studies have indicated that CBP/β‐catenin complex‐mediated transcription is critical for cell proliferation. Both CBP and β‐catenin are phosphoproteins. The interaction domain has been mapped to the N‐terminal region of CBP (amino acids 1–111) and the C‐terminal region of β‐catenin, but it is unclear whether phosphorylation on specific residues of these regions is required for the interaction. To address this unmet challenge, phosphoproteomic profile of the critical N‐terminus of CBP was determined by utilizing TiO2 affinity chromatography followed by LC‐MS/MS analysis. Two unique and novel phosphorylation sites Ser77 and Ser92 were identified. Further studies aided by site‐directed mutagenesis, immunoprecipitation and mammalian two‐hybrid assay have concluded that the phosphorylation of a Proline‐directed Ser92 residue modulates the selective binding ability of CBP with β‐catenin. The specific Mitogen‐activated protein kinase inhibitor PD98059, which promotes cell cycle G1 arrest, concomitantly inhibits the interaction, and the evidences suggest that the MEK/ERK (extracellular signal‐regulated kinase) cascade activation is the upstream signal required for Ser92 phosphorylation, leading to enhancement of the interaction of CBP with β‐catenin.