Differential magnification of rDNA gene types in bobbed mutants of Drosophila melanogaster

Summary In Drosophila melanogaster a partial loss of ribosomal genes leads to the bobbed phenotype. Magnification is a heritable increase in rDNA that may occur in males carrying a deleted X chromosome with a strong bobbed phenotype. The restriction patterns of X chromosome total rDNA, insertions and spacers from magnified bobbed strains were compared with those of the original bobbed mutations. It was found that magnification modifies restriction patterns and differentially affects gene types, increasing specific genes lacking insertions (INS^-). Increases in copy number of genes with type I insertions are generally lower than the total number of INS^- genes, while type II insertion genes are not perceptibly increased. The recovery of homogeneous progeny from a single premagnified male indicates that the magnification event might take place and become stable very early in the germ line, arguing against magnification being due to extrachromosomal amplification. Additionally, some gene types increase 3.5-fold while others are eliminated, indicating that they could not result from a single unequal cross-over. These results are in good agreement with the existence of partial clustering of rDNA genes according to type, and suggest that magnification could result from local amplification of genes.     

A Monte Carlo study of the influence of focal spot size,intensity distribution,breast thickness and magnification on spatial resolution of an a-Se digital mammography system using the generalized MTF

In this study the generalized Modulation Transfer Function (GMTF) and the geometric sharpness (S_geo) were used (i) to study the effects of various focal spot sizes (0.04 mm–0.3 mm), x-ray intensity distributions (Gaussian and double Gaussian), breast thicknesses (2–7 cm) and magnifications M (1.0–2.0) on the spatial resolution of an a-Se digital mammography system, (ii) to identify suitable focal spots for magnification mammography and (iii) derive optimum magnifications. For the calculation of GMTF the required components were: focal spot MTF, obtained from theory, detector MTF, scatter MTF and scatter fraction obtained from Monte Carlo simulations. The results showed that focal spots with sizes up to 0.18 mm are suitable for magnification mammography offering a GMTF which is >50% and >20% at the respective object frequencies of 6.5 mm⁻¹ and 9 mm⁻¹. Focal spots with sizes < 0.16 mm and Gaussian. intensity distribution, or sizes ≤ 0.1 mm and double Gaussian, offer a system resolution which improves or does not deteriorate with magnification for most object frequencies. For larger focal spots, i.e. 0.16–0.18 mm for a Gaussian and 0.12–0.18 mm for a double Gaussian. intensity distribution, optimum magnifications exist which depend on the object frequency and breast thickness. System resolution (in terms of S_geo) is maximized at M = 1.8–2.0 (all breast thicknesses) for Gaussian intensity distribution, and at M = 1.4–1.6 (breast thicknesses ≤ 4 cm) and M = 1.6–1.8 (thicker breasts) for double Gaussian.     

Micra leadless pacemaker retrieval in a pediatric patient

We present a case of a 13-year old patient with partially reversibly post-operative heart block who underwent leadless pacemaker placement. After post-anesthesia wretching/gagging episode she developed device microdislodgement and increased/intolerable capture thresholds. The device was removed and another placed with adequate thresholds for good longevity.     

Replacing lectures by textbased flexible learning: students' performance and perceptions

This paper presents the results of an extended evaluation programme designed to test the effectiveness of text-based flexible learning as a replacement to 30 – 50% of the lectures in certain modules in conventional undergraduate courses within the School of Life Sciences at Napier University. For examinations in which students answered both types of question, marks for questions based on topics taught by flexible learning were equivalent to marks for questions based on topics taught by conventional teaching methods. Marks for examinations in which at least 50% of the answers were based on topics taught by flexible learning were equivalent to marks for examinations in which questions were based on topics taught by conventional teaching methods. Rates of achievement of a mark of 40% or more at first attempt for examinations in which at least 50% of the answers were based on topics taught by flexible learning were significantly better than rates of achievement of a mark of 40% or more at first attempt for questions based on topics taught by conventional teaching methods. Students gave positive feedback on flexible learning, both verbally and by questionnaire, and showed highly significant bias in favour of topics taught by flexible learning in their choice of questions in examinations. The flexible learning programme studied here has satisfied the various quality assurance criteria in place within the University throughout the time that it has been in operation. The evaluation has demonstrated that the textbased flexible learning programme studied here was an effective alternative to lectures.     

Temporal and geospatial trends of pediatric cancer incidence in Nebraska over a 24-year period

BackgroundData from the Surveillance, Epidemiology, and End Results (SEER) revealed that the incidence of pediatric cancer in Nebraska exceeded the national average during 2009–2013. Further investigation could help understand these patterns.MethodsThis retrospective cohort study investigated pediatric cancer (0–19 years old) age adjusted incidence rates (AAR) in Nebraska using the Nebraska Cancer Registry. SEER AARs were also calculated as a proxy for pediatric cancer incidence in the United States (1990–2013) and compared to the Nebraska data. Geographic Information System (GIS) mapping was also used to display the spatial distribution of cancer in Nebraska at the county level. Finally, location–allocation analysis (LAA) was performed to identify a site for the placement of a medical center to best accommodate rural pediatric cancer cases.ResultsThe AAR of pediatric cancers was 173.3 per 1,000,000 in Nebraska compared to 167.1 per 1,000,000 in SEER. The AAR for lymphoma was significantly higher in Nebraska (28.1 vs. 24.6 per 1,000,000; p = 0.009). For the 15–19 age group, the AAR for the 3 most common pediatric cancers were higher in Nebraska (p < 0.05). Twenty-three counties located >2 h driving distance to care facilities showed at least a 10% higher incidence than the overall state AAR. GIS mapping identified a second potential treatment site that would alleviate this geographic burden.ConclusionsRegional differences within Nebraska present a challenge for rural populations. Novel use of GIS mapping to highlight regional differences and identify solutions for access to care issues could be used by similar states.     

Ventricular tachycardia in the setting of a large cardiac fibroma in a pediatric patient

Ventricular tachycardia and cardiac tumors are both extremely rare diagnoses in pediatric patients. We report a pediatric case of cardiac fibroma that was noted during the work up of ventricular tachycardia in a young patient concomitantly diagnosed with severe acute respiratory syndrome coronavirus 2.     

Diagnostic dilemma of cardiac syncope in pediatric patients

Aims

Syncope is defined as temporary loss of consciousness and postural tone resulting from an abrupt transient decrease in cerebral blood flow. The present work aimed at determining how diagnostic tests are used in the evaluation of pediatric syncope at a tertiary pediatric referral center and to report on the utility and the yield of these tests.

Settings and Design

Retrospective study conducted at a tertiary referral arrhythmolology service

Methods and Material

The clinical charts of 234 pediatric patients presenting with a primary complaint of syncope with an average age of 7.48 ± 3.82(3.5-16) years were reviewed by the investigators.

Statistical analysis used

Statistical Package of social science (SPSS) version 9,0 was used for analysis of data.

Results

The commonest trigger for syncope in the study population was early following exercise (n=65) and the commonest prodrome was palpitation, noted in 25 patients. A murmur was present in 19 of our patients (8.3%) while 10.7% (n=25) had abnormal ECGs. Of the 106 echocardiograms done, 14 (13.2%) were abnormal. Only two of them were missed by ECG. All patients were offered ambulatory 24 hour ECG. One patient with sick sinus syndrome was diagnosed only with Holter.

Conclusions

Clues to the presence of cardiac syncope may include acute onset of syncope, frequent episodes, low difference between blood pressure readings in supine and erect positions (after standing for 2 minutes) and most importantly an abnormal 12 lead ECG. Transthoracic echo and Holter monitoring have low yield in pediatric syncope.     

Applications of the molecular dynamics flexible fitting method

In recent years, cryo-electron microscopy (cryo-EM) has established itself as a key method in structural biology, permitting the structural characterization of large biomolecular complexes in various functional states. The data obtained through single-particle cryo-EM has recently seen a leap in resolution thanks to landmark advances in experimental and computational techniques, resulting in sub-nanometer resolution structures being obtained routinely. The remaining gap between these data and revealing the mechanisms of molecular function can be closed through hybrid modeling tools that incorporate known atomic structures into the cryo-EM data. One such tool, molecular dynamics flexible fitting (MDFF), uses molecular dynamics simulations to combine structures from X-ray crystallography with cryo-EM density maps to derive atomic models of large biomolecular complexes. The structures furnished by MDFF can be used subsequently in computational investigations aimed at revealing the dynamics of the complexes under study. In the present work, recent applications of MDFF are presented, including the interpretation of cryo-EM data of the ribosome at different stages of translation and the structure of a membrane-curvature-inducing photosynthetic complex.     

A simple and flexible Holm gatekeeping procedure

Major objectives of a clinical trial are commonly stated in a hierarchical order as primary and secondary. The parallel gatekeeping testing strategy provides an opportunity to assess secondary objectives when all or partial primary objectives are achieved. The current available gatekeeping procedures have different pros and cons so users either need to justify the assumption associated with some procedures or tolerate suboptimal power performance of other procedures. By applying the Holm test with a flexible alpha splitting technique, we propose a procedure which (1) is powerful for assessing the primary objectives, (2) can be used when no assumption can be made on the dependency structure of test statistics, and (3) has the full flexibility to allocate user-preferred alpha to assess the secondary objectives based on the number of primary objectives achieved. A real clinical trial example is used for illustration of the proposed procedure.     

Intellectual functioning and multi-dimensional attentional processes in long-term survivors of a central nervous system related pediatric malignancy

Aims

Central nervous system (CNS) malignancies and/or their treatment in pediatric cancer survivors are known to be associated with deficits in neuropsychological functions. We report findings from a nation-wide study of childhood cancer survivors to investigate intelligence and attention/concentration from a multi-dimensional perspective in a diverse sample from this population.

Main methods

Four hundred forty-four pediatric cancer survivors between 6 and 17 years of age, who had suffered CNS involvement associated with their malignancy, were evaluated. All patients completed a measure of general intelligence. Attention was measured by a continuous performance test (CPT) and by parental report using a standardized psychological inventory.

Key findings

Social economic status (SES) was a significant predictor of intellectual functioning and scores on independent measures of attention. After controlling for SES, cranial radiation therapy (CRT) was strongly predictive of impairments in intellectual functioning. Patients who had completed a transplant procedure did not have significant impairments in intellectual functioning when compared to other participants. CPT performance was most clearly influenced by a younger age at diagnosis and the presence of a supratentorial brain tumor. Reaction time was lower in patients who had received CRT. Gender did not correlate with CPT performance, but caregiver reports of deficits in attentional functioning were more prevalent in girls compared to boys.

Significance

These findings are important given the large, representative sample and multi-dimensional assessment of attentional functioning. The presence of a very strong SES effect on all dependent variables must be addressed in studies of this nature.     

Oxidative stress biomarkers in pediatric sepsis: a prospective observational pilot study

Objectives: Oxidative stress is known to participate in the progression of sepsis. Definite data regarding the behavior of oxidative stress biomarkers in pediatric sepsis is still lacking. This study hypothesized that oxidative stress occurs in pediatric sepsis and that the magnitude of the redox derangement is associated with worse clinical progression.

Methods: Forty-two previously healthy pediatric patients with sepsis and a group of control subjects were included. Oxidative stress and inflammatory activity biomarkers were determined in blood samples. Patients were prospectively followed until their discharge or death.

Results: Patients with non-severe and severe sepsis showed higher levels of plasmatic antioxidant capacity, lower erythrocyte thiol index, lower superoxide dismutase and catalase activities, higher glutathione peroxidase activity, and higher plasmatic F₂-isoprostanes concentration than controls. Patients with severe sepsis had higher NF-kappaB activation than those with non-severe sepsis. Although we observed changes in some biomarkers in patients with worse clinical evolution, the explored biomarkers did not correlate with clinical estimators of outcome.

Discussion: Oxidative stress occurs in pediatric sepsis, resulting in oxidative damage. The explored biomarkers are not useful as outcome predictors in the studied population. The behavior of these biomarkers still needs to be addressed in broader groups of pediatric patients with sepsis.     

A mechanically strong, flexible and conductive film based on bacterial cellulose/graphene nanocomposite

A highly flexible nanocomposite film of bacterial cellulose (BC) and graphene oxide (GO) with a layered structure was presented using the vacuum-assisted self-assembly technique. Microscopic and X-ray diffraction measurements demonstrated that the GO nanosheets were uniformly dispersed in the BC matrix. The interactions between BC and GO were studied by Fourier transformation infrared spectroscopy. Compared with pristine BC, the integration of 5 wt% GO resulted in 10% and 20% increase in Young's modulus and tensile strength of the composite film. The electrical conductivity of the composite film containing 1 wt% GO after in situ reduction showed a remarkable increase by 6 orders of magnitude compared with the insulated BC.     

Electromyography responses of pediatric and young adult volunteers in low-speed frontal impacts

No electromyography (EMG) responses data exist of children exposed to dynamic impacts similar to automotive crashes, thereby, limiting active musculature representation in computational occupant biomechanics models. This study measured the surface EMG responses of three neck, one torso and one lower extremity muscles during low-speed frontal impact sled tests (average maximum acceleration: 3.8 g; rise time: 58.2 ms) performed on seated, restrained pediatric (n = 11, 8–14 years) and young adult (n = 9, 18–30 years) male subjects. The timing and magnitude of the EMG responses were compared between the two age groups. Two normalization techniques were separately implemented and evaluated: maximum voluntary EMG (MVE) and neck cross-sectional area (CSA). The MVE-normalized EMG data indicated a positive correlation with age in the rectus femoris for EMG latency; there was no correlation with age for peak EMG amplitudes for the evaluated muscles. The cervical paraspinous exhibited shorter latencies compared with the other muscles (2–143 ms). Overall, the erector spinae and rectus femoris peak amplitudes were relatively small. Neck CSA-normalized peak EMG amplitudes negatively correlated with age for the cervical paraspinous and sternocleidomastoid. These data can be useful to incorporate active musculature in computational models, though it may not need to be age-specific in low-speed loading environments.     

Assisted reproductive technology and the risk of pediatric cancer: A population based study and a systematic review and meta analysis

BackgroundThere is controversy whether exposure to assisted reproductive technology (ART) is associated with increased risk of pediatric cancer.We aimed at calculating the overall risk of pediatric cancers after ART in a large cohort of exposed women; and to conduct a systematic review and meta- analysis of cohort studies examining overall risk of pediatric cancers after ART.MethodsAll children born in Israel who were members of Maccabi Health Services (MHS) between 1999 and 2016 after ART, were linked to the Israeli Registry of Childhood Cancer (IGS) to identify those with cancer diagnosed before 16 years of age. In parallel we conducted a systematic review and meta-analysis of observational cohort studies with more than 5000 ART- exposed cases that measured pediatric cancer after ART.ResultsIn the cohort study, the risk ratio for pediatric cancer after ART in general was 0.95 (95% CI, 0.76–1.19). The RR was 1.09 (95% CI, 0.79–1.48) for IVF treatments. Meta- analysis of 13 cohort studies with a total of 750,138 women exposed to ART (with 1152 pediatric cancers) and 214,008,000 unexposed controls (with 30,458 pediatric cancers) did not reveal increased risk for pediatric cancers (RR 0.99; 95% CI, 0.85–1.15).ConclusionsBased on very large numbers, ART in general, and IVF in particular, are not associated with overall increased risk of pediatric cancer.     

The response of the pediatric head to impacts onto a rigid surface

The study of pediatric head injury relies heavily on the use of finite element models and child anthropomorphic test devices (ATDs). However, these tools, in the context of pediatric head injury, have yet to be validated due to a paucity of pediatric head response data. The goal of this study is to investigate the response and injury tolerance of the pediatric head to impact.Twelve pediatric heads were impacted in a series of drop tests. The heads were dropped onto five impact locations (forehead, occiput, vertex and right and left parietal) from drop heights of 15 and 30 cm. The head could freely fall without rotation onto a flat 19 mm thick platen. The impact force was measured using a 3-axis piezoelectric load cell attached to the platen.Age and drop height were found to be significant factors in the impact response of the pediatric head. The head acceleration (14%–15 cm; 103–30 cm), Head Injury Criterion (HIC) (253%–15 cm; 154%–30 cm) and impact stiffness (5800%–15 cm; 3755%–30 cm) when averaged across all impact locations increased with age from 33 weeks gestation to 16 years, while the pulse duration (66%–15 cm; 53%–30 cm) decreased with age. Increases in head acceleration, HIC and impact stiffness were also observed with increased drop height, while pulse duration decreased with increased drop height.One important observation was that three of the four cadaveric heads between the ages of 5-months and 22-months sustained fractures from the 15 cm and 30 cm drop heights. The 5-month-old sustained a right parietal linear fracture while the 11- and 22-month-old sustained diastatic linear fractures.     

放大染色内镜对结节性胃炎、胃粘膜相关组织淋巴瘤的诊断

目的：探讨放大染色内镜对结节性胃炎、胃粘膜相关组织淋巴瘤诊断的可行性。方法：选择哈尔滨医科大学第四临床医学院2007年5月～2010年7月诊断的结节性胃炎、疑诊胃粘膜相关组织淋巴瘤患者,观察临床、内镜、病理表现、幽门螺杆菌感染情况和根除治疗的效果。并应用日本FUJINONEG-590ZW型放大内镜对患者进行检查,观察根除幽门螺杆菌前后结节性胃炎、胃粘膜相关组织淋巴瘤的改变。结果：纳入分析的100例成人患者,男25例,女75例,年龄19-68岁,平均年龄39．2岁。主要临床表现为上腹痛和消化不良症状。内镜下表现为胃窦部为主,可扩展至胃体部的色泽均匀的结节样或颗粒样改变。病理检查显示胃窦部活检标本中有伴生发中心的淋巴滤泡增生。所有患者均有幽门螺杆菌感染,经根除治疗后,症状缓解率达92．0％。结论：结节性胃炎、胃粘膜相关组织淋巴瘤发生与幽门螺杆菌感染相关,放大染色内镜对结节性胃炎有诊断意义。     

Image quality comparison of a nonlinear image-based noise reduction technique with a hybrid-type iterative reconstruction for pediatric computed tomography

PurposeTo compare computed tomography (CT) image properties between a vendor-independent image-based noise reduction technique, Image-space Noise Reduction (iNoir) and a hybrid-type iterative reconstruction technique, Adaptive Statistical Iterative Reconstruction (ASIR).MethodsA cylindrical water phantom, corresponding to pediatric body size, containing soft-tissue-equivalent rod and 12-mg iodine/ml rod was scanned at size-specific dose estimates of 8.4 and 16.7 mGy. For assessments of image quality and noise texture change, task-based system performance function (SPF) and peak frequency difference (PFD) were compared, respectively, among filtered back projection (FBP), IR image with 50%-blending rate (50%ASIR), 100%ASIR, 50%iNoir, and 100%iNoir. Human observer test for pediatric CT images was performed by radiologists.ResultsFor the soft-tissue contrast, SPF² of 100%iNoir was the highest. The average SPF² between 0.1 and 0.5 cycles/mm for 100%iNoir increased by approximately 70% compared with FBP, while ASIR indicted slight increases in the frequency region of >0.2 cycles/mm. For the iodine contrast, 100%iNoir indicated highest values at the spatial frequencies corresponding pediatric artery diameters. The PFDs of iNoir were negligible and lower than that of ASIR. The results of human observer test supported results of SPF² and PFD.ConclusionsCompared with ASIR, iNoir provided better image quality for pediatric abdominal CT without compromising noise texture change.     

Combined approaches to flexible fitting and assessment in virus capsids undergoing conformational change

Fitting of atomic components into electron cryo-microscopy (cryoEM) density maps is routinely used to understand the structure and function of macromolecular machines. Many fitting methods have been developed, but a standard protocol for successful fitting and assessment of fitted models has yet to be agreed upon among the experts in the field. Here, we created and tested a protocol that highlights important issues related to homology modelling, density map segmentation, rigid and flexible fitting, as well as the assessment of fits. As part of it, we use two different flexible fitting methods (Flex-EM and iMODfit) and demonstrate how combining the analysis of multiple fits and model assessment could result in an improved model. The protocol is applied to the case of the mature and empty capsids of Coxsackievirus A7 (CAV7) by flexibly fitting homology models into the corresponding cryoEM density maps at 8.2 and 6.1 Å resolution. As a result, and due to the improved homology models (derived from recently solved crystal structures of a close homolog – EV71 capsid – in mature and empty forms), the final models present an improvement over previously published models. In close agreement with the capsid expansion observed in the EV71 structures, the new CAV7 models reveal that the expansion is accompanied by ∼5° counterclockwise rotation of the asymmetric unit, predominantly contributed by the capsid protein VP1. The protocol could be applied not only to viral capsids but also to many other complexes characterised by a combination of atomic structure modelling and cryoEM density fitting.