Chromosome aberrations determined by sFISH and G-banding in lymphocytes from workers with internal deposits of plutonium

Purpose: To examine the influence of α-particle radiation exposure from internally deposited plutonium on chromosome aberration frequencies in peripheral blood lymphocytes of workers from the Sellafield nuclear facility, UK. Materials and methods: Chromosome aberration data from historical single colour fluorescence in situ hybridization (sFISH) and Giemsa banding (G-banding) analyses, together with more recent sFISH results, were assessed using common aberration analysis criteria and revised radiation dosimetry. The combined sFISH group comprised 29 men with a mean internal red bone marrow dose of 21.0 mGy and a mean external γ-ray dose of 541 mGy. The G-banding group comprised 23 men with a mean internal red bone marrow dose of 23.0 mGy and a mean external γ-ray dose of 315 mGy. Results: Observed translocation frequencies corresponded to expectations based on age and external γ-ray dose with no need to postulate a contribution from α-particle irradiation of the red bone marrow by internally deposited plutonium. Frequencies of stable cells with complex aberrations, including insertions, were similar to those in a group of controls and a group of workers with external radiation exposure only, who were studied concurrently. In a similar comparison there is some suggestion of an increase in cells with unstable complex aberrations and this may reflect recent direct exposure to circulating lymphocytes. Conclusions: Reference to in vitro dose response data for the induction of stable aberrant cells by α-particle irradiation indicates that the low red bone marrow α-particle radiation doses received by the Sellafield workers would not result in a discernible increase in translocations, thus supporting the in vivo findings. Therefore, the greater risk from occupational radiation exposure of the bone marrow resulting in viable chromosomally aberrant cells comes from, in general, much larger γ-ray exposure in comparison to α-particle exposure from plutonium.     

Clinical and neurophysiologic features of progressive myoclonus epilepsy without renal failure caused by SCARB2 mutations

Purpose: Mutations of the SCARB2 gene cause action myoclonus renal failure syndrome (AMRF), a rare condition that combines progressive myoclonus epilepsy (PME) with severe renal dysfunction. We describe the clinical and neurophysiologic features of PME associated with SCARB2 mutations without renal impairment. Methods: Clinical and neurophysiologic investigations, including wakefulness and sleep electroencephalography (EEG), polygraphic recording (with jerk‐locked back‐averaging and analysis of the EEG–EMG (electromyography) relationship by coherence spectra and phase calculation), multimodal evoked potentials, and electromyography were performed on five Italian patients with SCARB2 mutations. Key Findings: The main clinical features were adolescent–young adulthood onset, progressive action myoclonus, ataxia, absence of cognitive deterioration and, in most cases, epilepsy. The severity of the epilepsy could vary from uncontrolled seizures and status epilepticus in patients with adolescent onset to absent or rare seizures in patients with adult onset. Relevant neurophysiologic findings were a pronounced photosensitivity and massive action myoclonus associated with rhythmic myoclonic jerks at a frequency of 12–20 Hz, clinically resembling a postural tremor. The cortical origin of rhythmic myoclonus was demonstrated mainly by coherence and phase analysis of EEG–EMG signals indicating a significant EEG–EMG coupling and a direct corticospinal transfer. Significance: Our patients with SCARB2 mutations showed the clinical and neurophysiologic phenotype of PME, in which epilepsy could be extremely severe, extending the spectrum reported in the typical AMRF syndrome. Patients with PME of unknown origin of adolescent or young adult onset, with these neurophysiologic features, should be tested for SCARB2 mutations, even in the absence of renal impairment.     

Comparison of short-term antibiotic cover with a third-generation cephalosporin against conventional five-day therapy using metronidazole with an aminoglycoside in emergency and complicated colorectal surgery

In a prospective, randomized control trial, 152 consecutive patients requiring emergency or complicated colorectal surgery were allocated either to two doses of cefotetan or to five-day cover with gentamicin, and a single dose of metronidazole. Twenty-one patients received 6 gm of cefotetan before prolongation of prothrombin time dictated a change in the dose regimen such that all remaining patients (N = 55) received only 4 gm of cefotetan. The groups were well matched for diagnosis and surgical procedure. Rates of postoperative infection did not differ significantly between the groups, with wound infection rates occurring in 17 of 75 patients receiving gentamicin and metronidazole (22.7 percent) compared with ten of 75 receiving cefotetan (13 percent). Although wound infection rates were lower in the cefotetan group, the incidence of intra-abdominal abscess was similar in both groups. Eight patients receiving cefotetan developed intra-abdominal abscesses (11 percent), compared with seven receiving gentamicin and metronidazole (9 percent). Prolongation of prothrombin time in excess of 13 seconds occurred in six patients receiving cefotetan compared with no patients receiving gentamicin and metronidazole. None of these patients developed clinical bleeding, however.     

Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations

We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5‐associated malformations include bottom‐of‐the‐sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway. Ann Neurol 2014;75:782–787     

Interfacility transport of patients admitted to the ICU: perceived needs of family members

INTRODUCTION: Limited research has been published regarding the needs of immediate family members with respect to the transport of critically ill loved ones. Furthermore, very little information exists on transport teams members' perception of the needs of the family members. METHODS: During a 9-month period, a 25-item questionnaire was given to family members of adult patients who were transported by air or ground. All patients were admitted into an adult intensive care unit at a major university teaching hospital. Family members were asked to rank the relative importance of each item with regard to informational or situational needs. The identical questionnaire was given to the critical care transport teams employed by the hospital. The team members were asked to indicate what they thought the family members ranked as important. RESULTS: Forty-two of 100 family members (42%) returned the questionnaire by mail. All 13 (100%) critical care transport team members completed surveys as well. Statistical comparisons indicated that family members and team members differed significantly on 13 of 25 items. Team members generally underestimated the importance of these items to family members. CONCLUSION: These findings suggest that, in this sample, transporting crew members often misperceived family members informational and situational needs.     

Effects of repetitive loading on the growth‐induced changes in bone mass and cortical bone geometry: A 12‐month study in pre/peri‐ and postmenarcheal tennis players

Pre‐ and early puberty may be the most opportune time to strengthen the female skeleton, but there are few longitudinal data to support this claim. Competitive female premenarcheal (pre/peri, n = 13) and postmenarcheal (post, n = 32) tennis players aged 10 to 17 years were followed over 12 months. The osteogenic response to loading was studied by comparing the playing and nonplaying humeri for dual‐energy X‐ray absorptiometry (DXA) bone mineral content (BMC) and magnetic resonance imaging (MRI) total bone area (ToA), medullary area (MedA), cortical area (CoA), and muscle area (MCSA) at the humerus. Over 12 months, growth‐induced gains (nonplaying arm) in BMC, ToA, and CoA were greater in pre/peri (10% to 19%, p < .001) than in post (3% to 5%, p < .05 to .001) players. At baseline, BMC, ToA, CoA, and MCSA were 8% to 18% greater in the playing versus nonplaying arms in pre/peri and post players (all p < .001); MedA was smaller in the playing versus nonplaying arms in post only players (p < .05). When comparing the annual gains in the playing arm relative to changes in the nonplaying arm, the increases in ToA and CoA were greater in pre/peri than post players (all p < .05). The smaller the side‐to‐side differences in BMC and CoA at baseline, the larger the exercise benefits at 12 months (r = ?0.39 to ?0.48, p < .01). The exercise‐induced change in MCSA was predictive of the exercise benefits in BMC in pre/peri players only (p < .05). In conclusion, both pre/peri‐ and postmenarcheal tennis players showed significant exercise‐induced skeletal benefits within a year, with greater benefits in cortical bone geometry in pre/perimenarcheal girls. © 2011 American Society for Bone and Mineral Research.     

Increased radial glia quiescence,decreased reactivation upon injury and unaltered neuroblast behavior underlie decreased neurogenesis in the aging zebrafish telencephalon

The zebrafish has recently become a source of new data on the mechanisms of neural stem cell (NSC) maintenance and ongoing neurogenesis in adult brains. In this vertebrate, neurogenesis occurs at high levels in all ventricular regions of the brain, and brain injuries recover successfully, owing to the recruitment of radial glia, which function as NSCs. This new vertebrate model of adult neurogenesis is thus advancing our knowledge of the molecular cues in use for the activation of NSCs and fate of their progeny. Because the regenerative potential of somatic stem cells generally weakens with increasing age, it is important to assess the extent to which zebrafish NSC potential decreases or remains unaltered with age. We found that neurogenesis in the ventricular zone, in the olfactory bulb, and in a newly identified parenchymal zone of the telencephalon indeed declines as the fish ages and that oligodendrogenesis also declines. In the ventricular zone, the radial glial cell population remains largely unaltered morphologically but enters less frequently into the cell cycle and hence produces fewer neuroblasts. The neuroblasts themselves do not change their behavior with age and produce the same number of postmitotic neurons. Thus, decreased neurogenesis in the physiologically aging zebrafish brain is correlated with an increasing quiescence of radial glia. After injuries, radial glia in aged brains are reactivated, and the percentage of cell cycle entry is increased in the radial glia population. However, this reaction is far less pronounced than in younger animals, pointing to irreversible changes in aging zebrafish radial glia. J. Comp. Neurol. 521: 3099–3115, 2013. © 2013 Wiley Periodicals, Inc.     

A framework for evaluating image segmentation algorithms.

The purpose of this paper is to describe a framework for evaluating image segmentation algorithms. Image segmentation consists of object recognition and delineation. For evaluating segmentation methods, three factors-precision (reliability), accuracy (validity), and efficiency (viability)-need to be considered for both recognition and delineation. To assess precision, we need to choose a figure of merit, repeat segmentation considering all sources of variation, and determine variations in figure of merit via statistical analysis. It is impossible usually to establish true segmentation. Hence, to assess accuracy, we need to choose a surrogate of true segmentation and proceed as for precision. In determining accuracy, it may be important to consider different 'landmark' areas of the structure to be segmented depending on the application. To assess efficiency, both the computational and the user time required for algorithm training and for algorithm execution should be measured and analyzed. Precision, accuracy, and efficiency factors have an influence on one another. It is difficult to improve one factor without affecting others. Segmentation methods must be compared based on all three factors, as illustrated in an example wherein two methods are compared in a particular application domain. The weight given to each factor depends on application.