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OBJECTIVE Having a child diagnosed with cancer is distressing for parents. We aimed to compare worries and anxiety in parents of adult childhood cancer survivors with parents of the Swiss general population (GP-parents), and to evaluate characteristics associated with worry in parents of survivors. METHODS We conducted a nationwide, population-based study in parents of survivors (survivors aged ≥20 years at study, ≤16 years at diagnosis, >5 years post diagnosis) and GP-parents (≥1 child aged ≥20 years at study). We used the Worry and Anxiety Questionnaire (WAQ), and computed the WAQ total score (worries; possible range 0-80) and caseness for generalized anxiety disorder (anxiety), cognitive, somatic, and any criteria. We used multilevel, multivariable linear regression to identify characteristics associated with worries in parents of survivors. RESULTS We included 787 parents of 513 survivors (41.0% fathers) and 478 GP-parents (42.3% fathers). Parents of survivors and GP-parents did not differ regarding worries (16.6 vs. 17.1, p = .977), anxiety (2.7% vs. 3.6%, p = .536), cognitive (p = .440), and somatic criteria (p = .067). Less parents of survivors met any criteria (17.7% vs. 24.0%, p = .039). Half of parents reported current cancer-related worries. Higher cancer-related worries were reported by mothers (β = 4.1; 95% CI: 2.0-6.2), parents with one child (β = 5.9; 95% CI: 2.0-9.7), currently experiencing disadvantages because of their child's former disease (β = 7.3; 95% CI: 4.0-10.6), or with support needs (β = 9.0; 95% CI: 3.9-14.2; p = .001). CONCLUSIONS It is encouraging that most parents of adult survivors report similar worries and anxiety as GP-parents, but cancer-related worries are still prevalent. Efforts should be made to empower parents to seek psycho-social support if required.

Activation of AMPK has been associated with pro‐atrophic signaling in muscle. However, AMPK also has anti‐inflammatory effects, suggesting that in cachexia, a syndrome of inflammatory‐driven muscle wasting, AMPK activation could be beneficial. Here we show that the AMPK agonist AICAR suppresses IFNγ/TNFα‐induced atrophy, while the mitochondrial inhibitor metformin does not. IFNγ/TNFα impair mitochondrial oxidative respiration in myotubes and promote a metabolic shift to aerobic glycolysis, similarly to metformin. In contrast, AICAR partially restored metabolic function. The effects of AICAR were prevented by the AMPK inhibitor Compound C and were reproduced with A‐769662, a specific AMPK activator. AICAR and A‐769662 co‐treatment was found to be synergistic, suggesting that the anti‐cachectic effects of these drugs are mediated through AMPK activation. AICAR spared muscle mass in mouse models of cancer and LPS induced atrophy. Together, our findings suggest a dual function for AMPK during inflammation‐driven atrophy, wherein it can play a protective role when activated exogenously early in disease progression, but may contribute to anabolic suppression and atrophy when activated later through mitochondrial dysfunction and subsequent metabolic stress.

BACKGROUND Little is known about follow-up care attendance of adolescent survivors of childhood cancer, and which factors foster or hinder attendance. Attending follow-up care is especially important for adolescent survivors to allow for a successful transition into adult care. We aimed to (i) describe the proportion of adolescent survivors attending follow-up care; (ii) describe adolescents' health beliefs; and (iii) identify the association of health beliefs, demographic, and medical factors with follow-up care attendance. PROCEDURE Of 696 contacted adolescent survivors diagnosed with cancer at ≤16 years of age, ≥5 years after diagnosis, and aged 16-21 years at study, 465 (66.8%) completed the Swiss Childhood Cancer Survivor Study questionnaire. We assessed follow-up care attendance and health beliefs, and extracted demographic and medical information from the Swiss Childhood Cancer Registry. Cross-sectional data were analyzed using descriptive statistics and logistic regression models. RESULTS Overall, 56% of survivors reported attending follow-up care. Most survivors (80%) rated their susceptibility for late effects as low and believed that follow-up care may detect and prevent late effects (92%). Few (13%) believed that follow-up care is not necessary. Two health beliefs were associated with follow-up care attendance (perceived benefits: odds ratio [OR]: 1.56; 95% confidence interval [CI]: 1.07-2.27; perceived barriers: OR: 0.70; 95%CI: 0.50-1.00). CONCLUSIONS We show that health beliefs are associated with actual follow-up care attendance of adolescent survivors of childhood cancer. A successful model of health promotion in adolescent survivors should, therefore, highlight the benefits and address the barriers to keep adolescent survivors in follow-up care. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.

Busulfan (Bu) is an important component of the myeloablative conditioning regimen prior to hematopoietic stem cell transplantation (HSCT) especially in children. Intravenously administered Bu exhibits a therapeutic window phenomenon requiring therapeutic drug monitoring. Analytical methods developed for Bu routine monitoring were aimed at using low volumes of biological fluids and development of simple procedures to facilitate the dosage adjustment. In this report, we describe a simple, rapid method for Bu measurement using dried blood spots (DBS) from only 5 μL of whole blood.

TA-TMA is a pathology that occurs after allogenic HSC transplantation with an incidence of 4-13%, and represents one of the most severe vascular damage related with this therapy. We report here the case of a nine-yr-old girl suffering from a severe refractory aplastic anemia who received an unrelated, 9/10 HLA-matched HSC. Soon after transplantation, the patient developed a graft-versus-host disease (GvHD), a TA-TMA, and renal insufficiency. These pathologies remained refractory to the various treatments undertaken and required several hospitalizations in the intensive care unit. On day 106 post-HSC transfusion, after several episodes of intensive care, the patient was infused with mismatched, third-party MSCs. Schizocyte levels rapidly decreased after MSC infusion, and two wk later, most biological parameters returned to normal. Erythrocyte and thrombocyte transfusions were discontinued, and the patient remained stable for 10 wk. Thereafter, TA-TMA symptoms, viral reactivation, pleural and cardiac effusions reappeared and lead to the death of the patient. Our observations suggest that allogenic MSC infusion may decrease the symptoms of TA-TMA, but further investigation is required to determine how and when MSC should be infused to develop a long-lasting protective effect.

Summary Remarkable morphological diversity of virus-like par- ticles was observed by transmission electron micros- copy in a hypersaline water sample from Lake Retba, Senegal. The majority of particles morphologically resembled hyperthermophilic archaeal DNA viruses isolated from extreme geothermal environments. Some hypersaline viral morphotypes have not been previously observed in nature, and less than 1% of observed particles had a head-and-tail morphology, which is typical for bacterial DNA viruses. Culture- independent analysis of the microbial diversity in the sample suggested the dominance of extremely halophilic archaea. Few of the 16S sequences corre- sponded to known archeal genera (Haloquadratum, Halorubrum and Natronomonas), whereas the major- ity represented novel archaeal clades. Three sequences corresponded to a new basal lineage of the haloarchaea. Bacteria belonged to four major phyla, consistent with the known diversity in saline environments. Metagenomic sequencing of DNA from the purified virus-like particles revealed very few similarities to the NCBI non-redundant database at either the nucleotide or amino acid level. Some of the identifiable virus sequences were most similar to previously described haloarchaeal viruses, but no sequence similarities were found to archaeal viruses from extreme geothermal environments. A large pro- portion of the sequences had similarity to previously sequenced viral metagenomes from solar salterns.

The Antillean subspecies of the West Indian manatee Trichechus manatus is found throughout Central and South America and the Caribbean. Because of severe hunting pressure during the 17th through 19th centuries, only small populations of the once widespread aquatic mammal remain. Fortunately, protections in Belize reduced hunting in the 1930s and allowed the country’s manatee population to become the largest breeding population in the Wider Caribbean. However, increasing and emerging anthropogenic threats such as coastal development, pollution, watercraft collision and net entanglement represent challenges to this ecologically important population. To inform conservation and management decisions, a comprehensive molecular investigation of the genetic diversity, relatedness and population structure of the Belize manatee population was conducted using mitochondrial and microsatellite DNA. Compared with other mammal populations, a low degree of genetic diversity was detected (HE=0.455; NA=3.4), corresponding to the small population size and long-term exploitation. Manatees from the Belize City Cayes and Southern Lagoon system were genetically different, with microsatellite and mitochondrial FST values of 0.029 and 0.078, respectively (P ! 0.05). This, along with the distinct habitats and threats, indicates that separate protection of these two groups would best preserve the region’s diversity. The Belize population and Florida subspecies appear to be unrelated with microsatellite and mitochondrial FST values of 0.141 and 0.63, respectively (P ! 0.001), supporting the subspecies designations and suggesting low vagility throughout the northern Caribbean habitat. Further monitoring and protection may allow an increase in the Belize manatee genetic diversity and population size. A large and expanding Belize population could potential assist in the recovery of other threatened or functionally extinct Central American Antillean manatee populations.

Florida manatees ( Trichechus manatus latirostris ) are marine mammals that inhabit the coastal waters and rivers of the southeastern USA, primarily Florida. Previous studies have shown that Florida manatees have low mitochondrial DNA variability, suggesting that nuclear DNA loci are necessary for discriminatory analyses. Here we report 10 polymorphic microsatellite loci with an average of 4.2 alleles per locus, and average heterozygosity of 50.1%. These loci have been developed for use in population studies, parentage assignment, and individual identification.

It has been shown recently that the electrochemical reduction of carbon tetrachloride in N,N'-dimethylformamide follows a mechanism in which electron transfer and bond cleavage are concerted. We report here results concerning photoinduced electron transfer from the singlet excited state of two aromatic molecules, 2-ethyl-9,10-dimethoxyanthracene and perylene, to CCl4 , which is characterised by a quantum yield of complete quenching fragmentation ranging from 0.7 to 0.8. It is shown that a quantum yield below unity is compatible with a dissociative mechanism and arises from partitioning of the system at the intersection of the product- and ground-state potential energy surfaces. This phenomenon predominates over back electron transfer from the clustered fragments state. The photoinduced reductive cleavage of CCl4 thus provides a clear illustration of the recent theoretical prediction, that photoinduced dissociative electron transfers are not necessarily endowed with a unity quantum yield. This offers an opportunity to estimate the magnitude of the electronic matrix element that couples the fragmented product state and the ground reactant state.

The recording of chemosensory event-related potentials (CSERPs) has been established as an objective method in the assessment of central odor processing in humans. In the present study CSERPs were used to investigate whether human body odor is genetically determined by the major histocompatibility complex (MHC), referred to in humans as the human leukocyte antigen (HLA). The immunological function of the MHC is the discrimination of self/nonself within the immune system. In rodents it has been shown that body odor is significantly influenced by the MHC and that it can be discriminated by members of different species. To create a sufficiently large subject pool, 144 subjects were screened for their HLA class I loci A and B. During the electroencephalography (EEG) session the subjects (n= 40/20 women) were confronted with the body odor (axillary hair) of three different donors. Two donors (d1 and d2) were HLA-similar but had a different HLA type than the third donor (d3) and the perceiving subject. The third donor and the perceiver shared a similar HLA type. Half of the perceivers received odors from donors of the same sex, the other half smelt odors from donors of the opposite sex. In the EEG session subjects were presented with 200 trials. The odors were delivered through a constant flow olfactometer nonsynchronously to breathing. The odor of d1 appeared frequently (p= 0.6) whereas the odors of d2 and d3 appeared each at a rate of p= 0.2. During half the trials the subjects were instructed to respond to the odor of d2, during the other half to the odor of d3. The EEG was recorded from Fz, Cz, Pz, F3, P3, F4 and P4 in reference to linked mastoids. First results show that male perceivers show enhanced potentials in response to male donors of a similar HLA type (d3). The CSERP results of the other groups as well as valence and attractiveness ratings will be discussed.

Background: Cerebral injury can render meaningless an otherwise successful cardiac operation. As carbon dioxide management during hypothermic cardiopulmonary bypass has a major impact on cerebral blood flow during bypass, it may also influence postoperative cerebral function. The objective of this prospective, controlled, double-blind study was to compare the effect of pH-stat (temperature correction of blood gas analyses) or α-stat (no temperature correction) on brain function. Methods: Cerebral function was assessed non-invasively using neurological examination, a neuropsychological test battery, quantitative electroencephalogram and the cognitive evoked potential P300 preoperatively and on postoperative day 7 or 8. Forty-five patients undergoing elective aortocoro-nary bypass grafting in barbiturate/opiate anesthesia were randomised into a pH-stat- (n=23) and an α-stat-group (n=22). Membrane oxygenators with arterial line filtration and non-pulsatile flow at a perfussion pressure of 50–60 mmHg were used throughout. Results: One patient in each group developed a new paresis. Among 49 comparisons of cerebral function parameters, only 3 showed significant differences at the 5%-level, i.e. exactly what is expected purely by chance. These differences were too small to be clinically relevant and favored either pH-stat (theta-amplitude) or α-stat (subtest 3 of syndrome-short-test, number of mistakes in aiming). Conclusion: Under the bypass conditions of this study there was no difference in early cerebral functional outcome between pH- or α-stat carbon dioxide management during hypothermic cardiopulmonary bypass.

Eukaryotic translation initiation factor-4A (eIF-4A) plays a critical role in binding of eukaryotic mRNAs to ribosomes. It has been biochemically characterized as an RNA-dependent ATPase and RNA helicase and is a prototype for a growing family of putative RNA helicases termed the DEAD box family. It is required for mRNA-ribosome binding both in its free form and as a subunit of the cap binding protein complex, eIF-4F. To gain further understanding into the mechanism of action of eIF-4A in mRNA-ribosome binding, defective eIF-4A mutants were tested for their abilities to function in a dominant negative manner in a rabbit reticulocyte translation system. Several mutants were demonstrated to be potent inhibitors of translation. Addition of mutant eIF-4A to a rabbit reticulocyte translation system strongly inhibited translation of all mRNAs studied including those translated by a cap-independent internal initiation mechanism. Addition of eIF-4A or eIF-4F relieved inhibition of translation, but eIF-4F was six times more effective than eIF-4A, whereas eIF-4B or other translation factors failed to relieve the inhibition. Kinetic experiments demonstrated that mutant eIF-4A is defective in recycling through eIF-4F, thus explaining the dramatic inhibition of translation. Mutant eIF-4A proteins also inhibited eIF-4F-dependent, but not eIF-4A-dependent RNA helicase activity. Taken together these results suggest that eIF-4A functions primarily as a subunit of eIF-4F, and that singular eIF-4A is required to recycle through the complex during translation. Surprisingly, eIF-4F, which binds to the cap structure, appears to be also required for the translation of naturally uncapped mRNAs.

1. In four Java monkeys (Macaca fascicularis) 152 vestibular neurones were recorded in the parietal cortex located in the upper bank of the lateral sulcus near the posterior end of the insula. We called this region parieto-insular vestibular cortex (PIVC). PIVC extends about 6-8 mm in the anterior-posterior direction from the posterior part of the insula into the retroinsular region (stereotaxic co-ordinates: anterior 4-12 mm, lateral 16-19 mm and vertical 3-6 mm). 2. About two-thirds of the neurones recorded from this region responded to vestibular stimuli; the non-vestibular neurones responded predominantly to somatosensory stimulation of the neck and shoulder region. The PIVC area is a polysensory field, since almost all vestibular neurones were also activated by somatosensory and visual stimuli. Large-field optokinetic stimulation was the most effective visual stimulus. 3. With vestibular stimuli, responses to angular acceleration were dominant; steady tilt in darkness rarely led to any change in neuronal spontaneous activity. Of sixty-four neurones tested by rotation in more than one plane, fifty-four responded to excitation of semicircular canal receptors aroused by rotation in more than one of the three experimental planes (roll, yaw, pitch). Compared with vestibular brain stem units PIVC neurones discharged with a higher variability. 4. In the responses to horizontal rotation of the animal 38% type I, 53% type II and 9% type III units were recorded (classification according to Duensing & Schaefer, 1958). The gain measured with horizontal sinewave rotation was lower by a factor of about 4 in PIVC neurones as compared with the responses of vestibular neurones in the brain stem or thalamus (VPL). The phase response characteristics and the gain increase with increasing sinewave stimulus frequency, however, were in the same range as observed in neurones of the afferent vestibular system. 5. When the vestibular responses to sinusoidal rotation were tested in all three experimental planes (yaw, roll, pitch), the response strength as expressed by the amplitude of the peristimulus time histograms (PSTHs) differed for the three rotational planes. For different units the relative sensitivity to rotation in each of the three planes also differed. We concluded from this observation that different PIVC units had different optimum sensitivity planes for rotation with respect to the head co-ordinates, whereby all possible planes are represented.

1. One hundred and fifty-two vestibularly activated neurones were recorded in the parieto-insular vestibular cortex (PIVC) of four awake Java monkeys (Macaca fascicularis): sixty-two were tested systematically with visual stimulation and seventy-nine were tested with various somatosensory stimuli. With very few exceptions all vestibular neurones tested responded to visual and somatosensory stimulation, therefore being classified as polymodal vestibular units. 2. A most effective stimulus for all fifty-eight visually activated PIVC units was movement of a large structured visual pattern in an optimal direction. From forty-four units responsive to a horizontally moving optokinetic striped drum, twenty-nine were activated with optokinetic movement in the opposite direction to the activating vestibular stimulus ('synergistic' response), thirteen were activated optokinetically and vestibularly in the same direction ('antagonistic' responses) and two were biphasic. The gain of the optokinetic response to sinusoidal stimulation (average 0.28 (impulses s-1) (deg s-1)-1 at 0.2 Hz, 56 deg amplitude) was in a range similar to that of the vestibular gain at low frequencies. At 1 Hz some units only showed weak optokinetic responses or none at all, but the vestibular response was still strong. 3. With different 'conflicting' or 'enhancing' combinations of optokinetic and vestibular stimulation no generalized type of interaction was observed, but the responses varied from nearly 'algebraic' summation to no discernible changes in the vestibular responses by additional optokinetic stimuli. With all visual-vestibular stimulus combinations the responses to the vestibular stimulus remained dominant. 4. The optokinetic preferred direction was not related to gravitational coordinates since the optokinetic responses were related to the head co-ordinates and remained constant with respect to the head co-ordinates at different angles of steady tilt. 5. Almost all PIVC units were activated by somatosensory stimulation, whereby mainly pressure and/or movement of neck and shoulders (bilateral) and movement of the arm joints elicited vigorous responses. Fewer neurones were activated by lightly touching shoulders/arms or neck, by vibration and/or pressure to the vertebrae, pelvis and legs. 6. A most effective somatosensory stimulus was sinewave rotation of the body with head stationary. The gain of this directionally selective neck receptor response was in the range of vestibular stimulation. Interaction of vestibular and neck receptor stimulation was either of a cancellation or facilitation type.(ABSTRACT TRUNCATED AT 400 WORDS)

The identification of spatial and temporal patterns of soil properties and moisture structures is an important challenge in environmental and soil monitoring as well as for soil landscape model approaches. This work examines the use of hyperspectral remote sensing techniques for quantifying geophysical parameters from the hyperspectral reflectance of the vegetation canopy. These can be used as proxies of the underlying soil and soil water conditions. Different spectral index derivatives, single band reflectance, and spectral indices from the airborne hyperspectral sensor AISA were quantified and tested in univariate and multivariate regression models for their correlation with geophysical measurements with electromagnetic induction (EMI) and gamma-ray spectrometry. The best univariate models for predicting electrical conductivity based on spectral information were based on the vertical dipole of an EM38DD with an R 2 = 0.54 with the spectral index Normalized Pigments Reflectance Index (NPCI) as well as for the horizontal dipole of an EM38DD with an R 2 = 0.65 with the spectral index NPCI. For predicting soil characteristics measured with gamma-ray spectrometry we received the best model results for γTh with an R 2 = 0.55 with the spectral index NPCI and γK with an R 2 = 0.44 with the spectral index Triangular Vegetation Index (TVI) and NPCI. The combination of variables including the geographical elevation was tested as the input for a multivariate regression analysis. For EMI and gamma-ray measurements, the “elevation” was found to be the most predictive variable and an integration of spectral indices into the elevation-based model led to only a slight improvement in the predictive power for EMI. An improvement could be made to explain the variance of gamma-ray measurement signals by combining elevation and spectral information.