Cryopreservation of Winter-dormant Apple Buds IV: Critical Temperature Variation that Can Compromise Survival.

BACKGROUND: Precise temperature control in several key areas during cryopreservation of dormant, winter apple buds is critical for maximal survival. OBJECTIVE: To consider the effects of pre-harvest temperature, the duration of incubation at -30°C and variation in rewarming rate on survival. MATERIALS AND METHODS: Dormant winter buds of Malus x domestica cultivars were harvested with two different acclimation histories and cryopreserved with variation in incubation time at -30°C. Recovery from LN using slow, intermediate and rapid rewarming was investigated as well as preservation after prolonged storage at -4°C. RESULTS: The effects on survival of preharvest temperature regime and an altered -30°C incubation regime are cultivar dependent and an increase in rewarming rate has a strong negative effect on recovery. CONCLUSION: Post-thaw survival of the winter-dormant buds can be compromised by increased temperature over a period as short as 5 days prior to bud harvest. Varying incubation times at -30°C produce variable, cultivar dependent, survival and moderate increases in rewarming rates can also radically reduce survival.

[Kyphoplasty combined with intraoperative radiotherapy (Kypho-IORT). Alternative therapy for patients with oligometastatic spinal metastases]. / Kyphoplastie kombiniert mit intraoperativer Radiotherapie (Kypho-IORT). Therapiealternative für den oligometastasierten Patienten mit Wirbelsäulenmetastasen.

BACKGROUND: Due to a more effective systemic therapy the survival of patients suffering from malignant tumors has been significantly improved but a longer life span is often associated with a higher incidence of osseous metastases. The majority of these metastases are localized in the spine causing pain, instability and neurological impairments. The interdisciplinary management of spinal metastases previously consisted of stabilization followed by fractionated external body radiation therapy. A reduction in procedural severity and morbidity as well as consideration of self-sufficiency and hospitalization time are important target parameters for these palliative patients. METHOD AND RESULTS: Kyphoplasty combined with intraoperative radiotherapy (Kypho-IORT) is one of several modern treatment options, which involves a minimally invasive procedure with local high-dose transpedicular irradiation of the spine with low-energy (50 kV) X-rays. Immediately following irradiation, stabilization of the spine is carried out using kyphoplasty via the same access route so that a single stage procedure with excellent pain reduction and good local tumor control can be achieved. This article presents clinical data for this procedure and the different fields of indications are critically reviewed and compared to other therapy options. Methodological improvements and options for further individualization of therapy are demonstrated. CONCLUSION: The Kypho-IORT procedure is a safe, feasible and beneficial modern treatment option for instant stabilization and local tumor control in patients with spinal metastases. More than 100 operations have been successfully performed so that the method can be deemed suitable for inclusion in the clinical routine. A phase II dose escalation study has now been completed and submitted for publication and a 2-arm non-inferiority trial (phase III study) for comparison with conventional irradiation is in progress.

A large-scale, rapid public health response to rabies in an organ recipient and the previously undiagnosed organ donor.

This article describes and contrasts the public health response to two human rabies cases: one organ recipient diagnosed within days of symptom onset and the transplant donor who was diagnosed 18 months post-symptom onset. In response to an organ-transplant-related rabies case diagnosed in 2013, organ donor and recipient investigations were conducted by multiple public health agencies. Persons with potential exposure to infectious patient materials were assessed for rabies virus exposure. An exposure investigation was conducted to determine the source of the organ donor's infection. Over 100 persons from more than 20 agencies spent over 2700 h conducting contact investigations in healthcare, military and community settings. The 564 persons assessed include 417 healthcare workers [5.8% recommended for post-exposure prophylaxis (PEP)], 96 community contacts (15.6% recommended for PEP), 30 autopsy personnel (50% recommended for PEP), and 21 other persons (4.8% recommended for PEP). Donor contacts represented 188 assessed with 20.2% recommended for PEP, compared with 5.6% of 306 recipient contacts recommended for PEP. Human rabies cases result in substantial use of public health and medical resources, especially when diagnosis is delayed. Although rare, clinicians should consider rabies in cases of encephalitis of unexplained aetiology, particularly for cases that may result in organ donation.

A virtual source model of a kilo-voltage radiotherapy device.

The purpose of this work is to develop a virtual source model (VSM) for the 50 kV INTRABEAM® device for Monte Carlo (MC) dose calculation. The geometry of the device was modelled in Geant4. A phase space file (PSF) was computed by simulating the interactions of monoenergetic primary electrons with the target. The PSF was approximated by computing the energy spectrum of the photons in the PSF. The variation of photon intensity, mean direction cosine and standard deviation along the axis of the source was thereafter computed. The isotropy of the source was used to approximate the properties of the source on the transverse plane. These functional approximations thereafter defined the VSM of the device. A sub-source was used to account for two kinds of photons, which were suppressed by the PSF approximation method. The intensity (relative to the main source) and emission directions of the sub-source required optimization. Optimization was achieved by the iterative adjustment of either or both parameters following MC simulation with the VSM and comparison of the calculated results to experimental data. The optimized source model was validated by comparing the calculated dose to water under several experimental setups, with reference data from the manufacturer, independent dosimetric check, and to literature results. The calculated photon energy spectra at other operating potentials (30 and 40 kV) of the device were also compared to literature data. The calculated energy spectra at all operating voltages are consistent with literature reports. The optimized sub-source has a relative intensity of 5% and an emission direction that is favoured along the axis of the source. The calculated depth dose curve for the bare probe agreed with the reference data, and the isodose lines are similar to published experimental results. Validation of the source model under a more complex experimental setup by film dosimetry agreed to within 2%/1 mm (98% pixel pass rate) of the values calculated with the VSM. We derived a VSM of the 50 kVp INTRABEAM source from a PSF. The dose predicted by the model agreed with reports in literature, reference data from the device manufacturer, and with an independent validation check. The algorithm could be used for treatment planning.

Morphology and ultrastructure of epilithic versus cryptic, microbial growth in lower Cambrian phosphorites from the Montagne Noire, France.

The lower Cambrian grainy phosphorites of the northern Montagne Noire occur interbedded with grey to black, laminated to massive shales and limestones deposited along the edge of a continental shelf, associated with slope-related facies and unstable substrates. The concentration of phosphate took place by repeated alternations of low sedimentation rates and condensation (hardgrounds), in situ early-diagenetic precipitation of fluorapatite, winnowing and polyphase reworking of previously phosphatized skeletons and hardground-derived clasts. The succession of repeated cycles of sedimentation, phosphate concentration, and reworking led to multi-event phosphate deposits rich in allochthonous particles. Phosphogenesis was primarily mediated by microbial activity, which is evidenced by the abundance of phosphatized putative microbial remains. These occur as smooth and segmented filaments, sheaths, and ovoid-shaped coccoids. These simple morphologies commonly form composite frameworks as a result of their aggregation and entanglement, leading to the record of biofilms, microbial mats, and complex networks. These infested the calcitic skeletonized microfossils that littered the substrate. Microbial activity evidences epilithic (anisotropic coatings on skeletons), euendolithic (perforating skeletal walls), and cryptoendolithic (lining inter- and intraparticulate pores) strategies, the latter dominated by bundles of filaments and globular clusters that grew along the cavities of helcionellids and hyoliths. According to their epilithic versus cryptic strategies, microbial populations that penetrated and dwelled inside hard skeletal substrates show different network and colonial morphologies. These early Cambrian shell concentrations were the loci of a stepwise colonization made by saprophytic to mutualistic, cyanobacterial-fungal consortia. Their euendolithic and cryptoendolithic ecological niches provided microbial refugia to manage the grazing impact mainly led by metazoans.

Pharmacodynamic analysis and clinical trial of amoxicillin sprinkle administered once daily for 7 days compared to penicillin V potassium administered four times daily for 10 days in the treatment of tonsillopharyngitis due to Streptococcus pyogenes in children.

An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (T >MIC; based on the MIC(90) of 0.06 microg/ml for Streptococcus pyogenes reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formulation of amoxicillin (amoxicillin sprinkle). The daily T >MIC achieved with the QD amoxicillin sprinkle formulation was comparable to that achieved with a four-times-daily (QID) penicillin VK suspension. An investigator-blinded, randomized, parallel-group, multicenter study involving 579 children 6 months to 12 years old with acute streptococcal tonsillopharyngitis was then undertaken. Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7 days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle and 68.0% (132/194) for penicillin VK (95% confidence interval, -12.0% to 6.6%). Thus, neither antibiotic regimen met the minimum criterion of > or =85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to S. pyogenes. The results of subgroup analyses across demographic characteristics and current infection characteristics and by age/weight categories were consistent with the primary-efficacy result. The clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1% (216/251) and 91.9% (204/222), respectively (95% confidence interval, -11.6% to -0.4%). The results of a post hoc PD analysis suggested that a requirement for 60% daily T >MIC(90) more accurately predicted the observed high failure rates for bacteriologic eradication with the amoxicillin sprinkle and penicillin VK suspension studied. Based on the association between longer treatment courses and maximal bacterial eradication rates reported in the literature, an alternative composite PK/PD target taking into consideration the duration of therapy, or total T >MIC, was considered and provides an alternative explanation for the observed failure rate of amoxicillin sprinkle.

Infrared thermography and ultrasonography to indirectly monitor the influence of liner type and overmilking on teat tissue recovery.

Eight Danish Holstein cows were milked with a 1-mm thick specially designed soft liner on their right rear teat and a standard liner mounted under extra high tension on their left rear teat. Four of the animals were overmilked for 5 min. Rear teats were subjected to ultrasound examination on the first day and to infrared thermography on the second day. Teats were submersed in ethanol 20 min post-milking on the second day. Ultrasonography measurements showed that teat canal length increased by 30-41% during milking. Twenty minutes after milking, teats milked with modified standard liners still had elongated teat canals while teats milked with the soft liner were normalized. Overmilking tended to increase teat wall thickness. Approximately 80% of variability in teat canal length, from before teat preparation to after milking, could be explained by changes during teat preparation. Thermography indicated a general drop in teat temperature during teat preparation. Teat temperature increased during milking and continued to increase until the ethanol challenge induced a significant drop. Temperatures approached pre-challenge rather than pre-milking temperatures within 10 minutes after challenge. Teat temperatures were dependent on type of liner. Mid-teat temperatures post-challenge relative to pre-teat preparation were dependent on overmilking. Thermography and ultrasound were considered useful methods to indirectly and non invasively evaluate teat tissue integrity.

Detergents in the indoor environment - what is the evidence for an allergy promoting effect? Known and postulated mechanisms.

IgE-mediated allergic diseases, such as asthma and rhinitis seem to be increasing in industrialised societies. One possible explanation for this could be the increased use of more effective and aggressive detergents. The surfactants from these could interfere with the sensitisation process in which specific IgE is formed to ubiquitously occurring environmental allergens. Only sparse data exist in relation to surfactants and allergic sensitization. However, it can be speculated that the strong surfactant properties of some of ingredients used in modem detergents may interfere with some of the intricate cellular interactions taking place along the immunological pathways. These include formation of IL-4 and IL-5 producing T helper lymphocytes type 2 and the B-lymphocyte isotype switch, which leads to production of specific IgE. Candidates for experimental studies of such phenomena on the cellular level are proposed.

Study of adjuvant effect of model surfactants from the groups of alkyl sulfates, alkylbenzene sulfonates, alcohol ethoxylates and soaps.

The sodium salts of representatives of anionic surfactants, dodecylbenzene sulfonate (SDBS), dodecyl sulfate (SDS) and coconut oil fatty acids, and a nonionic surfactant, dodecyl alcohol ethoxylate, were studied for adjuvant effect on the production of specific IgE antibodies in mice. The surfactants were injected subcutaneously (sc) in concentrations of 1000, 100, 10 or 1 mg/l, respectively, together with 1 microg of ovalbumin (OVA). In addition, groups of mice received OVA in saline (control group) or in Al(OH)(3) (positive adjuvant control group). After the primary immunization the mice were boosted up to three times with OVA (0.1 microg sc) in saline. OVA-specific IgE antibodies were determined by the heterologous mouse rat passive cutaneous anaphylaxis test. The results were confirmed by a specific ELISA method. After the first booster, the Al(OH)(3) group and the 10 mg/l SDS group showed a statistically significant increase in OVA specific IgE levels. After two boosters, a statistically significant suppression in OVA-specific IgE production occurred with SDS (1000 mg/l), SDBS (1000 and 100 mg/l), coconut soap (1000 mg/l) and the alcohol ethoxylate (10 mg/l). This study suggests that a limited number of surfactants possess an adjuvant effect whereas all surfactants at certain levels can suppress specific IgE production.

Concurrent partial body radiation prevents cytokine mobilization of blood progenitor cells: an effect mediated by a circulating factor.

Mobilization of stem and progenitor cells into blood, which facilitates the collection of blood-derived autograft and allograft products, can be accomplished with administration of myelosuppressive chemotherapy, hematopoietic growth factors, or both. Autologous donor indifference to mobilization attempts has been correlated with prior administration of chemotherapy and radiation therapy. To investigate whether concurrent administration of radiation therapy inhibits mobilization, five daily injections of a potent combination of mobilizing cytokines, 500 U/kg erythropoietin (EPO) plus 15 microg/kg G-CSF, were administered each morning to Balb/c mice. Each afternoon, a 2 Gy fraction of Co-60 radiation was administered to either the lower limb or the upper or lower hemibody. Each day, mice were necropsied, and blood stem cell mobilization was determined by assaying the number of hematopoietic colony-forming cells in the blood and in the spleen. Unirradiated cytokine-injected mice showed a significant mobilization effect evident as increased colony-forming cells in blood and spleen compared with saline-injected unirradiated controls. The irradiated mice showed markedly inhibited or absent mobilization regardless of the part of the body irradiated. To investigate the mechanism of radiation-induced mobilization inhibition, heparinized plasma was obtained from mice whose lower bodies were irradiated with 2 Gy 18 h previously, and 0.5 ml was injected i.v. into intact mice 10 min before they received 15 microg/kg G-CSF and 500 U/kg EPO. Unlike mice that received G-CSF + EPO only and showed mobilization of progenitors from marrow to spleen, recipients of plasma from irradiated mice before and after cytokine administration showed significantly reduced mobilization of progenitors. Thus, radiation-induced inhibition of stem cell mobilization is mediated by an unidentified circulating factor.

On the safety of 5-[125I]iodo-2'-deoxyuridine--Preclinical evaluation in swine.

To increase tumor incorporation and minimize hepatic degradation of radio-IUdR, compartmental administration routes are being considered as an alternative to intravenous (i.v.) injections. Although there are significant data on the biodistribution and some reports on radiotoxicity of i.v.-administered 125IUdR, similar results for other routes of delivery are not available. We have undertaken a series of experiments intended to examine radiation effects of 125IUdR after intravesical (3 swine; eight 3 mCi doses at 4-day intervals), intracarotid (3 swine; two 10 mCi doses at 2-week intervals), and intra-aortic (5 swine, single dose of 10 mCi) administration in a swine model. Liver, renal functions, and complete blood counts were monitored throughout the duration of the experiment. Pharmacokinetics, systemic distribution of radioactivity and metabolites were measured. The normal tissue 125IUdR uptake and histology were determined after necropsy. No adverse systemic effects were identified. Clinical observations, laboratory data, and necropsy results were within normal range.

Measurement of surface temperature and emissivity by a multitemperature method for Fourier-transform infrared spectrometers.

Surface temperatures are estimated with high precision based on a multitemperature method for Fourier-transform spectrometers. The method is based on Planck's radiation law and a nonlinear least-squares fitting algorithm applied to two or more spectra at different sample temperatures and a single measurement at a known sample temperature, for example, at ambient temperature. The temperature of the sample surface can be measured rather easily at ambient temperature. The spectrum at ambient temperature is used to eliminate background effects from spectra as measured at other surface temperatures. The temperatures of the sample are found in a single calculation from the measured spectra independently of the response function of the instrument and the emissivity of the sample. The spectral emissivity of a sample can be measured if the instrument is calibrated against a blackbody source. Temperatures of blackbody sources are estimated with an uncertainty of 0.2-2 K. The method is demonstrated for measuring the spectral emissivity of a brass specimen and an oxidized nickel specimen.

Pharmacoeconomic aspects in the treatment of curable and incurable cancer.

Assessments of the direct and indirect costs of cancer treatment have demonstrated the extreme complexity of these costs. Expenditure on cancer treatment is high, often reaching 3 to 6% of the gross national product in industrialised countries. In this article, we propose that the health outcomes associated with this high expenditure should be analysed in relation to concepts such as total cytoreduction (leading to disease-free survival and cure) and cytostabilisation with acceptable quality of life (in incurable cancer patients). Outcomes appear to be more variable among incurable compared with curable patients, so that cure and survival (which apply to only about 50% of all patients) are not the sole outcome parameters. For the 50% of patients in industrialised countries in whom cure is not possible, outcomes (in the form of cytostabilisation and an ongoing obligation to seek curative cytoreduction) will require further pharmacoeconomic assessment.

Oblique laser-sheet visualization.

A laser-sheet visualization technique is demonstrated in which the laser and camera systems are integrated into a single unit, reducing the need for optical access to a single optical port. The technique is based on the photographing of a plane oblique to the camera optical axis and has been successfully applied to the quarl region of a power-station pulverized coal burner. The geometry of oblique photographing is presented.

[Alcohol related mortality 1980-90, how many children are affected?]. / Alkoholrelaterte dødsfall 1980-90, hvor mange barn er berørt?

During the decade 1980 to 1990, 3,500 persons in Norway, under 30 years of age lost their mother or father as a result of an alcohol-related disease. Many of these persons were small children. The article presents research based on linkage of data from the population census of 1980, causes of death and the population register. The results show large regional differences in the rates of children who lost a parent due to misuse of alcohol. Even larger differences were observed between the different districts within the city of Oslo. Differences in registered sales and the consumption of illicitly distilled alcohol both help to explain the regional differences between counties.

Freud, Piaget, or neither? Beliefs in controlling others by wishful thinking and magical behavior in young children.

Tests showed that 4- to 6-year-old children believe that people can be influenced or "controlled" both by thinking (e.g., both wishful thinking and magical behavior) and by realistic means (e.g., positive reinforcement, example, and group pressure). Belief in control by thinking did not vary by the subjects' sex or age, influence type (wishing or magical behavior), or target response (behavior, emotion, or thought). Quantitative measures, however, suggested that magical behavior was seen by subjects as being more efficient than wishing, and that emotion was considered easier to influence than thinking. Beliefs in control by thinking were not related to a measure of fantasy-reality differentiation (realism).

Seasonal changes in the concentration of the major storage protein and its mRNA in xylem ray cells of poplar trees.

In the autumn large amounts of a major storage protein accumulate in the woody stem of poplar trees. This protein is stored in xylem ray cells during the winter season and is degraded in late spring. The accumulation of this protein is preceded by a dramatic but transient appearance of the corresponding mRNA. Thus, the seasonal change in the mRNA content appears to be a crucial event for the storage of nitrogen in the stem. The amino acid sequence of the storage protein has been deduced from the nucleotide sequence of a full-length cDNA. The cDNA shows a nucleotide sequence similarity of approximately 75% with two published cDNA sequences of poplar which represent transcripts that accumulate systemically in leaves of poplar trees in response to wounding.