Dose constraints for whole breast radiation therapy based on the quality assessment of treatment plans in the randomised Danish breast cancer group (DBCG) HYPO trial.

PURPOSE: Quality assessment of the treatment plans in the Danish Breast Cancer Group (DBCG) HYPO trial was carried out based on prospectively reported dosimetric parameters and evidence-based dose constraints for whole breast radiation therapy were derived. MATERIALS AND METHODS: From 2009 to 2014, 1882 patients (pts) were randomised between 50 Gy/25fractions (fr) versus 40 Gy/15fr. Doses to CTVp_breast (V95%, V107%-V110%, Dmax, and in addition for 40 Gy plans V105%-V107%), ipsilateral lung (V20Gy/V17Gy), heart (V20Gy/V17Gy, V40Gy/V35Gy), and left anterior descending coronary artery (LADCA) (Dmax) and use of respiratory gated technique were prospectively reported to the DBCG database. After end of accrual, these dosimetric parameters from all plans in the trial were compared to the pre-specified treatment constraints. RESULTS: In total, 1854 pts from eight radiation therapy (RT) centres in three countries were treated. No statistically significant differences were found between the results for 40 Gy and 50 Gy plans, except for CTVp_breast hot-spot volume (V107%-V110%). Of the 40 Gy pts, 90% with CTVp_breast > 600 mL and 95% with CTVp_breast ≤ 600 mL had a CTVp_breast hot-spot volume (V105%-V107%) <2%. In 95% of the 50 Gy plans, the CTVp_breast absolute hot-spot volume (V107%-V110%) was <0.5 mL and 1.7 mL for CTVp_breast ≤ 600 mL and > 600 mL, respectively. Compliance was >99% for both heart and lung constraints. Largest deviation from protocol constraints was found for the volume of CTVp_breast covered with 95% of the prescription dose or more (V95%). The CTV dose coverage (V95%) was >94.3% in 95% of the right-sided pts, whereas the figures for 95% of the left-sided pts treated with and without respiratory gating were 93.2% and 88.8%, respectively. CONCLUSION: A high degree of compliance with protocol dose constraints was found for treatment plans in the DBCG HYPO trial. New constraints for dose to organs at risk and high-dose volumes in the breast are suggested for breast-only RT planning.

Animal responses to herbage allowance: Forage intake and body weight gain of sheep grazing the Inner Mongolian steppe - Results of a six-year study.

An increasing human population and the growing demand for food of animal origin are leading to an intensification of sheep production and widespread overgrazing of the grassland steppe in Inner Mongolia. The aim of this study was to analyze the effect of herbage allowance (HA) on OM intake (OMI) and BW gain (BWG) of grazing sheep. In July to September 2005 to 2010, a grazing experiment was conducted in the Xilin River Basin using 15-mo-old female Mongolian fat-tailed sheep (31.5 kg BW [SE 0.2]). Six HA classes were tested on 4 experimental plots per HA class that were alternately used for grazing and haymaking each year (i.e., = 2 grazed plots per HA class and year). Mean HA ranged from 15.4 (SD 4.0) to 1.5 kg (SD 0.8) herbage DM/kg BW in HA class 1 to 6, respectively. In 6 sheep per plot (4 sheep in 2009 and 2010), OMI and BWG were determined. Titanium dioxide was used to determine fecal excretion, and digestibility of ingested OM was estimated from CP concentration in feces. Fecal grab samples were collected during 5 d each in July, August, and September. The animals were weighed monthly. Daily OMI of sheep ranged between 68 and 89 g/kg BW and was not affected by HA class ( = 0.373), so that total OMI per hectare was exponentially decreased with increasing HA (root mean square error [RMSE] ≤ 0.31 g/d; ≤ 0.003 for the slope estimates). The BWG of individual sheep increased with increasing HA in 2 of the 6 yr (RMSE 18.4 g/d; ≤ 0.175 for the positive slope estimates). Nevertheless, BWG per hectare strongly decreased with increasing HA (RMSE 0.25 g/d; ≤ 0.006 for the slope estimates). These data support the common practice of farmers to manage the grassland at low HA to allow for greater animal performance per unit of land area.

Insight into the beneficial immunomodulatory mechanism of the sevoflurane metabolite hexafluoro-2-propanol in a rat model of endotoxaemia.

Volatile anaesthetics such as sevoflurane attenuate inflammatory processes, thereby impacting patient outcome significantly. Their inhalative administration is, however, strictly limited to controlled environments such as operating theatres, and thus an intravenously injectable immunomodulatory drug would offer distinct advantages. As protective effects of volatile anaesthetics have been associated with the presence of trifluorinated carbon groups in their basic structure, in this study we investigated the water-soluble sevoflurane metabolite hexafluoro-2-propanol (HFIP) as a potential immunomodulatory drug in a rat model of endotoxic shock. Male Wistar rats were subjected to intravenous lipopolysaccharide (LPS) and thereafter were treated with HFIP. Plasma and tissue inflammatory mediators, neutrophil invasion, tissue damage and haemodynamic stability were the dedicated end-points. In an endotoxin-induced endothelial cell injury model, underlying mechanisms were elucidated using gene expression and gene reporter analyses. HFIP reduced the systemic inflammatory response significantly and decreased endotoxin-induced tissue damage. Additionally, the LPS-provoked drop in blood pressure of animals was resolved by HFIP treatment. Pathway analysis revealed that the observed attenuation of the inflammatory process was associated with reduced nuclear factor kappa B (NF-κΒ) activation and suppression of its dependent transcripts. Taken together, intravenous administration of HFIP exerts promising immunomodulatory effects in endotoxaemic rats. The possibility of intravenous administration would overcome limitations of volatile anaesthetics, and thus HFIP might therefore represent an interesting future drug candidate for states of severe inflammation.

The effect of knee brace and knee sleeve on the proprioception of the knee in young non-professional healthy sportsmen.

BACKGROUND: Proprioception has been defined as the capacity to feel the position of a joint in space as sensed by the central nervous system. Prophylactic knee braces are supposed to help in knee injury prevention not just with a mechanical support of the joint but also improving proprioception. The main aim of this study was to determine the effects of a knee brace and a knee sleeve on knee proprioception. The secondary aim was to determine if different starting angles of the knee and different movement directions influence knee proprioception. METHODS: We tested a group of twenty healthy male sport students without knee injuries. They were tested with the brace, with the sleeve and without support. The threshold of detection of passive knee movement with a starting knee angle of 30° and 60°, both in flexion and extension was determined. RESULTS: We did not find any statistically significant change in the threshold of detection of passive knee movement wearing the brace or the sleeve compared to the unsupported condition (p=0.462, α=0.05). We found a significantly lower proprioceptive sensitivity starting at the more flexed knee angle (p=0.005, α=0.05) and moving in extension than in the other test situations (p=0.001, α=0.05). CONCLUSION: Movement direction and starting position appear to influence the threshold of detection of passive knee movement. The results of this study also suggest that knee supports do not influence either positively or negatively knee proprioception of uninjured active subjects.

Simultaneous confidence intervals on multivariate non-inferiority.

We discuss the analysis of non-inferiority trials based on a multi-armed design with multiple correlated endpoints. We consider five different scenarios: (1) global non-inferiority; (2) non-inferiority for subsets of comparisons; (3) global non-inferiority for a treatment group; (4) global non-inferiority for an endpoint; and (5) local non-inferiority. We describe and compare related approaches, which are based on the union-intersection and intersection-union test principles - alone and in combination. Because non-inferiority thresholds for many differently scaled endpoints are rarely available in practice, the approaches described focus on the estimation of simultaneous confidence limits and their post hoc interpretation on non-inferiority. We discuss and demonstrate pros and cons by means of a real data example.

In vitro exposure of human fibroblasts to local anaesthetics impairs cell growth.

Lidocaine, bupivacaine or ropivacaine are used routinely to manage perioperative pain. Sparse data exist evaluating the effects of local anaesthetics (LA) on fibroblasts, which are involved actively in wound healing. Therefore, we investigated the effects of the three LA to assess the survival, viability and proliferation rate of fibroblasts. Human fibroblasts were exposed to 0·3 mg/ml and 0·6 mg/ml of each LA for 2 days, followed by incubation with normal medium for another 1, 4 or 7 days (group 1). Alternatively, cells were incubated permanently with LA for 3, 6 or 9 days (group 2). Live cell count was assessed using trypan blue staining. Viability was measured by the tetrazolium bromide assay. Proliferation tests were performed with the help of the colorimetric bromodeoxyuridine assay. Production of reactive oxygen species (ROS) was determined, measuring the oxidation of non-fluorescent-2,7'-dichlorofluorescin. Treatment of cells with the three LA showed a concentration-dependent decrease of live cells, mitochondrial activity and proliferation rate. Group arrangement played a significant role for cell count and proliferation, while exposure time influenced viability. Among the analysed LA, bupivacaine showed the most severe cytotoxic effects. Increased production of ROS correlated with decreased viability of fibroblasts in lidocaine- and bupivacaine-exposed cells, but not upon stimulation with ropivacaine. This study shows a concentration-dependent cytotoxic effect of lidocaine, bupivacaine and ropivacaine on fibroblasts in vitro, with more pronounced effects after continuous incubation. A possible mechanism of cell impairment could be triggered by production of ROS upon stimulation with lidocaine and bupivacaine.

Alpha rhythm and hypofrontality in schizophrenia.

OBJECTIVE: To reveal the EEG correlates of resting hypofrontality in schizophrenia (SZ). METHOD: We analyzed the whole-head EEG topography in 14 patients compared to 14 matched controls by applying a new parameterization of the multichannel EEG. We used a combination of power measures tuned for regional surface mapping with power measures that allow evaluation of global effects. RESULTS: The SZ-related EEG abnormalities include i) a global decrease in absolute EEG power robustly manifested in the alpha and beta frequency bands, and ii) a relative increase in the alpha power over the prefrontal brain regions against its reduction over the posterior regions. In the alpha band both effects are linked to the SZ symptoms measured with Positive and Negative Symptom Scales and to chronicity. CONCLUSION: As alpha activity is related to regional deactivation, our findings support the concept of hypofrontality in SZ and expose the alpha rhythm as a sensitive indicator of it.

[Body condition and frequency of ovarian cysts in Brown Swiss cows during the first 40 days of lactation]. / Körperkondition und Häufigkeit von Ovarialzysten bei Braunviehkühen während der ersten 40 Laktationstage.

For this investigation 50 Brown Swiss cows from 21 different farms were used. Twenty-five peripartal overconditioned cows (back fat thickness > 38 mm) were compared with 25 peripartal not overconditioned animals (back fat thickness < 38 mm). On days 20, 30 and 40 post partum the ovaries were examined sonographically and 10, 15, 20, 30 and 40 days after calving plasma concentrations of progesterone and 17-beta estradiol were determined. In peripartal overconditioned animals 12 ovarian cysts were found while only one cyst was present in not overconditioned cows (P < 0.05). At first examination all ovarian cysts were classified by ultrasound as follicle theca cysts (progesterone < 0.5 ng/ml plasma). Follow examinations resulted in 3 cysts which persisted as theca cysts while 8 cysts became luteinized and 2 cysts completely regressed. There was no indication of increased plasma progesterone and/or estradiol concentrations in overconditioned cows with higher fat deposit before of ovarian cysts had occurred.

Persistent clusters in lattices of coupled nonidentical chaotic systems.

Two-dimensional (2D) lattices of diffusively coupled chaotic oscillators are studied. In previous work, it was shown that various cluster synchronization regimes exist when the oscillators are identical. Here, analytical and numerical studies allow us to conclude that these cluster synchronization regimes persist when the chaotic oscillators have slightly different parameters. In the analytical approach, the stability of almost-perfect synchronization regimes is proved via the Lyapunov function method for a wide class of systems, and the synchronization error is estimated. Examples include a 2D lattice of nonidentical Lorenz systems with scalar diffusive coupling. In the numerical study, it is shown that in lattices of Lorenz and Rossler systems the cluster synchronization regimes are stable and robust against up to 10%-15% parameter mismatch and against small noise.

Hierarchy and stability of partially synchronous oscillations of diffusively coupled dynamical systems

The paper presents a qualitative analysis of an array of diffusively coupled identical continuous time dynamical systems. The effects of full, partial, antiphase, and in-phase-antiphase chaotic synchronizations are investigated via the linear invariant manifolds of the corresponding differential equations. The existence of various invariant manifolds, a self-similar behavior, and a hierarchy and embedding of the manifolds of the coupled system are discovered. Sufficient conditions for the stability of the invariant manifolds are obtained via the method of Lyapunov functions. Conditions under which full global synchronization cannot be achieved even for the largest coupling constant are defined. The general rigorous results are illustrated through examples of coupled Lorenz-like and Rossler systems.

Introducing student nurses to critical care: shadow a critical care nurse.

The lack of student experience in critical care makes it difficult for graduate nurses to anticipate what expectations and demands might confront them in intensive care. Consequently, some new graduates discounted critical care as an opportunity available to them. Our institution believed that critical care had special qualities and if those qualities could be demonstrated to nurses, recruitment would improve. An unexpected benefit from the program was the positive staff nurse response to showcasing their skills and expertise. The success of the program was evidenced by the student evaluations and the hiring of students. To date, seven nursing students out of 20 who attended the program have been hired by the hospital. The long-term impact of the program on retention and recruitment is difficult to predict. The department will track these students, as they do all new hires; however, the initial success warranted continuation of the program. Student response to the program has resulted in plans to expand the "shadow a nurse" concept housewide to showcase the nursing specialities such as rehabilitation, maternal/child health, oncology, orthopedics, chemical dependency, and critical care. Current planning involves designing a program aimed toward high school students, with the goal of encouraging young people to consider nursing as a career.

The effect of oxygen administration on oral temperature assessment.

No research data are available on the effects of oxygen on oral temperature. This study sought to determine if oxygen administration via aerosol mask, venti-mask, or nasal prongs altered oral temperature as assessed in the sublingual pockets of the mouth. The population included 40 healthy male and female volunteers. Oxygen was administered using a repeated measure design with the subjects serving as their own controls and the oxygen devices presented in a counterbalanced order. An electronic thermometer recorded the temperature at the end of each 15-minute treatment/control period. There was no significant difference between the pre- and post-treatment measurements of the aerosol mask, venti-mask, and nasal prongs. The conclusion was that oral temperature assessed in the presence of oxygen administration is no different than oral temperature assessed without oxygen administration.

The persistence and possible externalization of axonal debris during Wallerian degeneration.

The sequence of changes in transected rat sciatic nerves were subjected to parallel ultrastructural and biochemical studies. Widespread granular disintegration of axoplasmic microtubules and neurofilaments occurred in the 24--72 hour interval following nerve transection. These changes were associated with a loss of neurofilament proteins and a marked enhancement of 53,000, 70--73,000 and 85,000 MW proteins in transected nerve. The emergence of prominent nerve proteins during the aftermath of axonal degeneration supports their derivation from axonal sources. These three proteins remained prominent components in transected nerves and comprised the major proteins found in 34-day transected nerves. Amorphous granular breakdown products from myelinated and unmyelinated nerve fibers were encountered with progressively decreasing frequency after 48 hours. This diminution of intracellular axonal debris was accompanied by the appearance and increasing prominence of amorphous granular deposits within the endoneurium of transected nerves. These endoneurial deposits became closely associated with collagen fibers and persisted as a prominent component in 34-, 80- and 120-day transected nerves. It is suggested that the amorphous endoneurial granular deposits arise in part from the externalization of granular axoplasmic breakdown products. Externalized axonal components could have important implications for tissue reaction to injury.

Characterization of the calcium-induced disruption of neurofilaments in rat peripheral nerve.

Transverse frozen sections of desheathed rat peripheral nerve were incubated in media of different composition prior to fixation and processing for electron microscopic examination. Neurofilaments remained intact when these tissues were incubated in calcium-free media. A loss of neurofilaments and their replacement by granular debris occurred in myelinated and unmyelinated fibers following incubation in media containing 2 mM calcium. The calcium-mediated disruption of neurofilaments was inhibited by preincubation or incubation with 1 mM p-chloromercuribenzoate (PCMB). The inhibition by preincubation with PCMB could be partially reversed by subsequent preincubation with 10 mM dithioerythritol (DTE). Calcium-mediated breakdown of neurofilaments did not occur after prolonged preincubation in calcium-free media, a finding which suggested that neurofilament disruption was dependent upon a tissue factor which could be lost or inactivated in frozen-sectioned nerve tissues. The findings of the present study provide morphological evidence that neurofilament disruption in mammalian peripheral nerve is mediated by a calcium-activated, PCMB-sensitive enzyme in the axoplasm of myelinated and unmyelinated nerve fibers.

[Thrombocyte migration test as a sensitive tolerance test before platelet substitution (proceedings)]. / Thrombozyten-Migrations-Test als empfindlicher Verträglichkeitstest vor Plättchensubstitution.

Thrombocytopenic patients refractory to random-donor platelet support can usually be substituted by platelets obtained from donors identical with respect to HLA-A and -B antigens [1]. Since such "full-house" identity is rarely available, reliable cross-match tests (CM) are needed in order to pick out donors compatible in spite of HLA non-identity. By use of the thrombocyte migration test (TMT), DUQUESNOY et al. have shown that antiplatelet antibodies may exert an inhibitory effect on platelet migration. Therefore, we have explored this test system for its efficiency as CM compared with the "long-time" lymphocyte cytotoxicity test (LLT). Of 8 sera from polysensitized patients, serial dilutions were performed and simultaneously tested by TMT and LLT with cells obtained from the same control individuals. The sensitivity of TMT exceeded LLT by 2-4 dilution steps in all sera tested. Moreover, 9 patients with incompatible transfusion responses to single-donor platelets in spite of negative LLT had the following results in TMT with pre-transfusion sera: 5 positive (i.e. migration inhibition), 1 negative: enhanced migration was observed 3 times. This phenomenon of enhancement remains to be clarified, since low titers of anti-HLA-antibodies do not cause enhanced platelet migration. Repeated transfusion of platelets obtained from the same donor may cause antibody production against leukocytic antigen not shared by platelets, leading to "false-positive" LLT. 2 patients were successfully substituted with platelets from HLA/MLC-identical siblings in spite of positive LLT, but with negative TMT; in 2 cases with unrelated HLA-A and -B identical donors, TMT results were inconsistent.