Guidelines on the Use of Systemic Therapy in Patients with Advanced Thyroid Cancer.

With increasing understanding of the molecular alterations leading to thyroid cancers in recent years we have seen a rapid increase in the number of effective targeted systemic therapies available for patients with advanced thyroid cancer; firstly with the advent of the multi-kinase inhibitors and more recently with more specific RET, BRAF, MEK, ALK and NTRK inhibitors. Although these developments are very welcome, they have resulted in a paradigm shift in the management of advanced thyroid cancer to which thyroid oncologists have had to rapidly adapt, learning how to supervise treatment safely with novel agents, the management of novel toxicities, when and how to arrange molecular genetic testing of cancers and, perhaps most importantly, determining when the optimum time is to start these treatments in what can often be a relatively indolent, if progressive, disease. We hope that these guidelines will support clinicians in making these decisions with their patients, as well as signposting and providing useful supporting information both for patients and clinicians.

Review: Behavioral signs of estrus and the potential of fully automated systems for detection of estrus in dairy cattle.

Efficient detection of estrus is a permanent challenge for successful reproductive performance in dairy cattle. In this context, comprehensive knowledge of estrus-related behaviors is fundamental to achieve optimal estrus detection rates. This review was designed to identify the characteristics of behavioral estrus as a necessary basis for developing strategies and technologies to improve the reproductive management on dairy farms. The focus is on secondary symptoms of estrus (mounting, activity, aggressive and agonistic behaviors) which seem more indicative than standing behavior. The consequences of management, housing conditions and cow- and environmental-related factors impacting expression and detection of estrus as well as their relative importance are described in order to increase efficiency and accuracy of estrus detection. As traditional estrus detection via visual observation is time-consuming and ineffective, there has been a considerable advancement of detection aids during the last 10 years. By now, a number of fully automated technologies including pressure sensing systems, activity meters, video cameras, recordings of vocalization as well as measurements of body temperature and milk progesterone concentration are available. These systems differ in many aspects regarding sustainability and efficiency as keys to their adoption for farm use. As being most practical for estrus detection a high priority - according to the current research - is given to the detection based on sensor-supported activity monitoring, especially accelerometer systems. Due to differences in individual intensity and duration of estrus multivariate analysis can support herd managers in determining the onset of estrus. Actually, there is increasing interest in investigating the potential of combining data of activity monitoring and information of several other methods, which may lead to the best results concerning sensitivity and specificity of detection. Future improvements will likely require more multivariate detection by data and systems already existing on farms.

Influence of estrus on dry matter intake, water intake and BW of dairy cows.

The objectives of this study were to analyze whether dry matter intake (DMI), water intake (WI) and BW were influenced by estrus. A second objective was to determine whether correlations exist among these traits in non-estrous days. Data collection included 34 Holstein-Friesian cows from the research farm 'Haus Riswick' of the Agricultural Chamber North Rhine-Westphalia, Germany. On an individual basis, daily DMI and daily WI were measured automatically by a scale in the feeding trough and a WI monitoring system, respectively. BW was determined by a walk-through scale fitted with two gates - one in front and one behind the scale floor. Data were analyzed around cow's estrus with day 0 (the day of artificial insemination leading to conception). Means during the reference period, defined as days -3 to -1 and 1 to 3, were compared with the means during estrus (day 0). DMI, WI and BW were affected by estrus. Of all cows, 85.3% and 66.7% had reduced DMI and WI, respectively, on day 0 compared with the reference period. Lower BW was detected in 69.2% of all cows relative to the reference period. During the reference period, average DMI, WI and BW were 23.0, 86.6 and 654.8 kg. A minimum DMI of 20.4 kg and a minimum BW of 644.2 kg were detected on the day of estrus, whereas the minimum WI occurred on the day before estrus. After estrus, DMI, WI and BW returned to baseline values. Intake of concentrated feed did not seem to be influenced by estrus. Positive correlations existed between daily DMI and daily WI (r=0.63) as well as between cows' daily BW and daily WI (r=0.23). The results warrant further investigations to determine whether monitoring of DMI, WI and BW may assist in predicting estrus.

Effect of phenylephrine on the haemodynamic state and cerebral oxygen saturation during anaesthesia in the upright position.

BACKGROUND: The upright sitting or beachchair position is associated with hypotension, risk of cerebral hypoperfusion, and cerebral injury. We hypothesized that by increasing arterial pressure with phenylephrine administration, cerebral perfusion, and postoperative recovery would be improved. METHODS: Thirty-four patients undergoing elective shoulder surgery were randomized to receive either saline or phenylephrine infusion (PE) 5 min before being placed in the upright position. Simultaneous measurements of mean arterial pressure, cerebral oxygen saturation, middle cerebral artery velocity, and cardiac function using transthoracic echocardiography were made. Postoperative neurocognitive function was assessed. RESULTS: At the commencement of PE, mean (SD) cerebral oxygen saturation significantly decreased from 77 (10) to 67 (13)% (P=0.02), and further to 59 (11) % on upright positioning. The level of cerebral saturation upright was not significantly different to patients receiving saline (P=0.07), with values remaining at room-air levels. Middle cerebral artery blood velocity increased by 20% (P=0.04). Phenylephrine prevented hypotension in the upright position primarily by maintaining preload and increasing systemic vascular resistance (P=0.01), and was associated with a decrease in cardiac output. No postoperative neurocognitive dysfunction was identified. CONCLUSIONS: Despite maintaining arterial pressure with phenylephrine, cerebral desaturation occurred with upright positioning. Cerebral oxygen saturation can provide a valuable endpoint when evaluating the effect of vasopressor therapy on cerebral perfusion.

Relationship between daily rumination time and estrus of dairy cows.

The aim of the study was to investigate whether rumination time (RT) was related to estrus in dairy cattle. On 4 farms, cows were equipped with a microphone-based sensor system that allowed continuous recording (in blocks of 2 h) of RT. The analyzed data set consisted of 265 verified estrus cycles of 224 animals with artificial insemination leading to conception. The day of estrus (d 0) was defined as the day when estrus was identified either by measurement of physical activity or by visual observation. In estrous cows, RT was significantly reduced. With a duration of 355 min/d, the minimum RT was found on the day of estrus compared with the base level of 429 min/d during the reference period (the mean of 3 d before and 3 d after estrus). The average decrease in RT was 17% (74 min), ranging between -71 and +16% among animals. Herd and parity affected the RT decrease during estrus. Among the 4 analyzed herds, the RT decrease of cows in estrus ranged between 14% (60 min/d) and 24% (94 min/d). The decrease in RT was more pronounced in primiparous than in mature cows. In conclusion, RT is reduced on the day of estrus on average. The RT decrease during estrus was characterized by high variation among cows.

Relationship between accommodative and vergence dysfunctions and academic achievement for primary school children.

The purpose of this study was to investigate the prevalence and types of non-strabismic accommodative and/or vergence dysfunctions in primary school children, and to determine the relationship of these dysfunctions to academic achievement. A total of 1031 parents and their children aged 9-13 years responded to the College of Optometrists in Vision Development Quality of Life (COVD-QOL) questionnaire. Of these, 258 children whose visual symptom scores were > or =20 were identified for further evaluation. Comprehensive eye and vision examinations were provided to the children who met the eligibility criteria (114 of 258): eligible symptomatic children were those without amblyopia, strabismus, ocular and systemic pathology, and contact lens wear. Children were also excluded if they had visual acuity poorer than 20/25 in either eye or vertical phoria >1 prism diopter. The results showed that 82 of 114 (71.9%) of criteria-eligible symptomatic primary school children had non-strabismic accommodative and/or vergence dysfunctions. In addition, a significant relationship was found between these dysfunctions and academic scores in every academic area (reading, mathematics, social science and science) in the total sample. Therefore, accommodative and vergence functions should be tested for all school children who have visual symptoms and/or academic difficulties. Additional study is needed to determine if improvements of accommodative and vergence functions also improve academic achievement.

Continuous monitoring of ear temperature in boars.

Seventy boars penned singly in an artificial insemination station were included in this analysis. Each had a special ear tag with an integrated sensor to measure the skin temperature of the ear every 3 min. The readings were averaged per animal and hour, thus, over 18 months, resulted in a total of 37,7351 data points. In the whole investigation period, the system did not work for some days and some sensors did not work for hours. A diurnal rhythm was found for the ear temperature with its minimum reached between 5 and 6 am (22.07 degrees C) and the maximum between 4 and 6 pm (28.90 degrees C). If the ambient temperature was increased by 5 Kelvin then the skin temperature at the ear also increased by 3 to 5 Kelvin. On days when semen was collected, the ear temperature was higher during the relevant hours than at comparable times on days without semen collection. The results of 322 measurements taken from 70 boars, including 24 boars with increased rectal temperature (> 39.3 degrees C), showed that the coefficient of correlation between skin and rectal temperature was low (r = 0.36). Thus, the measurement of the skin temperature at the ear cannot be used as a significant or safe parameter for predicting the rectal temperature and sowith the health status of the animal.

Comparison between the physiological response to roller skiing and in-line skating in biathletes.

PURPOSE: Roller skiing is frequently used in Nordic disciplines during the off-season periods. Recently, in-line skating has become a potential alternative. In the present study, the responses of heart rate, oxygen uptake, respiratory exchange ratio, and lactic acid concentration to roller skiing and in-line skating were compared in competitive biathletes. METHODS: Eight male subjects performed three tests with both devices on a hilly outdoor track. They were requested to adjust their speed in such a way that the following criteria were met: intensity 1, lactate concentration about 2 mmol x L(-1); intensity 2, lactate concentration about 4 mmol x L(-1); AND intensity 3, maximal speed. RESULTS: Though the subjects were not experienced in-line skaters, all managed to adjust the required intensities. This was achieved through increased velocities during in-line skating. Independent of the exercise intensity the differences in speed ranged between 1.0 and 1.4 m x s(-1). The relationships between lactic acid concentration, oxygen uptake, respiratory exchange ratio, and heart rate were not influenced by the test device. The respiratory exchange ratio amounted to 0.88, 0.95, and 1.02 for intensities 1 to 3, respectively. CONCLUSIONS: These results show that in-line skating can be regarded as an alternative to roller skiing for off-seasonal training in Nordic disciplines. A potential advantage of in-line skating is that aerobic training intensities can be obtained at competitive velocities.

[Effect of various factors on the suckling behavior of domestic rabbits]. / Untersuchungen zum Einfluss verschiedener Faktoren auf das Säugeverhalten bei Hauskaninchen.

An average number of 1.47 suckling events per 24 hours with a mean duration of 203 seconds per suckling was shown in investigations with 156 does (253 litter, 1.907 alive born pups) by continuous video recordings (infrared technique) over 1.045 periods with 24 hours. Two or more suckling periods with maximum of six sucklings per 24 h were recorded in 40% of all days. Number and duration of suckling events and also percentage of days with > or = 2 sucklings/24 hours were significantly influenced by genotype of does, parity and keeping system (flatdeck, get-away-cage). ZIKA-hybrids had the highest percentage of days with several suckling periods (52.7). Suckling activity had shown a circadian rhythm and was significantly correlated with dawn (light-dark as an inducing factor for suckling). 25% of all suckling events took place in the hour after the lights were turned off.

[Nursing and suckling behavior and mother-child contacts in domestic rabbits]. / Untersuchungen zum Säuge- und Saugverhalten und zur Mutter-Kind-Beziehung bei Hauskaninchen.

Investigations with 34 litters of rabbits breed White New Zealands by the help of infrared videotechnique over 242 day-night-periods (24 hr per period) showed a frequency of 15.1 mother-child-contacts on average of 24 hr (Min: 6, Max: 48 contacts a day). In 38% of all 24-hr-cycles observed one suckling event was found and in 56.6% of all cases two up to five suckling periods were seen (5.4% of all 24-hr-periods were without suckling). Mean suckling frequency per 24 hr was 1.83 with maximum in second suckling week (2.31). Highly significant positive coefficients of correlation (r = 0.33 up to r = 0.89) were found between birth weight, daily gain, milk intake and weaning weight. Mother-child-relations in rabbits (breed White New Zealands) are more intensive as thought up to now so that the separation of mother from her litter represents an intervention into species-specific behaviour.

[Investigations on the concentration and emission of ammonia and nitrous oxide in various deep litter keeping systems for fattening pigs and in slatted floor keeping]. / Untersuchungen zu Konzentration und Emission von Ammoniak und Lachgas bei verschiedenen Tiefstreuhaltungssystemen für Mastschweine und bei Vollspaltenbodenhaltung.

Concentration of ammonia and nitrous oxide was measured in an air conditioned pig site with two chambers during six rounds (app. 650 measuring days) with different deep litter and a slatted floor keeping system for fattening pigs. Emissions and gaseous nitrogen losses were calculated. With exception of a system with mixing twice a week deep litter keeping leads to decrease of NH3 concentration (up to 26%), partly also of NH3 emission, but to higher N2O emissions compared to liquid manure system. With exception of ENVIROZYME deep litter keeping all other deep litter systems cause higher gaseous nitrogen losses compared to slatted floor keeping.

[Results of behavioral investigations of broilers kept on various litter materials]. / Ergebnisse von Verhaltensuntersuchungen bei Masthähnchen auf verschiedenen Einstreumaterialien.

Behavioural investigations by the help of time-sampling-method with broilers kept on different litter materials (wood chip deep litter with or without mixing, straw resp.) in 5 rounds (per round investigated: 5 days x 8 hours x 12 values/hr x 10 broilers = 24000 behavioural data) showed no evident differences between keeping systems which could lead to preferring or rejecting a system. A lower frequency of scratching and ground pecking and a higher percentage of comfort behaviour was found in broilers kept on straw because of increasing amount of faeces and compression of litter material. From the view point of ethology and animal hygiene wood chip deep litter system without mixing and a 10 cm layer of new wood pieces after every round could be recommended if economical aspects allow.

[Dust concentration in deep litter with special reference to activity of growing pits and to the use aerosol application]. / Untersuchungen der Schwebstaubkonzentration bei Tiefstreuhaltung unter Berücksichtigung der Aktivität von Mastschweinen und bei Anwendung einer Aerosolapplikation.

Results of continuous measurements of dust during 24 hours on 22 days in one round and of behavioural investigations at the same time have shown a high correlation of both parameters (dust concentration; locomotoric activity of fattening pigs) over a 24 hour-cycle with biphasic dynamics (two phases with increased values: after morning feeding between 7 and 9 a.m. and in the afternoon between 1 and 3 p.m.). The hour-averages of both variables (n = 528) demonstrated a highly significant positive correlation (r = 0.73; p < 0.01); dust concentration is increasing with increasing animal activity. It is necessary to consider the dynamics of dust values over 24 hours in measuring and evaluating concentration or emission of dust under the aspects of animal and environmental hygiene. A reduction of dust concentration up to 18% is possible by using an aerosol-application of soybean oil-emulgator over 24 hours with an amount of 80-85 ml per square meter and 24 hr.

[Results of continuous gas measurements rabbit housing by using multi-gas monitoring]. / Ergebnisse kontinuierlicher Gasmessungen in der Mastkaninchenhaltung mit Hilfe des Multigasmonitoring.

Investigations of slatted floor keeping of rabbits in an air conditioned chamber with multigas monitoring over a period of more than two month have shown that the average values per week were on a low level between 575 and 685 ppm (carbon dioxide), 3.4 and 5.6 ppm (ammonia) resp. Concentration of ammonia reached in maximum 12.3 ppm for a short time. Nitrous oxide concentration was measured on a global value (253 up to 317 ppb). A slight tendency of increasing CO2 and NH3 values with the begin of light period--obviously related to increased locomotoric activity--approximately was observed. In slatted floor keeping calculated emission of ammonia was very low (0.23 gram per 500 kg an hour).

[Dust emission from chicken and layer houses]. / Untersuchungen zur Staubemission aus Geflügelintensivhaltungen.

Dust concentration was measured by Laser-monitor in two at a time houses for layers with litter or with cages and in two at a time houses for growing chicken with litter or with cages in the middle of the keeping area, in the outlet opening and in 3, 10, 50 and 100 m distance over a period of 8 weeks in winter, summer and spring/autumn. Dust values have shown only less dynamics between 8 am and 5 pm. Significant positive correlation was found between dust concentration and age of poultry, keeping time resp. in litter housing system but not in cage housing system. Also, it was demonstrated a significant relation between dust concentration inside of poultry house, at the outlet openings and in 3 m distance in the outdoor air. There was no influence evident of indoor dust concentration on the dust value in the environment in more than 3 m distance to the poultry house. It was shown a low dust concentration of 0.1% up to 2.1%--compared to the indoor dust values--in 50 and 100 m distance to outlet ventilation system independent on housing, climatic and topographic factors.

[Determination of concentration and emission of gases relevant to animal and environmental hygiene in different systems for fattening of pigs with the aid of multigas monitoring]. / Zur Bestimmung von Konzentration und Emission tier- und umwelthygienisch relevanter Gase bei verschiedenen Schweinehaltungssystemen mit Hilfe des Multigas-monitoring.

Multigasmonitoring is a method to measure continuously gases relevant from the view point of animal and environmental hygiene with high sampling rate and to calculate emission. The methodical procedure has been described by example from different deep litter systems with additives and slatted floor system with liquid manure storage for fattening pigs. It has been shown that the emission of ammonia from an obviously good working deep litter system can be lowered by approximately 30% in comparison with slatted floor. The mean concentration of nitrous oxide in deep litter system with additives was approximately 2 ppm, whereas in the liquid manure system the N2O concentration was less than the outdoor value.

ED points and NOELs: how they are used by UK pesticide regulators.

: The availability and use of ED point and NOEL values in ecotoxicological data submitted to the UK Pesticides Safety Directorate is explored. In first tier data normally submitted for pesticide registration, ED points such as EC/LC/LD50s are commonly available from acute laboratory toxicity studies conducted using birds, small mammals, fish, aquatic invertebrates, plants, honeybees and earthworms. These ED points are subsequently used for hazard classification of the pesticide and in toxicity: exposure ratio (TER) calculations required during the acute risk assessment. Although NOELs can often be available from the same first tier data, they are generally not used. However, NOELs commonly available from higher tier chronic toxicity studies such as chronic fish, Daphnia reproduction and avian reproduction studies, are used in TER calculations to assess chronic risk. The statistical limitations of the NOEL are recognized and the regulatory implications of replacing the NOEL with an alternative ED point are discussed.

[Results of multi-gas analysis in the raising of fattening swine in composted stalls or on slatted floors]. / Ergebnisse der Mehr-Gas-Analyse bei der Haltung von Mastschweinen im Kompoststall bzw. auf Spaltenboden.

Using continuous multigasmonitoring on the basis of photoacoustic spectralanalysis a mean concentration of ammonia of 8.1 ppm, nitrous oxide of 2.1 ppm and carbon dioxide of 0.12 Vol.-% was measured in a deep litter system for fattening pigs with additives. In slatted floor system with liquid manure storage the average concentration of ammonia (11.9 ppm) was significantly higher at the same period, whereas the concentration of nitrous oxide was appr. 0.2 ppm. Concentration of carbon dioxide in liquid manure system was lower (0.10 Vol.-%) than in deep litter system.

[Effect of housing of sows during parturition and the vitality of the piglets]. / Einfluss der Haltung der Sauen auf den Geburtsverlauf und die Vitalität der Ferkel.

Group housing of sows had a positive effect on parturition, but led to a decrease in litter size by 1.2 alive born piglets per litter and a reduce in mean birth weight of piglets by 70 g; it had no effect on the vitality of piglets. A high birth weight, a long lasting placento-fetal blood transfer and an air temperature of more than 20 degrees C are factors with significant influence on vitality of neonates.