A phase II clinical trial evaluating the safety and efficacy of durvalumab as first line therapy in advanced and metastatic non-small cell lung cancer patients with Eastern Cooperative Oncology Group performance status of 2.

Background: Approximately 30-40% of patients with advanced and metastatic non-small cell lung cancer (NSCLC) present with an impaired performance status (PS). There are limited prospective data on the safety and efficacy of durvalumab in these patients.

Methods: In this single-arm phase II clinical trial (NCT02879617), patients with previously untreated Stage IIIB/IV NSCLC and ECOG PS of 2 received durvalumab 1500 mg every 28 days until progression or unacceptable toxicity.

Effects of provision of drinking water on the behavior and growth rate of group-housed calves with different milk allowances.

Despite the clear importance of drinking water, calves are not always provided water on farm for the first few weeks of life. The main objective of this study was to investigate the effects of water provision (access or no access) and milk allowance (high or low) on the behavior and growth rate of calves. Fifty mixed-breed calves were each assigned to 1 of 4 treatments: (1) water and high (10 L/d) milk allowance (n = 13), (2) no water and high milk allowance (n = 12), (3) water and low (5 L/d) milk allowance (n = 12), or (4) no water and low milk allowance (n = 13).

Can Isoflurane and Meloxicam Mitigate Pain Associated with Cautery Disbudding of 3-Week-Old Goat Kids?

We evaluated the effect of pain mitigation strategies (isoflurane and meloxicam) on the behaviour and physiology of 3-week-old disbudded goat kids. Fifty Saanen does (mean ± SD, 21 ± 3 days old) were randomly allocated to one of five treatments: (1) cautery-disbudded (CAUT), (2) CAUT + isoflurane (ISO), (3) CAUT + isoflurane + meloxicam (ISO+MEL), (4) CAUT + meloxicam (MEL), and (5) handled without disbudding or pain relief (SHAM). Blood samples were taken immediately prior to treatment and at 15-, 60- and 120-min post-treatment to assess cortisol, glucose and lactate concentrations.

Automated Collection and Analysis of Infrared Thermograms for Measuring Eye and Cheek Temperatures in Calves.

As the reliance upon automated systems in the livestock industry increases, technologies need to be developed which can be incorporated into these systems to monitor animal health and welfare. Infrared thermography (IRT) is one such technology that has been used for monitoring animal health and welfare and, through automation, has the potential to be integrated into automated systems on-farm. This study reports on an automated system for collecting thermal infrared images of calves and on the development and validation of an algorithm capable of automatically detecting and analysing the eye and cheek regions from those images.

Infrared Thermography-A Non-Invasive Method of Measuring Respiration Rate in Calves.

Respiration rate (RR) is a common measure of cattle health and welfare. Traditionally, measuring RR involves counting flank movements as the animal inhales and exhales with each breath. This method is often considered difficult, labour-intensive and impractical.

Physiological and behavioral responses as indicators for early disease detection in dairy calves.

This study investigated physiological and behavioral responses associated with the onset of neonatal calf diarrhea (NCD) in calves experimentally infected with rotavirus and assessed the suitability of these responses as early disease indicators. The suitability of infrared thermography (IRT) as a noninvasive, automated method for early disease detection was also assessed. Forty-three calves either (1) were experimentally infected with rotavirus (n = 20) or (2) acted as uninfected controls (n = 23).

Increasing predation risk with light reduces speed, exploration and visit duration of invasive ship rats (Rattus rattus).

Exploiting predation cues to deter pests remains an untapped management tool for conservationists. We examined foraging and movement patterns of 20 wild ship rats (Rattus rattus) within a large, outdoor 'U maze' that was either illuminated or dark to assess if light (an indirect predation cue) could deter rodents from ecologically vulnerable locations. Light did not alter rats' foraging behaviour (latency to approach seed tray, visits to seed tray, time per visit to seed tray, total foraging duration, foraging rate) within the experimental resource patch but three of seven movement behaviours were significantly impaired (53% fewer visits to the maze, 70% less exploration within the maze, 40% slower movement within the maze).

The effectiveness of clove oil and two different cautery disbudding methods on preventing horn growth in dairy goat kids.

The effectiveness of clove oil and cautery disbudding on horn growth was evaluated in goat kids. The study used 243 Saanen doe kids (4±1 days old; mean±SD) on two goat farms that were disbudded with either (i) clove oil injection (CLOVE), (ii) a cautery iron and bud removed (BUDOFF), or (iii) a cautery iron with bud left intact (BUDON). Each kid received a different treatment per bud, which were balanced between buds (left/right) and randomly allocated.

Pain sensitivity and injury associated with three methods of disbudding goat kids: Cautery, cryosurgical and caustic paste.

Pain sensitivity and skull/brain injury associated with cautery, cryosurgical and caustic paste disbudding were evaluated in goat kids. Kids (reared for meat; n=280) were randomly assigned to one of four treatments (n=70 per treatment): (1) sham-handling (SHAM) or (2) cautery (CAUT), (3) cryosurgical (CRYO) or (4) caustic paste (CASP) disbudding. A pain sensitivity test was carried out 15min pre-treatment and 1h post-treatment.

Measurement of dairy calf behavior prior to onset of clinical disease and in response to disbudding using automated calf feeders and accelerometers.

We determined if feeding and lying behavior, recorded by automatic calf feeding systems (ACFS) and accelerometers, could be used to detect changes in behavior before onset of neonatal calf diarrhea (NCD) or in response to disbudding pain in dairy calves. At 4 d of age, 112 calves had accelerometers attached to their hind leg and were housed in pens with ACFS. Calves were examined daily for signs of illness or injury.

Evaluation of alternatives to cautery disbudding of dairy goat kids using physiological measures of immediate and longer-term pain.

We evaluated alternatives to cautery disbudding of goat kids using physiological measures of immediate and longer-term pain. Fifty Saanen doe kids were randomly assigned to 1 of 5 treatments (n = 10/treatment): (1) cautery disbudding (CAUT), (2) caustic paste disbudding (CASP), (3) liquid nitrogen disbudding (CRYO), (4) clove oil injected into the horn bud (CLOV), or (5) sham disbudding (SHAM). Serum cortisol and haptoglobin concentrations were measured from blood samples collected immediately before treatment (baseline) and at 15, 30, 60, and 120 min and then again at 6 and 24 h post-treatment.

Photons and foraging: Artificial light at night generates avoidance behaviour in male, but not female, New Zealand weta.

Avoiding foraging under increased predation risk is a common anti-predator behaviour. Using artificial light to amplify predation risk at ecologically valuable sites has been proposed to deter introduced mice (Mus musculus) and ship rats (Rattus rattus) from degrading biodiversity in island ecosystems. However, light may adversely affect native species; in particular, little is known about invertebrate responses to altered lighting regimes.

Effect of isoflurane alone or in combination with meloxicam on the behavior and physiology of goat kids following cautery disbudding.

Cautery disbudding of goat kids is painful, but may be alleviated with pain mitigation. We therefore evaluated the effect of administering general anesthesia (isoflurane) or a nonsteroidal anti-inflammatory drug (meloxicam) on goat kid behavior and physiology following cautery disbudding. Trial 1 (n = 12/treatment) evaluated behavioral responses in 72 female Saanen dairy goat kids (mean ± standard error of the mean; 3.

Neural Basis of Ventromedial Hypothalamic Oxytocin-Driven Decrease in Appetite.

Objectives: Oxytocin (OT) administration in the ventromedial hypothalamic nucleus (VMH) reduces chow intake. The nature of VMH OT's anorexigenic action remains unclear. Here we provide insight into neural mechanisms underlying VMH OT-driven anorexia by (a) identifying feeding-related brain sites activated by VMH OT injection; (b) measuring VMH OT receptor (OTr) mRNA changes in response to hunger and palatability; and (c) examining how VMH OT affects episodic sweet solution intake in sated and hungry rats.

Oxytocin Acting in the Nucleus Accumbens Core Decreases Food Intake.

Central oxytocin (OT) promotes feeding termination in response to homeostatic challenges, such as excessive stomach distension, salt loading and toxicity. OT has also been proposed to affect feeding reward by decreasing the consumption of palatable carbohydrates and sweet tastants. Because the OT receptor (OTR) is expressed in the nucleus accumbens core (AcbC) and shell (AcbSh), a site regulating diverse aspects of eating behaviour, we investigated whether OT acts there to affect appetite in rats.

Converting Predation Cues into Conservation Tools: The Effect of Light on Mouse Foraging Behaviour.

Prey face a conflict between acquiring energy and avoiding predators and use both direct and indirect cues to assess predation risk. Illumination, an indirect cue, influences nocturnal rodent foraging behaviour. New Zealand holds no native rodent species but has introduced mice (Mus musculus) that severely impair native biodiversity.

Isotope effects, dynamic matching, and solvent dynamics in a Wittig reaction. Betaines as bypassed intermediates.

The mechanism of the Wittig reaction of anisaldehyde with a stabilized ylide was studied by a combination of (13)C kinetic isotope effects, conventional calculations, and molecular dynamics calculations in a cluster of 53 THF molecules. The isotope effects support a cycloaddition mechanism involving two sequential transition states associated with separate C-C and P-O bond formations. However, the betaine structure in between the two transition states is bypassed as an equilibrated intermediate in most trajectories.

Oxytocin receptor blockade reduces acquisition but not retrieval of taste aversion and blunts responsiveness of amygdala neurons to an aversive stimulus.

When gastrointestinal sickness induced by toxin injection is associated with exposure to novel food, the animal acquires a conditioned taste aversion (CTA). Malaise is accompanied by a surge in oxytocin release and in oxytocin neuronal activity; however, it is unclear whether oxytocin is a key facilitator of aversion or merely its marker. Herein we investigated whether blockade of the oxytocin receptor with the blood-brain barrier penetrant oxytocin receptor antagonist L-368,899 is detrimental for the acquisition and/or retrieval of lithium chloride (LiCl)-dependent CTA to a saccharin solution in mice.

Effect of previous handling experiences on responses of dairy calves to routine husbandry procedures.

The nature of human-animal interactions is an important factor contributing to animal welfare and productivity. Reducing stress during routine husbandry procedures is likely to improve animal welfare. We examined how the type of early handling of calves affected responses to two common husbandry procedures, ear-tagging and disbudding.

Effects of population size on singing behavior of a rare duetting songbird.

Although the genetic and ecological effects of population declines in endangered species have been well studied, little is known of the social consequences. Changes in signaling behavior may result in disrupted communication and affect both reproductive and conflict-resolution activities. The North Island Kōkako (Callaeas wilsoni) is an endangered, duetting (i.

Motivation to obtain a food reward of pregnant ewes in negative energy balance: behavioural, metabolic and endocrine considerations.

Low food availability often coincides with pregnancy in grazing animals. This study investigated how chronic reductions in food intake affected feeding motivation, and metabolic and endocrine parameters in pregnant sheep, which might be indicative of compromised welfare. Ewes with an initial Body Condition Score of 2.

Reduced cortisol and metabolic responses of thin ewes to an acute cold challenge in mid-pregnancy: implications for animal physiology and welfare.

Background: Low food availability leading to reductions in Body Condition Score (BCS; 0 indicates emaciation and 5 obesity) in sheep often coincides with low temperatures associated with the onset of winter in New Zealand. The ability to adapt to reductions in environmental temperature may be impaired in animals with low BCS, in particular during pregnancy when metabolic demand is higher. Here we assess whether BCS affects a pregnant animal's ability to cope with cold challenges.

Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study.

This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD.