bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives of animal welfare at farm and group level: Introduction and overview
Authors: Winckler C , Baumgartner J , Waiblinger S
Published: January 2023

If we are to bring about improvements in animal welfare, animal welfare assessment is the first step towards sustainable improvements, followed by the identification of risk factors and subsequent interventions. Largely driven by an increased public interest, which is accompanied by political strategies such as the Community Action Plan on the Protection and Welfare of Animals 2006-2010 (Commission of the EC 2006), the science of animal welfare assessment has developed considerably since the 1st International Workshop on Assessment of Animal Welfare at Farm and Group level held in 1999 in Copenhagen (Sørensen & Sandøe 2001). This is reflected in major research initiatives at national and international level and in the continuously increasing number of participants at the workshops.
Normal behaviour as a basis for animal welfare assessment
Authors: Wechsler B
Published: January 2023

It is generally agreed that farm animal welfare is at a high level when the animals can behave naturally. Most of today's housing systems, however, differ considerably from the natural environment in which the behavioural organisation of the ancestors of our farm animal species evolved. Consequently, normal behaviour may be impaired in several ways. Frequency, duration or sequence of behavioural elements may be affected. Some normal behaviour patterns may not occur at all. The animals may also possibly behave in unnatural ways – in patterns that would never occur in nature. Furthermore, it is usual for farm animals to exhibit behaviour which is normal in form, but which is elicited by artificial structures within their housing system.

In view of these possible changes in normal behaviour, it is necessary to assess, for each farm animal species and each housing system, whether animal welfare is at risk in any way if the behaviour observed differs from the behaviour that would occur in a natural environment. In some cases the question can be answered by taking a theoretical evolutionary approach. In most cases, however, detailed knowledge about the behavioural organisation of the animals is necessary. Such knowledge is built up from animal motivation studies and investigations into the effect of environmental structures on animal behaviour.

A specific problem of on-farm animal welfare assessment is that there is often not enough time to collect sufficient data to make a judgement about the occurrence of normal behaviour. Resource-based assessment methods are appropriate as an alternative, provided that the resource standards used are based on evidence stemming from research into animal behaviour and motivation.
The journey to animal welfare improvement
Authors: Whay HR
Published: January 2023

The process of driving improvement in animal welfare has three stages: 1) assessment of animal welfare, 2) identification of the risk factors potentially leading to a compromise in animal welfare, and 3) interventions, in response to the risk factors, to bring about improvement in animal welfare. This process is applicable to animals farmed in commercial situations and for individual animals kept or worked in isolated environments. An impressive weight of knowledge has accumulated in the science of animal welfare assessment and this needs to be counterbalanced by development of mechanisms to actively improve welfare. In the case of animal welfare, interventions have to motivate the animal owner or carer to make changes to their own behaviour on behalf of a third party; the animal. This is a different situation from that described in the human health literature where interventions encourage people to take steps to improve their own well-being, thus benefiting themselves directly. The development of strategies to improve animal welfare require a multi-disciplinary approach including social scientists, psychologists and economists, however, the skills of animal welfare scientists are essential to ensure that interventions truly achieve improvements in animal welfare.
Human and animal behaviour in dairy buffalo at milking
Authors: Saltalamacchia F , Tripaldi C , Castellano A , Napolitano F , Musto M , De Rosa G
Published: January 2023

This study aims to investigate the relationship between human behaviour, buffalo behaviour and prevalence of oxytocin injection at milking. The research was carried out on 17 buffalo farms. On each farm the stockperson's behaviour toward the buffaloes and the buffaloes' behaviour were observed during one afternoon's milking. Stockperson's behaviour was observed from collection of the animals in the waiting area to exit from the milking parlour. The following variables were recorded: number of positive, neutral and negative interactions. The number of steps and kicks were recorded from the entrance to the milking parlour to the removal of cups whenever the stockperson was less than 0.5 m from the animal. The prevalence of oxytocin injection at milking was recorded on two separate occasions with a 5-month interval to obtain a measure of the long-term consistency of this variable. Significant correlations were found between stepping and kicking, stepping and prevalence of oxytocin injection, kicking and prevalence of oxytocin injection and stockperson positive interactions and kicking. These results indicate that stockperson behaviour is related to buffalo behaviour at milking and the latter to the use of oxytocin injections. In addition, prevalence of oxytocin injection proved to be highly reliable when re-tested five months later.
Development of on-farm methods to assess the animal-human relationship in laying hens kept in non-cage systems
Authors: Raubek J , Niebuhr K , Waiblinger S
Published: January 2023

The aim of this study was to develop a set of tests to assess the reaction of laying hens towards humans in non-cage systems and to investigate the repeatability within and between days.

Based on a literature survey six tests were developed or modified, which were examined for practicability and adapted in a first phase. Reactions of hens were recorded directly or with a video camera. These included the reaction towards a stationary person: stockperson (SPs); experimenter: (SPe); a moving person: (moving through flock [MP]; approaching individual hens measuring avoidance distance [AD]) and a complex test including stationary and moving elements: (arm moving to touch hens [touch test] in the litter [Tl] and on the slatted area [Ts]). Six flocks of five farms were visited twice, one week apart. At each visit the six tests were performed during morning and afternoon hours. The order of the tests differed between farms.

Repeatability of flock reactions within as well as between days was high for SPs, AD and Tl. SPe and especially MP showed slightly reduced correlations. Touching hens at the droppings pit (Ts) was less repeatable than in the litter area (Tl).

To sum up, first experiences show that most tests can be practically used in groups of hens in non-cage systems and seem to have good repeatability.
Repeatability of a skin tent test for dehydration in working horses and donkeys
Authors: Pritchard JC , Barr ARS , Whay HR
Published: January 2023

Dehydration is a serious welfare issue for equines working in developing countries. Risk factors such as high ambient temperature, heavy workload and poor water availability are exacerbated by the traditional belief that provision of water to working animals will reduce their strength or cause colic and muscle cramps.

As part of the welfare assessment of 4889 working horses and donkeys during 2002/3, eight observers were trained to perform a standardised skin tent test. The prevalence of a prolonged duration of skin tenting was 50% in horses and 37% in donkeys. Two studies investigated inter-observer repeatability of skin tent test techniques, using a total of 220 horses and donkeys in India and then Egypt: measures of agreement with a ‘gold standard’ observer varied from 40 to 99%. Simplifying the test by reducing the number of possible scores for skin tent from three (immediate return of skin to normal position; delayed return up to three seconds; delayed return more than three seconds) to two (immediate return of skin to normal position; delayed return of any duration) did not improve overall repeatability of the skin tent test. Potential reasons for not achieving high levels of agreement include variations in assessment method, assessors' previous experience, subjective demarcation between score categories and biological variability.
Welfare assessment in extensive animal production systems: challenges and opportunities
Authors: Turner SP , Dwyer CM
Published: January 2023

The welfare of animals in extensive systems has received little attention despite significant welfare challenges in these environments. Additionally, recent reform of Common Agricultural Policy payments in the EU have put increasing financial emphasis on farmers to attain improved levels of animal welfare, although suitable methodologies for assessing animal welfare are lacking. Assessment of welfare in intensive systems frequently involves assessing compliance with buildings and space requirements, as well as behavioural observations of animals in their home pens and monitoring of health records. In extensive systems, however, many of these measures are inappropriate or impossible. Environments are often heterogeneous, animals may be difficult to observe, individuals may not be identifiable and health records may be limited or completely lacking. The expression of fear by extensive animals, which rarely come into close contact with humans, often limits the value and practicality of behavioural observations as welfare indicators. Currently, welfare audits of extensive farms rely greatly on mortality and morbidity records to determine welfare status. Whilst these measures are important, the strong health monitoring bias does not adequately allow an interpretation of the emotional experiences of extensive animals. We suggest that developing methodologies based on assessing key features of the environment, such as handling facilities, assessment of the skills, knowledge and planning of the stockperson, and assessing the animal at key points in the production cycle when they are gathered may allow a workable methodology for assessing animal welfare to be developed for extensive systems.
Evaluation of a welfare indicator protocol for assessing animal welfare in AMS herds: researcher, production advisor and veterinary practitioner opinion
Authors: Rousing T , Jakobsen IA , Hindhede J , Klaas IC , Bonde M , Sørensen JT
Published: January 2023

A welfare indicator protocol integrating a total of 38 measures from 4 information sources: housing system, management, animal behaviour and clinical health has been developed for decision support in Automatic Milking System (AMS) herds. Two expert opinion studies focusing on the relevance of the welfare indicator protocol as basis for on-farm welfare assessment have been carried out; one study focused on the opinion of 21 AMS researchers; the other on that of 14 AMS production advisors and 15 veterinary practitioners. The researchers were asked to score the individual welfare relevance of the 38 measures. Furthermore, both the panels were asked to prioritise the 10 most important measures. The 21 researchers generally appreciated the listed protocol measures as highly relevant. The researcher and advisor panels agreed on prioritised measures from all 4 information sources among the 10 most important welfare indicators. In summary, researchers as well as production advisors and veterinarians supported the suggested measures for inclusion in a welfare assessment system. This has demonstrated that integration of different information is considered decisive for operational welfare assessment at herd level.
On-farm welfare assessment systems: what are the recording costs?
Authors: Sørensen JT , Rousing T , Møller SH , Bonde M , Hegelund L
Published: January 2023

To illustrate that different approaches lead to different costs a cost calculation on four different welfare assessment systems for four different animal species has been carried out; an integrated pig herd (450 sows), a dairy cattle herd with automatic milking (90 cows), an organic egg production system (3000 layers) and a mink farm (1000 mink). We calculated the cost to be: €375 per annum for the mink farm and €2205, €2430 and €2435 for the egg production system, the AMS dairy herd and the integrated pig farm, respectively. The costs can be reduced by: reducing the number of indicators and/or the recording frequency, reducing sample sizes, more intensive use of existing data and by exchanging external for internal recordings.
‘Animal Ethics Dilemma’: an interactive learning tool for university and professional training
Authors: Hanlon AJ , Algers A , Dich T , Hansen T , Loor H , Sandøe P
Published: January 2023

‘Animal Ethics Dilemma’ is a freely available computer-supported learning tool (www.animalethicsdilemma.net or www.aedilemma.net) which has been developed primarily for veterinary undergraduates but is applicable also to students in other fields of animal science. The objectives of the computer program are to promote students' understanding of the ethics related to animal use, to illustrate ethical dilemmas that arise in animal use, to broaden students' moral imagination, and to enable students to differentiate between types of ethical argument. The program comprises five case studies: (1) the blind hens; (2) ANDi the genetically modified monkey; (3) euthanasia of a healthy dog; (4) animal slaughter; and (5) rehabilitation of seals. Special consideration has been given to enhancing the pedagogic value of the program. Students can control their learning by selecting a variety of ways to explore the program; for example, they can navigate the program using the ‘Assist Me’ option, which explains the basis of the ethical arguments. Reality text provides details of real events on which the case is based, and a glossary of terminology is available for the students to explore. Selected access to a case template is also available, enabling students and teachers to create their own case studies. Evaluation of the program has been ongoing during its development.
Welfare and mate choice in zebra finches: effect of handling regime and presence of cover
Authors: Collins SA , Archer JA , Barnard CJ
Published: January 2023

Much attention has been focused, quite rightly, on the welfare of laboratory rodents and farm animals but certain other groups have been less well represented in welfare research. Small birds, for example, are often kept as pets and used in a wide variety of behavioural and physiological experiments where ‘best’ housing conditions are based on advice from experienced keepers as opposed to being tested experimentally. We investigated the effects of two husbandry conditions on the welfare of captive zebra finches: a) optional cover and b) rewarded handling versus random rewards. As a correlate of welfare in the four conditions (cover + reward, cover, reward, nothing), we recorded the time to settle and perform normal behaviours after an experimenter entered the room throughout the study (ie habituation to disturbance). In addition, we measured female preference for males in the four conditions to see whether welfare situation affected attractiveness as a mate. Birds in the two conditions where a reward was provided settled most quickly; and their settling time decreased across the study. Birds provided with cover alone became more disturbed by the entry of the experimenter as the study progressed. However, the birds taking longest on average to settle were those in cages with no cover and no reward. Females preferred males in the reward conditions as mates, either due to the fact that these males settled more quickly or because less-stressed males are more attractive in some other way. Thus, rewarding birds after disturbance is an effective and simple way to improve habituation to handling and human presence. In addition, these birds are more attractive to females, implying that males more habituated to captivity may be preferred as mates. Provision of cover may help under certain circumstances, but appears paradoxically to lead to increased fearfulness over time under the conditions studied here.
The effect of pen size and an enrichment structure (elevated platform) on the performances and the behaviour of fattening rabbits
Authors: Postollec G , Boilletot E , Maurice R , Michel V
Published: January 2023

The effects of a (30 cm high) elevated platform as an enrichment structure on the behaviour and performance of fattening rabbits kept in groups were investigated. Three housing systems for fattening rabbits were compared using a stocking density of 15 rabbits m–2. The rabbits were housed either in large pens (3.67 m2plus a platform of 0.39 m2; with 60 rabbits per pen) or in small pens (0.503 m2plus a platform of 0.159 m2; with10 rabbits per pen), or in conventional standard cages (0.39 m2, with 6 rabbits and without any enrichment) from 31 to 72 days of age. The conventional cages without a platform were used as a control and reference model. Rabbits housed in each small pen or in each cage belonged to the same litter, and the 60 rabbits sharing the same large pen were from six or seven litters. At the end of fattening, rabbits reached the weight of 2,508 g in cages, 2,397 g in small pens, and 2,340 g in large pens; the only significant difference was daily weight gain which was better in cages than in both pens. There was no difference in growth parameters between the two types of pens. The mortality rate was less than 1% for all treatments. No sanitation problems or severe lesions were seen with rabbits even those reared in large pens and large groups. Neither housing systems, nor elevated platform affected activities such as dietary intake or resting. The use of the platform appears to depend upon the amount of space available; in a large pen, an elevated platform can be utilised as an exercise structure while in a small pen it was used more as simply extra space to occupy.
Post-release survival of hand-reared tawny owls (Strix aluco) based on radio-tracking and leg-band return data
Authors: Leighton K , Chilvers D , Charles A , Kelly A
Published: January 2023

The post-release survival of hand-reared tawny owls(Strix aluco)was measured using radio-tracking and leg-band return data. Of 16 birds fitted with 2.4 g radiotelemetry tags, two shed their tags after four and nine days, respectively and one bird was recovered and the tag removed. The remaining 13 birds were tracked for between 16 and 84 days (median 38). Of these, two were found dead (one emaciated and one predated) and one was recovered alive but emaciated and was subsequently euthanased. Thirty-seven percent were radio-tracked for more than six weeks, thought to be the critical period beyond which raptors will mostly survive. Of 112 birds banded between 1995 and 2005, 18 were recovered (seven live and 11 dead). Of the seven live recoveries, three were involved in road traffic collisions. Of the dead recoveries for which the cause of death was known (n = 4), all had been involved in road traffic collisions. The time elapsed between release and recovery ranged from 1–2,246 days (median 123 days). Over 65% survived for more than six weeks. The distance travelled between release and recovery ranged between 0 and 6 km (median 0). Further work is required on the effects of hand rearing on post-release survival of rehabilitated wildlife.
Perioperative stress response in dogs undergoing elective surgery: variations in behavioural, neuroendocrine, immune and acute phase responses
Authors: Siracusa C , Manteca X , Cerón J , Martínez-Subiela S , Cuenca R , Lavín S , Garcia F , Pastor J
Published: January 2023

The aim of this trial was to describe the behavioural, neuroendocrine, immune and acute phase stress responses in dogs undergoing elective surgery in normal, clinical practice conditions. Sixteen dogs were submitted to elective orchiectomy or ovariohysterectomy using a standardised surgical protocol. Each animal was confined to the Intensive Care Unit during pre- and post-surgery and perioperative behavioural, neuroendocrine, immune and acute phase responses were studied. Behavioural categories, cortisol, prolactin, white blood cell, C-reactive protein and haptoglobin variation were evaluated. Values at different times were compared with basal values shown by the dog in its usual environment. Communicative and explorative behaviours showed high occurrence pre-surgery and were inhibited post-surgery. Decreases in post-surgery activity, interactive behaviours and changes in waking/sleeping patterns were observed. The most sensitive marker of psychological stress, cortisol, in comparison with basal values, showed a significant increase both during pre- and post-surgery confinement in the ICU cage. Prolactin values were characterised by a significant decrease early into the post-surgery period. The immune response was characterised by long-term neutrophilia and monocytosis, but by short-term lymphopaenia and eosinopaenia, limited to the early post-operative period. With regard to the acute phase response, both C-reactive protein and haptoglobin showed a long-term increase, post-surgery. Changes in behavioural, haematological and biochemical markers showed that perioperative stress represents a major challenge to dog welfare.
Welfare assessment of captive Asian elephants (Elephas maximus) and Indian rhinoceros (Rhinoceros unicornis) using salivary cortisol measurement
Authors: Menargues A , Urios V , Mauri M
Published: January 2023

The measurement of salivary cortisol allows non-invasive assessment of welfare in captive animals. We utilised this technique to test the effect of zoo opening on six Asian elephants and two Indian rhinoceros at the Terra Natura Zoological Park, Alicante, Spain, during pre-opening, opening and post-opening periods. Salivary cortisol concentrations were found to be significantly higher during the opening period than during pre- and post-opening periods for both species. This method could prove a useful tool in monitoring the success of decisions taken to improve the welfare of captive animals.
Preferences of Housed Finishing Beef Cattle for Different Floor Types
Authors: Lowe D E , Steen R W J , Beattie V E
Published: January 2023

Six pairs of steers were allowed to choose between two types of floors in a paired choice test. The four floors tested were a fully slatted floor, a fully slatted floor covered with rubber mats, a solid floor with sawdust bedding, and a solid floor with straw bedding. All combinations of floor types were tested and the choices were repeated eight times, using naïve animals. The animals were allowed 17 days to habituate, and on days 18-21 their behaviour was recorded by video for 72 hours. Straw was the most preferred floor type, followed by sawdust, then mats, and finally slats. During a second test period, rubber mats were compared with rubber strips, and no significant preferences were found.
Improving the Implementation of Advance Directives in Spain
Authors: Herreros Benjamín , Gella Pablo , Valenti Emanuele , Márquez Octavio , Moreno Beatriz , Velasco Tayra
Published: January 2023

Since 2002, legislation in Spain has allowed for the creation and documentation of end-of-life decisionmaking. Over the intervening years, the actual implementation of such documents is very low. Through extensive analysis of the literature, this article explores the current status of the use of and attitudes toward advance directives in Spain and then proposes strategies for improvement in their implementation.
On the Replicability of Data Collection Using Online News Databases
Authors: Karstens Mikaela , Soules Michael J. , Dietrich Nick
Published: January 2023

News databases, such as Factiva and Nexis Uni, are vital for the construction of many commonly used datasets of political events because they provide researchers with access to thousands of diverse news sources. This article raises several issues with news databases that pose a threat to the quality and replicability of data-collection efforts. We recommend best practices for using news databases to gather event data.
ADAM SMITH AND THE WEALTH-WORSHIPPING SPECTATOR
Authors: Elazar Yiftah
Published: January 2023

What explains the ambition to get rich? Adam Smith is clear that commercial ambition, the passionate desire for great wealth, is not simply a desire to satisfy one’s material needs. His argument on what underlies it, however, is not obvious. I review three possibilities suggested by Smith’s work and the scholarly literature—vanity, the love of system, and the desire for tranquility—and conclude that none of them captures the underlying motive of commercial ambition. Instead, I argue that Smith understands commercial ambition as a misguided desire for excellence. Ambitious pursuers of wealth are driven by the desire to deserve and to enjoy recognition for their excellence, but their judgment of what is truly excellent is corrupted by the standards of a wealth-worshipping society. Instead of appealing to the moral standpoint of the impartial spectator, they construct in their minds and follow a corruptive moral guide: the wealth-worshipping spectator.
‘Not a cure, but helpful’ – exploring the suitability of evidence-based psychological interventions to the needs of Black, Asian and Minority Ethnic (BAME) communities
Authors: Faheem Afsana
Published: January 2023

Individuals from Black, Asian and Minority Ethnic (BAME) groups experience profound disparities in accessing mental healthcare, show poorer treatment outcomes, and high attrition rates when compared to their White British counterparts. Despite the national rollout of Improving Access to Psychological Therapies (IAPT) services, research exploring service users’ recovery narrative has been scarce. The aim of this study was to explore whether evidence-based psychological interventions are suitable to the needs of BAME communities. Semi-structured interviews were conducted with nine BAME service users who received evidence-based psychological treatment(s) from IAPT services. Reflexive thematic analysis (RTA) was used to analyse the data which included a six-phase process to produce a robust pattern-based analysis. Overall, three themes were generated. The first theme highlighted the importance of recognising cultural dissonance within therapy, which considered patient therapeutic expectations, therapeutic guilt, and conflicting cultural identities. The second theme identified the need for therapists to develop cultural competency. This included the importance of building therapeutic trust and exploration of patient culture within therapy. The final theme considered the road to recovery and highlighted challenges with therapeutic engagement and evaluations of therapeutic effectiveness. Overall, BAME service users felt that therapy was not a cure, but found it helpful. Clinical implications and future recommendations are discussed.

Key learning aims

(1)

To briefly introduce cross-cultural theoretical models that may assist mental health professionals to think critically about whether Western notions of therapy are suited to the needs of ethnic minority communities.

(2)

To highlight cultural challenges that may impede therapeutic success for BAME communities.

(3)

For IAPT services and practitioners to consider cultural competency training needs that may enhance service user therapeutic experiences and outcomes.

(4)

To encourage IAPT services to enhance knowledge about psychotherapy and mental health by promoting culturally sensitive psychoeducation in ethnic minority communities.
Physics‐Based Approach to Thermospheric Density Estimation Using CubeSat GPS Data
Authors: Mutschler Shaylah M. , Axelrad Penina , Sutton Eric K. , Masters Dallas
Published: January 2023

In Low Earth Orbit (LEO), atmospheric drag is the largest contributor to trajectory prediction error. The current thermospheric density model used in operations, the High Accuracy Satellite Drag Model (HASDM), applies corrections to an empirical density model every 3 hr using observations of 75+ calibration satellites. This work aims to improve global thermospheric density estimation by utilizing a physics‐based space environment model and precise GPS‐based orbit estimates of LEO CubeSats. The data assimilation approach presented here estimates drivers of the Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model (TIE‐GCM) every 1.5 hr using CubeSat GPS information. In this work, Spire Global CubeSat data are used to demonstrate the method using only 10 satellites; the true strength of the method is its potential to exploit data already collected on large LEO constellations (hundreds of CubeSats). Precise Orbit Determination (POD) information from 10 CubeSats over 12 days is used to sense a global density field when Kp historical data show a minor and moderate geomagnetic storm in succession. This paper provides a direct comparison of estimated density, derived by our new method, to HASDM and Swarm mission derived density. A propagation analysis is also executed by comparing the CubeSat POD data to orbits propagated using our estimated density versus HASDM density. The analyses show that the estimated density is within 35% of HASDM during storm‐time conditions, and that the propagation using the estimated density yields an improvement of 26% over NRLMSISE‐00 compared to HASDM, while outperforming HASDM during the second storm peak.
Structure and Seasonal Variability of the Arctic Boundary Current North of Severnaya Zemlya
Authors: Ruiz‐Castillo Eugenio , Janout Markus , Hölemann Jens , Kanzow Torsten , Schulz Kirstin , Ivanov Vladimir
Published: January 2023

We assessed the spatial and temporal variability of the Arctic Boundary Current (ABC) using seven oceanographic moorings, deployed across the continental slope north of Severnaya Zemlya in 2015–2018. Transports and individual water masses were quantified based on temperature and salinity recorders and current profilers. Our results were compared with observations from the northeast Svalbard and the central Laptev Sea continental slopes to evaluate the hydrographic transformation along the ABC pathway. The highest velocities (>0.30 m s−1) of the ABC occurred at the upper continental slope and decreased offshore to below 0.03 m s−1 in the deep basin. The ABC showed seasonal variability with velocities two times higher in winter than in summer. Compared to upstream conditions in Svalbard, water mass distribution changed significantly within 20 km of the shelf edge due to mixing with‐ and intrusion of shelf waters. The ABC transported 4.15 ± 0.3 Sv in the depth range 50–1,000 m, where 0.88 ± 0.1, 1.5 ± 0.2, 0.61 ± 0.1 and 1.0 ± 0.15 Sv corresponded to Atlantic Water (AW), Dense Atlantic Water (DAW), Barents Sea Branch Water (BSBW) and Transformed Atlantic Water (TAW). 62–70% of transport was constrained to within 30–40 km of the shelf edge, and beyond 84 km, transport increases were estimated to be 0.54 Sv. Seasonality of TAW derived from local shelf‐processes and advection of seasonal‐variable Fram Strait waters, while BSBW transport variability was dominated by temperature changes with maximum transport coinciding with minimum temperatures. Further Barents Sea warming will likely reduce TAW and BSBW transport leading to warmer conditions along the ABC pathway.
Dinitrogen Emissions Dominate Nitrogen Gas Emissions From Soils With Low Oxygen Availability in a Moist Tropical Forest
Authors: Almaraz Maya , Groffman Peter M. , Silver Whendee L. , Hall Steven J. , Lin Yang , O’Connell Christine , Porder Stephen
Published: January 2023

Lowland tropical forest soils are relatively N rich and are the largest global source of N2O (a powerful greenhouse gas) to the atmosphere. Despite the importance of tropical N cycling, there have been few direct measurements of N2 (an inert gas that can serve as an alternate fate for N2O) in tropical soils, limiting our ability to characterize N budgets, manage soils to reduce N2O production, or predict the future role that N limitation to primary productivity will play in buffering against climate change. We collected soils from across macro‐ and micro‐topographic gradients that have previously been shown to differ in O2 availability and trace gas emissions. We then incubated these soils under oxic and anoxic headspaces to explore the relative effect of soil location versus transient redox conditions. No matter where the soils came from, or what headspace O2 was used in the incubation, N2 emissions dominated the flux of N gas losses. In the macrotopography plots, production of N2 and N2O were higher in low O2 valleys than on more aerated ridges and slopes. In the microtopography plots, N2 emissions from plots with lower mean soil O2 (5%–10%) were greater than in plots with higher mean soil O2 (10%–20%). We estimate an N gas flux of ∼37 kg N/ha/yr from this forest, 99% as N2. These results suggest that N2 fluxes may have been systematically underestimated in these landscapes, and that the measurements we present call for a reevaluation of the N budgets in lowland tropical forest ecosystems.
Increased cross-presentation by dendritic cells and enhanced anti-tumour therapy using the Arp2/3 inhibitor CK666
Authors: Oliveira Mariana M. S. , D’Aulerio Roberta , Yong Tracer , He Minghui , Baptista Marisa A. P. , Nylén Susanne , Westerberg Lisa S.
Published: January 2023

Background

Dendritic cell (DC) vaccines for cancer therapy offer the possibility to let the patient’s own immune system kill cancer cells. However, DC vaccines have shown less efficacy than expected due to failure to induce cancer cell killing and by activating T regulatory cells.

Methods

We tested if inhibition of signalling via WASp and Arp2/3 using the small molecule CK666 would enhance DC-mediated killing of tumour cells in vitro and in vivo.

Results

Using CK666 during the ex vivo phase of antigen processing of ovalbumin (OVA), murine and human DCs showed decreased phagosomal acidification, indicating activation of the cross-presentation pathway. When compared to untreated DCs, DCs treated with CK666 during uptake and processing of OVA-induced increased proliferation of OVA-specific CD8+ OT-I T cells in vitro and in vivo. Using the aggressive B16-mOVA melanoma tumour model, we show that mice injected with CK666-treated DCs and OVA-specific CD8+ OT-I T cells showed higher rejection of B16 melanoma cells when compared to mice receiving non-treated DCs. This resulted in the prolonged survival of tumour-bearing mice receiving CK666-treated DCs. Moreover, combining CK666-treated DCs with the checkpoint inhibitor anti-PD1 further prolonged survival.

Conclusion

Our data suggest that the small molecule inhibitor CK666 is a good candidate to enhance DC cross-presentation for cancer therapy.
TP73 Isoform-specific disruption reveals a critical role of TAp73beta in growth suppression and inflammatory response
Authors: Zhang Jin , Sun Wenqiang , Yan Wensheng , Kong Xiangmudong , Shen Tong , Laubach Kyra , Chen Mingyi , Chen Xinbin
Published: January 2023

TP73 is expressed as multiple N- and C-terminal isoforms through two separate promoters or alternative splicing. While N-terminal p73 isoforms have been well studied, very little is known about p73 C-terminal isoforms. Thus, CRISPR was used to delete TP73 Exon13 (E13-KO) to induce p73α to p73β isoform switch. We showed that E13-KO led to decreased cell proliferation and migration and sensitized cells to ferroptosis, which can be reverted by knockdown of TAp73β in E13-KO cells. To understand the biological function of p73β in vivo, we generated a mouse model in that the Trp73 E13 was deleted by CRISPR. We showed that p73α to p73β isoform switch led to increased cellular senescence in mouse embryonic fibroblasts. We also showed that E13-deficient mice exhibited shorter life span and were prone to spontaneous tumors, chronic inflammation and liver steatosis as compared to WT mice. Additionally, we found that the incidence of chronic inflammation and liver steatosis was higher in E13-deficient mice than that in Trp73-deficient mice, suggesting that p73β is a strong inducer of inflammatory response. Mechanistically, we showed that TAp73β was able to induce cysteine dioxygenase 1 (CDO-1), leading to cysteine depletion and subsequently, enhanced ferroptosis and growth suppression. Conversely, knockdown of CDO-1 was able to alleviate the growth suppression and ferroptosis in E13-KO cells. Together, our data suggest that at a physiologically relevant level, TAp73β is a strong inducer of growth suppression but insufficient to compensate for loss of TAp73α in tumor suppression due to aberrant induction of inflammatory response and liver steatosis.
Balancing the safeguarding of privacy and data sharing: perceptions of genomic professionals on patient genomic data ownership in Australia
Authors: Malakar Yuwan , Lacey Justine , Twine Natalie A. , McCrea Rod , Bauer Denis C.
Published: January 2023

There are inherent complexities and tensions in achieving a responsible balance between safeguarding patients’ privacy and sharing genomic data for advancing health and medical science. A growing body of literature suggests establishing patient genomic data ownership, enabled by blockchain technology, as one approach for managing these priorities. We conducted an online survey, applying a mixed methods approach to collect quantitative (using scale questions) and qualitative data (using open-ended questions). We explored the views of 117 genomic professionals (clinical geneticists, genetic counsellors, bioinformaticians, and researchers) towards patient data ownership in Australia. Data analysis revealed most professionals agreed that patients have rights to data ownership. However, there is a need for a clearer understanding of the nature and implications of data ownership in this context as genomic data often is subject to collective ownership (e.g., with family members and laboratories). This research finds that while the majority of genomic professionals acknowledge the desire for patient data ownership, bioinformaticians and researchers expressed more favourable views than clinical geneticists and genetic counsellors, suggesting that their views on this issue may be shaped by how closely they interact with patients as part of their professional duties. This research also confirms that stronger health system infrastructure is a prerequisite for enabling patient data ownership, which needs to be underpinned by appropriate digital infrastructure (e.g., central vs. decentralised data storage), patient identity ownership (e.g., limited vs. self-sovereign identity), and policy at both federal and state levels.
Preclinical evaluation of FLT190, a liver-directed AAV gene therapy for Fabry disease
Authors: Jeyakumar Jey M. , Kia Azadeh , Tam Lawrence C. S. , McIntosh Jenny , Spiewak Justyna , Mills Kevin , Heywood Wendy , Chisari Elisa , Castaldo Noemi , Verhoef Daniël , Hosseini Paniz , Kalcheva Petya , Cocita Clement , Miranda Carlos J. , Canavese Miriam , Khinder Jaminder , Rosales Cecilia , Hughes Derralynn , Sheridan Rose , Corbau Romuald , Nathwani Amit
Published: January 2023

Fabry disease is an X-linked lysosomal storage disorder caused by loss of alpha-galactosidase A (α-Gal A) activity and is characterized by progressive accumulation of glycosphingolipids in multiple cells and tissues. FLT190, an investigational gene therapy, is currently being evaluated in a Phase 1/2 clinical trial in patients with Fabry disease (NCT04040049). FLT190 consists of a potent, synthetic capsid (AAVS3) containing an expression cassette with a codon-optimized human GLA cDNA under the control of a liver-specific promoter FRE1 (AAV2/S3-FRE1-GLAco). For mouse studies FLT190 genome was pseudotyped with AAV8 for efficient transduction. Preclinical studies in a murine model of Fabry disease (Gla-deficient mice), and non-human primates (NHPs) showed dose-dependent increases in plasma α-Gal A with steady-state observed 2 weeks following a single intravenous dose. In Fabry mice, AAV8-FLT190 treatment resulted in clearance of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in plasma, urine, kidney, and heart; electron microscopy analyses confirmed reductions in storage inclusion bodies in kidney and heart. In NHPs, α-Gal A expression was consistent with the levels of hGLA mRNA in liver, and no FLT190-related toxicities or adverse events were observed. Taken together, these studies demonstrate preclinical proof-of-concept of liver-directed gene therapy with FLT190 for the treatment of Fabry disease.
Seasonal temperatures in West Antarctica during the Holocene
Authors: Jones Tyler R. , Cuffey Kurt M. , Roberts William H. G. , Markle Bradley R. , Steig Eric J. , Stevens C. Max , Valdes Paul J. , Fudge T. J. , Sigl Michael , Hughes Abigail G. , Morris Valerie , Vaughn Bruce H. , Garland Joshua , Vinther Bo M. , Rozmiarek Kevin S. , Brashear Chloe A. , White James W. C.
Published: January 2023

The recovery of long-term climate proxy records with seasonal resolution is rare because of natural smoothing processes, discontinuities and limitations in measurement resolution. Yet insolation forcing, a primary driver of multimillennial-scale climate change, acts through seasonal variations with direct impacts on seasonal climate1. Whether the sensitivity of seasonal climate to insolation matches theoretical predictions has not been assessed over long timescales. Here, we analyse a continuous record of water-isotope ratios from the West Antarctic Ice Sheet Divide ice core to reveal summer and winter temperature changes through the last 11,000 years. Summer temperatures in West Antarctica increased through the early-to-mid-Holocene, reached a peak 4,100 years ago and then decreased to the present. Climate model simulations show that these variations primarily reflect changes in maximum summer insolation, confirming the general connection between seasonal insolation and warming and demonstrating the importance of insolation intensity rather than seasonally integrated insolation or season duration2,3. Winter temperatures varied less overall, consistent with predictions from insolation forcing, but also fluctuated in the early Holocene, probably owing to changes in meridional heat transport. The magnitudes of summer and winter temperature changes constrain the lowering of the West Antarctic Ice Sheet surface since the early Holocene to less than 162 m and probably less than 58 m, consistent with geological constraints elsewhere in West Antarctica4–7.
An electric molecular motor
Authors: Zhang Long , Qiu Yunyan , Liu Wei-Guang , Chen Hongliang , Shen Dengke , Song Bo , Cai Kang , Wu Huang , Jiao Yang , Feng Yuanning , Seale James S. W. , Pezzato Cristian , Tian Jia , Tan Yu , Chen Xiao-Yang , Guo Qing-Hui , Stern Charlotte L. , Philp Douglas , Astumian R. Dean , Goddard William A. , Stoddart J. Fraser
Published: January 2023

Macroscopic electric motors continue to have a large impact on almost every aspect of modern society. Consequently, the effort towards developing molecular motors1–3 that can be driven by electricity could not be more timely. Here we describe an electric molecular motor based on a [3]catenane4,5, in which two cyclobis(paraquat-p-phenylene)6 (CBPQT4+) rings are powered by electricity in solution to circumrotate unidirectionally around a 50-membered loop. The constitution of the loop ensures that both rings undergo highly (85%) unidirectional movement under the guidance of a flashing energy ratchet7,8, whereas the interactions between the two rings give rise to a two-dimensional potential energy surface (PES) similar to that shown by FOF1 ATP synthase9. The unidirectionality is powered by an oscillating10 voltage11,12 or external modulation of the redox potential13. Initially, we focused our attention on the homologous [2]catenane, only to find that the kinetic asymmetry was insufficient to support unidirectional movement of the sole ring. Accordingly, we incorporated a second CBPQT4+ ring to provide further symmetry breaking by interactions between the two mobile rings. This demonstration of electrically driven continual circumrotatory motion of two rings around a loop in a [3]catenane is free from the production of waste products and represents an important step towards surface-bound14 electric molecular motors.
Financial incentives for vaccination do not have negative unintended consequences
Authors: Schneider Florian H. , Campos-Mercade Pol , Meier Stephan , Pope Devin , Wengström Erik , Meier Armando N.
Published: January 2023

Financial incentives to encourage healthy and prosocial behaviours often trigger initial behavioural change1–11, but a large academic literature warns against using them12–16. Critics warn that financial incentives can crowd out prosocial motivations and reduce perceived safety and trust, thereby reducing healthy behaviours when no payments are offered and eroding morals more generally17–24. Here we report findings from a large-scale, pre-registered study in Sweden that causally measures the unintended consequences of offering financial incentives for taking the first dose of a COVID-19 vaccine. We use a unique combination of random exposure to financial incentives, population-wide administrative vaccination records and rich survey data. We find no negative consequences of financial incentives; we can reject even small negative impacts of offering financial incentives on future vaccination uptake, morals, trust and perceived safety. In a complementary study, we find that informing US residents about the existence of state incentive programmes also has no negative consequences. Our findings inform not only the academic debate on financial incentives for behaviour change but also policy-makers who consider using financial incentives to change behaviour.
γδ T cells are effectors of immunotherapy in cancers with HLA class I defects
Authors: de Vries Natasja L. , van de Haar Joris , Veninga Vivien , Chalabi Myriam , Ijsselsteijn Marieke E. , van der Ploeg Manon , van den Bulk Jitske , Ruano Dina , van den Berg Jose G. , Haanen John B. , Zeverijn Laurien J. , Geurts Birgit S. , de Wit Gijs F. , Battaglia Thomas W. , Gelderblom Hans , Verheul Henk M. W. , Schumacher Ton N. , Wessels Lodewyk F. A. , Koning Frits , de Miranda Noel F. C. C. , Voest Emile E.
Published: January 2023

DNA mismatch repair-deficient (MMR-d) cancers present an abundance of neoantigens that is thought to explain their exceptional responsiveness to immune checkpoint blockade (ICB)1,2. Here, in contrast to other cancer types3–5, we observed that 20 out of 21 (95%) MMR-d cancers with genomic inactivation of β2-microglobulin (encoded by B2M) retained responsiveness to ICB, suggesting the involvement of immune effector cells other than CD8+ T cells in this context. We next identified a strong association between B2M inactivation and increased infiltration by γδ T cells in MMR-d cancers. These γδ T cells mainly comprised the Vδ1 and Vδ3 subsets, and expressed high levels of PD-1, other activation markers, including cytotoxic molecules, and a broad repertoire of killer-cell immunoglobulin-like receptors. In vitro, PD-1+ γδ T cells that were isolated from MMR-d colon cancers exhibited enhanced reactivity to human leukocyte antigen (HLA)-class-I-negative MMR-d colon cancer cell lines and B2M-knockout patient-derived tumour organoids compared with antigen-presentation-proficient cells. By comparing paired tumour samples from patients with MMR-d colon cancer that were obtained before and after dual PD-1 and CTLA-4 blockade, we found that immune checkpoint blockade substantially increased the frequency of γδ T cells in B2M-deficient cancers. Taken together, these data indicate that γδ T cells contribute to the response to immune checkpoint blockade in patients with HLA-class-I-negative MMR-d colon cancers, and underline the potential of γδ T cells in cancer immunotherapy.