Diffusion tensor imaging (DTI) is an imaging technique that uses magnetic resonance. It measures the diffusion of water molecules in tissues, which can occur either without restriction  or limited by some obstacles, such as cell membranes . Diffusion is most often measured in terms of, inter alia, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). DTI allows us to reconstruct, visualize, and evaluate certain qualities of white matter. To date, many studies have sought to associate various changes in the distribution of diffusion within the brain with mental diseases and disorders. A better understanding of white matter integrity disorders can help us recognize the causes of diseases, as well as help create objective methods of psychiatric diagnosis, identify biomarkers of mental illness, and improve pharmacotherapy. The aim of this work is to present the characteristics of DTI as well as current research on its use in schizophrenia, affective disorders, and other mental disorders. Despite their diversity in terms of psychopathological symptoms and causes (etiopathogenesis), many mental illnesses and disorders are characterized by certain common features in their clinical pictures. One of the most important and frequently studied etiopathogenetic factors are disorders of the brain’s structure and function. Knowledge about the relationships of structural and functional anomalies—in both gray matter and white matter—with psychopathological symptoms is still incomplete . The stuMagnetic resonance imaging (MRI) allows imaging of the brain with very high resolution. Moreover, MRI enables us to study not only the structure but also the function of the brain by measuring the flow of oxygenated blood with blood-oxygen-level-dependent (BOLD) imaging. Researchers in the field of neuroscience have begun a discussion on the currently used classifications and diagnostic criteria for mental illnesses, which are still based on subjective clinical assessment . NeuroimThere has been intense development in the field of imaging in recent decades. Neuroimaging is widely employed in psychiatry, as it can be used not only as a supplementary method for making a diagnosis, but also in the search for new drugs, to study the mechanisms that organize the mental life of the individual, and to identify the causes of neurobiological mental diseases. Neuroimaging can be helpful in assessing the effectiveness of treatment, as well. This is a complicated problem, for which various types of psychopathological scales are currently being employed. The use of imaging to measure therapeutic effects can increase the objectivity of this process . Unlike The number of available neuroimaging techniques has increased in recent decades. The use of functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) has enriched the arsenal of psychiatry . One of The aim of this work is to present the DTI neuroimaging method and discuss its use in psychiatry. It will be illustrated using schizophrenia, affective disorders, and other mental disorders as examples. The limitations of this method will also be presented.DTI uses magnetic resonance imaging to assess the diffusion properties of water in intra- and extra-cellular space. It does not require the use of additional equipment, contrasting substances, or chemical markers . DiffusiThe movement of water in tissue is determined by the type of tissue, its architecture, integrity, and the presence of barriers . Based oThanks to magnetic resonance imaging, it is possible to measure water diffusion in a single voxel  over a timespan of a few milliseconds, thereby recording the magnitude and direction of such diffusion. These data are then used to create a mathematical construct known as a “tensor”, which graphically represents diffusion within the voxel. Combining the data collected from the entire area being studied allows us to model the course of bundles and graphically represent the diffusion distribution. These data, in turn, allow us to conduct a tractography . This provides a very accurate model of a tissue , which, in the past, was only possible in post-mortem studies.DTI analysis uses several coefficients which are calculated for the corresponding diffusion tensor. The most frequently used are fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). The most common indicator of all is FA. This is a standardized measure with values between 0 and 1, and it roughly shows how much water within the micro- and macro-structure undergoes anisotropic diffusion. It is often interpreted as an indicator of white matter integrity , as it is associated with the level of axonal ordering within bundles, their myelination, and any disruptions they might have sustained . ReductiIt is difficult to use this method in everyday clinical practice due to its complexity. Conducting neuroimaging using DTI requires special data acquisition protocols, data developed to assess artifacts in the obtained data, and quality control, visualization, and subsequent mathematical analysis of the obtained data . DTI resSchizophrenia is a severe chronic neurodevelopmental disease. It hinders the functioning of a large proportion of patients to such an extent that their life in society is significantly disturbed. It affects every sphere of mental life: thought, emotions, and behavior. The prevalence of the disease in 2016 was estimated at 0.28%. Despite this relatively low prevalence, it is a common cause of disability, especially in middle-income countries. Furthermore, it is associated with shortened life expectancy and increased mortality is observed in all age groups. Schizophrenia also has increased comorbidity with other chronic diseases, such as heart disease, diabetes, some cancers, respiratory diseases, and strokes .Schizophrenia has been much studied by neuroscience. The etiopathogenesis of this disease is still not fully understood. In the nineteenth century, when it began to be diagnosed as a disease based on diagnostic criteria, there were many hypotheses about its causes. Eugen Bleuler saw the causes of this disease in the disintegration of the psyche . On the Thanks to development in various fields of science, it has become possible to test the disconnection hypothesis. It assumes that psychopathological symptoms are caused by incorrect communication between functional regions of the brain, rather than by the disorder of one specific area of the brain. Histopathological examinations seem to confirm this, as reduced numbers of neuroglia cells, disorders of the myelin sheath structure, mitochondrial degeneration, reduction of presynaptic follicles, and neuronal atrophy have been found in post-mortem studies of people suffering from schizophrenia .Many reports indicate the crucial role of the prefrontal cortex (PFC), the temporal cortex, and their connecting fibers in the etiology of schizophrenia. The PFC has broad connections with almost all cortical and subcortical areas, which gives it the unique position of controlling many cognitive functions. These functions include working memory, declarative memory, rule learning, planning, problem solving, recognition of new stimuli, attention control, motivation control, language control, inhibition of reactions, decision making, emotion control, and social cognition . The maiDespite many years of research, the results of white matter structure studies are still inconsistent in patients with schizophrenia. Table The corpus callosum is the white matter structure deep inside the cerebral fissure. It is the largest commissural fiber of the brain, expanding deep into both hemispheres, and it connects many distant areas of the brain with each other. It helps coordinate cognitive processes and behavior. It is believed that aberrations within this white matter structure play a significant role in the etiopathogenesis of schizophrenia . Many stThe cingulum is the most important white matter structure within the limbic system. It is under the cingulate gyrus and passes over the corpus callosum. It is responsible for the connection between the neocortical areas and the limbic system; it also connects the limbic system with the subcortical areas of gray matter. It plays an important role in controlling the expression of emotions, attention, motivation, and working memory. Disorders of these functions are often observed in schizophrenia . DecreasThe superior longitudinal fasciculus (SLF) is another important white matter structure. It is divided into four parts. They connect the area of the frontal lobe and the operculum with the upper part of the parietal lobe (SLF I) and the angular gyrus (SLF II), and the supramarginal gyrus (SLF III) with the superior temporal gyrus (SLF IV). The fourth part of the superior longitudinal fasciculus is also called the arcuate fasciculus. It connects Wernicke's area (Brodmann's area 22) and Broca's area (Brodmann’s areas 44 and 45). Its activity is associated with many key functions necessary in everyday life, such as speech, using tools, thinking ahead, and empathy. It is also involved in the control of spatial and visual function, motor skills, the process of hearing, and comprehending that which one hears and reads , 38. In The arcuate fasciculus belonging to the association fibers is a white matter structure which connects the lateral areas of the orbital–frontal cortex with the anterior part of the temporal lobe. It is involved in the performance of functions in the fields of memory, language, and controlling emotions. These processes are heavily disturbed in the course of schizophrenia. This may be caused by microstructure disorders of this nerve fiber. Changes in diffusion parameters in this area have been found in patients with schizophrenia. Decreases in FA are most frequently reported , 30, 36,The main association fiber connecting the temporal lobe with the occipital lobe is the inferior longitudinal fasciculus. It is believed to be involved in many important brain functions because of the areas which it connects. This structure is responsible for recognizing objects and other people, it is involved in the process of seeing, and it is important when reading and comprehending text. Furthermore, it is responsible for visual memory and participates in the control of emotional processes . AuditorTable Some reports discuss the influence of neuroleptics on the integrity of white matter. Research suggests that atypical neuroleptics may have a neuroprotective effect. Previously untreated patients experiencing their first episode of the disease who underwent 6 weeks of therapy with amisulpride were found to have normalized diffusion indexes. These results indicate that dopaminolytics may have a remyelinating effect  and may Deficit schizophrenia is a subtype of schizophrenia characterized by the presence of both primary symptoms and persistent negative symptoms, regardless of the stage of the disease and the treatment applied. It is quite a rare subtype of schizophrenia and its prevalence in the population of people suffering from schizophrenia is about 15% . It was In MRI studies, clear morphological markers of deficit schizophrenia have not yet been determined. In recent years, a number of studies using DTI have been conducted to assess the structure of white matter in patients with deficit syndrome. Changes in the values of diffusion indices have been described in the inferior longitudinal fasciculus on the right side , the rigSome research results suggest that the underlying cause of deficiency syndrome symptoms is impaired communication between different areas of the brain; however, there is still not enough evidence to allow certainty on the matter. Water diffusion disorders in white matter in the prefrontal cortex areas indicate that these areas play an important role here .DTI studies have also shed light on major depressive disorder (MDD) and bipolar disorder (BP).Depression is the most common mental illness and one of the most common causes of absences from work ; it is cThe etiopathogenesis of depression remains unknown. In recent years, there has been an increase of diffusion imaging studies examining affective disorders. The results are, however, inconclusive. Some theories suggest that MDD is rooted in disorders of the cortico-subcortical network . It has Research in this field thus far has noted various types of changes in diffusion parameters, which suggests disruption to the integrity of white matter pathways. The decrease in FA and increase in RD throughout the whole brain is consistent with disruption in the whole brain between cortical and subcortical areas . The lesIn 2019, the ENIGMA consortium published a major meta-analysis which included DTI of 1,305 people diagnosed with MDD. A decrease in the FA index was observed in 16 out of the 25 white matter tracts of interest. The largest changes compared to the control group were found in the corona radiata, corpus callosum, and external capsule. Lesions were also observed in the superior fronto-occipital fasciculus, internal capsule, and fornix. These changes were more pronounced in patients with recurrent episodes, those who first experienced MDD after the age of 21, and patients who were not taking antidepressant medication during the study . Other sMore than 50% of patients suffering from non-psychotic depressive disorder do not achieve remission during pharmacotherapy with one antidepressant. There is also no clinical tool that can reliably plan completely effective therapy. Differences in white matter diffusion values in some brain structures may be a biomarker of disease remission after treatment . A decreBipolar disorder is a chronic psychiatric disease with a variable course. The main psychopathological features of this disease are mania and depression, which occur with varying intensity and severity. The etiopathogenesis of this disease remains unknown .In recent years, intensive research has attempted to assess the role of white matter in bipolar disorder. DTI studies may suggest that BP is also a disease associated with connection disorders in certain areas of the brain. It may be associated with disorders of the connections of the frontal and limbic areas, but also of the parietal and temporal cortices . This isDecreased FA appears mostly in the corpus callosum, cingulum, corona radiata, internal capsule, superior longitudinal fasciculus, and fronto-occipital fasciculus , 61, 69.DTI can also help distinguish between disease subtypes. It turns out that, compared to type II BP, the arcuate fasciculus presents a definite decrease in FA in type I BP. This may be of key importance for diagnosis, planning pharmacotherapy, and assessment of prognosis .Suicide is a massive problem across the world—800,000 deaths a year are due to suicide, and there are 20 times this number of attempts . People In the last decade, there has been increasing interest in applying diffusion imaging to assess non-schizophrenic and non-affective mental disorders. This chapter will discuss white matter abnormalities in the most-studied anxiety and personality disorders.One anxiety disorder whose cause is often seen as biological is obsessive–compulsive disorder (OCD). It is characterized by the presence of intrusive thoughts and repetitive compulsions. Studies have found increased diffusion values—associated with decreased white matter integrity—in the dorsal anterior region of the cingulum of people suffering from OCD. Moreover, a decrease in FA in other structures also correlates with the severity of OCD symptomatology . OCD patExtremely traumatic experiences, such as accidents, warfare, or abuse, can lead to the anxiety disorder known as post-traumatic stress disorder (PTSD). It is a chronic disease affecting the daily functioning of the individual and its severity may be based on changes within the white matter of the brain . In adulRecent studies suggest that white matter integrity disorders may underlie some personality disorders. Borderline personality disorder is the most researched personality disorder. This may be related to the fact that it is the personality disorder associated with the largest number of hospitalizations. It is characterized by instability in various areas of mental life such as emotions and self-image, as well as difficulties with social relationships. It is most frequently related to disorders of connections between the areas of the prefrontal cortex and the limbic system, but also some association bundles connecting the prefrontal cortex with the temporal and occipital areas of gray matter. Decreases in FA may occur in the cingulum, corpus callosum , the left inferior longitudinal fasciculus, and the right superior longitudinal fasciculus . Other sAnother personality disorder that has been studied with DTI is antisocial personality disorder, which is characterized by a lack of empathy, impulsive behavior, and a tendency towards aggression and manipulation . A certaWe can formulate some basic conclusions based on the above literature analysis regarding the application of magnetic resonance diffusion imaging techniques to psychiatry. First, DTI is widely used in scientific research on psychiatry. The DTI technique is an imaging method that can assess diffusion in tissues and thereby image white matter structures. By assessing various diffusion parameters , it is possible to draw conclusions about the properties of white matter fibers. Second, the disconnection hypothesis is one attempt to explain the etiopathogenesis of schizophrenia. It seems that neural communication disorders most often occur between the prefrontal cortex and the cortex of the temporal lobe, limbic system, and occipital lobe. A number of reports discussed in this work also indicate changes in diffusion values in nerve fibers. These changes are often interpreted as diminished integrity in white matter.Some studies suggest that the occurrence of deficit syndrome is associated with impaired communication between areas of the brain; however, there are currently not enough observations to draw hard conclusions on the matter. Third, white matter connectivity aberrations may underlie affective disorders. Changes in connections between the frontal cortex and the limbic system  may be associated with the development of depression and bipolar disorder. White matter disorders are probably also important in the etiopathogenesis of anxiety and personality disorders. Unfortunately, there is insufficient research in this area.It seems necessary to conduct future research using this technique. Thanks to studies done on large populations, it can be said with certainty that there are changes in the structure of white matter associated with many diseases and mental disorders. Future research should focus on the relationship between detailed symptomatology and white matter. Accurate morphological assessment of individual bundles in these disorders will also be important. In future research, it will be very important to pay attention to exogenous factors that may affect the structure and functioning of bundles, such as pharmacotherapy, for example. The future use of neuroimaging in psychiatry depends on the ability to transfer results from research on large groups to the individual level of the patient, which will be significant for clinical practice, diagnosis, therapy, and prognosis .In the future, a good understanding of DTI, its capabilities, and its limitations may be necessary for the everyday practice of psychiatry. Someday, this method may be routinely applied during diagnosis, when planning pharmacotherapy, or for assessing a patient’s prognosis. A basic command of this field will also enable practitioners to better comprehend the processes underlying mental illnesses and disorders.


Published literature and scientific events provide opportunities to expand knowledge and develop skills in the care and use of non-human primates (NHPs) in research. Increasingly, these traditional routes of information exchange are being complemented by dedicated online resources aimed at sharing best practice in NHP care and use, and enhancing the training and professional development of laboratory staff working with NHPs. This article outlines some key online resources from the UK’s National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) and other organisations with an interest in NHP research, and the ways in which the resources can be integrated into staff training and research practices to enhance animal welfare, quality of science and application of the 3Rs. These developments, coupled with changes in academic publishing such as open-access journals and greater self-archiving of research outputs, and a movement for greater openness in animal research, have led to an increase in the amount of information available online about the use and care of non-human primates (NHPs) in the laboratory. This knowledge base provides an important opportunity for staff to improve the welfare of the animals in their care and the quality of science derived from them, as well as a means to enhance public support for NHP research. However, as with other forms of knowledge exchange, there is a need to consider the quality and timeliness of the information being shared.1 is committed to supporting the scientific community to implement the 3Rs . We have an extensive programme designed to support scientists, veterinarians and animal care staff who work with NHPs. As part of this programme, we have developed a series of freely accessible, high-quality online resources (The NC3Rsesources  to enhan22.1(Macaca mulatta) and cynomolgus macaque (Macaca fascicularis), their behaviour , captive management  and tools for welfare assessment . It features over 200 images and videos, along with practical guidance, which is peer reviewed and referenced. Developed by the NC3Rs (Mark Prescott), with assistance from Emily Bethell and Caralyn Kemp of Liverpool John Moores University, the aim of this highly visual resource is not to provide a manual on macaque care and use, but instead to inspire, inform and share good practice to improve the welfare of these animals in laboratories worldwide. Individuals from 25 organisations internationally contributed material for the website, including major academic and industry laboratories and research field sites.The Macaque Website, launched in May 2015, covers the life history of the rhesus macaque A good understanding of the behaviour of the species staff members work with is fundamental to fulfilling the refinement principle of the 3Rs. It underpins, for example, effective environmental enrichment strategies, empathetic human–animal interactions, and the ability to use behaviour to identify animals with compromised welfare before issues become serious. Many scientists, veterinarians and animal care persons working with macaques in research and testing do not have a formal training in animal behaviour, and initial mandatory training programmes may concentrate on occupational health and safety and conducting scientific procedures, at the expense of behavioural aspects. This can compromise the ability of research organisations to operate to best practice in their use and care of NHPs.The comprehensive behaviour section of the Macaque Website provides a guide to social and non-social behaviours likely to be performed by captive macaques. It enables laboratory staff to better recognise, interpret and respond appropriately to macaque communication signals, which will provide a good basis for refining many aspects of their care and use. The welfare assessment section of the site also features a 1 h “Listen Again” presentation on recording behaviour, which provides the essential training required for more formal assessment of animal behaviour, such as that required in a small research project to evaluate the effectiveness of a new enrichment device. The presentation is also useful to students of primatology and animal behaviour. An interactive quiz to test knowledge of macaque behaviour has recently been added to the site.Not everyone working with macaques in research has the opportunity to travel to other laboratories and to compare and contrast their infrastructure and practices with those of others – to see whether they are ahead or behind the curve with their animal management and to gather new ideas. The Macaque Website illustrates some exemplary accommodation and enrichment ideas instantly in photo and video format. In doing so, it helps to dispel some common myths – for example, that macaques used in experiments must be housed in small, squeeze-back cages, else they will be difficult to capture; that animals with head implants cannot be housed socially in enriched enclosures; and that destructible materials such as wood and cardboard are not safe as enrichment items. It demonstrates the high standards that can be achieved with sufficient awareness, will and resources and enables laboratories to benchmark their standards against those of other laboratories. To assist research establishments to implement what is shown on the site, there is practical advice – for example, recipes for cheap enrichment items, as well as ideas for incremental improvements in caging design where resources are limited. Such information is particularly useful for those working in NHP laboratories in developing countries.The field of animal welfare science is constantly evolving and new, improved methods for assessing welfare emerge. The website pulls together some of the tools that can be used to identify individuals at risk of poor welfare and to evaluate the impact of refinements in research and husbandry procedures – from body condition and alopecia scoring systems, to haemodynamic, respiratory and blood clinical chemistry reference values. The NC3Rs is a major funder of new methods for assessing pain and distress in macaques, as well as new research materials that enable scientific procedures to be performed with reduced harm caused to the animals. As these research projects deliver practical tools for welfare assessment, they will be added to the website so that the latest techniques can be employed by others.2.2, called Common Marmoset Care. This site was developed by Claire Watson and Hannah Buchanan-Smith at the University of Stirling, with funding and input from the NC3Rs (Mark Prescott) and Primate Society of Great Britain. Launched in October 2011, the interactive site provides a wealth of information on how best to care for these small New World monkeys in captivity. The key audiences are researchers, private owners, educators, and zoo and laboratory professionals. There is a strong presumption on the website against the keeping of these animals as pets.The Macaque Website is complemented by an earlier website on the behaviour and care of common marmosets Like the Macaque Website, Common Marmoset Care is highly visual, with over 100 images and videos. The site includes a comprehensive section on understanding marmoset behaviour, with information to help users of the website to interpret the actions, facial expressions, body postures and vocalisations of these animals, as well as an interactive quiz to test acquisition of knowledge. The section “In the Wild” contains a gallery of images of common marmosets in their natural habitat, and a 5 min video illustrating a day in the life of wild marmosets in Brazil.There is also extensive information on aspects of marmoset husbandry and use in research, such as housing, grouping, feeding, handling and interactions with humans. One of the most valuable and unique features of the website is the large collection of videos demonstrating practical environmental enrichment strategies for these animals – from objects to encourage play and natural foraging behaviour, to ways to stimulate the senses and encourage exploration.As with the Macaque Website, the marmoset site can be used to gather enrichment ideas, benchmark housing standards, assess NHP welfare using behavioural indicators and contribute to staff training. Whilst not as well referenced as the Macaque Website, there is a list of links to useful publications. Additional video material on the handling of common marmosets and their use in Parkinson’s disease research is under development.2.3The Chronic Implants Wiki (CIwiki) represents a novel approach to sharing of information within the NHP neuroscience community. The focus is on refinement of the implanted devices used to enable electrophysiological recordings from the brain in long-term neuroscience studies, such as head posts and recording chambers. The NC3Rs has played an important role in encouraging innovation in this area, through workshops, research funding and prizes. Like the well-known Wikipedia, the CIwiki relies upon contributions from registered users, who can continuously edit the pages within the wiki, but unlike Wikipedia, its pages are visible only to authenticated individuals. To register to use the wiki, complete the short registration form on the home page and email it to the moderator.Recent years have seen considerable innovation in implant design, utilising advances in medical technology and engineering to produce devices which are more tissue friendly, integrating better with the skull, with reduced risk of infection at the implant margin. Such designs benefit not only animal welfare but also science, since infection and inflammation can lead to breakage or loosening of the device and animals having to be temporarily or permanently removed from the study. Whilst improvements in methodology are sometimes reported in the peer-reviewed literature, this is not always the case, perhaps because they carry less prestige than those reporting new scientific discoveries. The wiki was the idea of Daniel Adams, University of California, San Francisco, and is managed by the NC3Rs (Mark Prescott). It provides a secure forum for sharing of refinements to established techniques, no matter how incremental, rapidly and easily, with the prospect of feedback. Information on technical complications and flawed approaches is also useful to de-risk future ventures and avoid repetitions of failures.The wiki was launched in December 2015 and currently contains practical information  on issues such as implant design, construction materials, surface coatings, holding mechanisms and infection control, as well as information on some non-invasive approaches for head immobilisation. The content and utility of the wiki will expand as there is increasing active engagement from the international neuroscience community.2.4A hub of the main NC3Rs website includes additional information on opportunities to reduce harms and improve the welfare of NHPs used in research, as identified by various scientific working groups of the NC3Rs. For example, there are recommendations to refine the use of food and fluid control as motivation tools for macaques used in behavioural neuroscience, to incorporate positive reinforcement training techniques into husbandry and scientific procedures in order to reduce distress, to wean macaques at an appropriate age for behavioural competence, and to safely rehome exlaboratory primates where this is in the best interests of the individuals involved. Links are provided to the open-access, peer-reviewed journal articles, which contain the background information and evidence bases to support the recommendations for refinement. Also in this area are details of the annual NC3Rs event dedicated to promoting ways to improve primate welfare (Primate Welfare Meeting), and the NC3Rs guidelines “Primate accommodation, care and use”, which set out principles of good practice in the care and use of NHPs. Implementation of the principles in the guidelines is a condition of receiving funds from any of the major UK public funding bodies of NHP research.2.5The NC3Rs  has also led a number of projects to challenge the need for NHP studies in drug discovery and development, and to optimise study designs where their use is necessary for the testing of new pharmaceuticals and biologics. This has involved pre-competitive data sharing between more than 30 industry companies, contract research organisations and regulators, especially in Europe and the USA. In some cases, the evidence base generated has led to regulatory change in addition to changes in policy and practice within the participating organisations. The peer-reviewed output from these projects is conveniently collated in a hub of the main NC3Rs website. These include new opportunities for reducing the use of NHPs in the development of biotherapeutics, as recovery animals on toxicity studies, for the study of drug abuse potential, and for the prediction of pharmacokinetics for compounds cleared by hepatic cytochrome P450 enzymes. There is also published information on reducing the upper limit for body weight loss in maximum tolerated dose studies, and allowing social housing during telemetry recordings in safety pharmacology and toxicology studies.2.6mark.prescott@nc3rs.org.uk .The UK Animals (Scientific Procedures) Act 1986, amended 2012, requires that establishments breeding and/or using animals in scientific procedures appoint a Named Animal Care and Welfare Officer (NACWO), who has responsibility for the day-to-day care of the animals . In 2013, the NC3Rs established a network for NACWOs working with NHPs to enable sharing advice, experience and ideas, via an annual meeting, exchange visits and a dedicated email discussion group. Recently a decision was made to expand the network to include people working in similar roles outside of the UK. Animal welfare officers working with NHPs can join the email discussion group by contacting 2.7www.nc3rs.org.uk/ARRIVE), which were developed to improve the reporting of in vivo studies, in order to maximise the information published and minimise unnecessary studies. To date, the ARRIVE guidelines have been endorsed by more than 1000 journals internationally and many research funders and learned societies.Another NC3Rs resource worthy of note is the Experimental Design Assistant (EDA). Unfortunately, evidence exists to show that many animal studies, including those utilising NHPs, are poorly designed, analysed and reported and that this has significant implications in terms of reproducibility and the translation of findings into clinical benefits . The EDALaunched in 2016, the EDA is an online web application, with an associated website which contains a wealth of information and advice on experimental design. It was developed by the NC3Rs  in collaboration with in vivo scientists and statisticians from academia and industry, along with software developers specialising in artificial intelligence. Having created a user account, researchers from a wide variety of disciplines can use the application to build a visual representation of their intended experiment (the EDA diagram), based on a pre-established ontology. The EDA diagram is a more comprehensive and transparent means of summarising an experiment than a conventional text description. A “critique” function enables users to receive feedback and advice on their diagram (based on an extensive dataset of rules), in order to optimise their experimental design and analysis. The feedback may include, for example, highlighting the implications of some of the design choices made, or pointing out issues with internal consistency such as where two variables are confounded. Built into the system is dedicated support for randomisation, blinding and sample size calculation. The final, improved and transparent experimental plan can then be shared directly with colleagues  from within the EDA.3International Guidelines for the Acquisition, Care and Breeding on NonHuman Primates .Primatological and primate veterinary societies also have a presence online see . In addiPrimates , which hhttps://www.primatevets.org/education).The Association of Primate Veterinarians produces education resources for its members, some of which are free to download – for instance, a series of guidelines on topics relating to the use of NHPs in biomedical research from its Scientific Advisory Committee, and a “NHP Formulary” of drug doses and normal physiological values for commonly used species . However, much information relevant to the care and management of NHP species used in biomedical research, and on applying the 3Rs to this use, is published in general biology, laboratory animal science and animal welfare journals, as well as discipline-specific journals, such as those within neuroscience, immunology and infectious disease, psychology and toxicology. Therefore, it is important to conduct a well-conceived literature search of mainstream bibliographic databases and academic search engines, such as PubMed and Scopus, before embarking on new research projects and reviews of facility practices so that all of the latest relevant information can be taken into account. Guidance on searching for alternatives  is provided by Altweb  and the Animal Welfare Information Centre .Many primatological societies publish their own journals, which are a rich source of information on NHP behaviour and care in captivity. Some key journals are listed in https://www.researchgate.net/). It is also worth searching academic search engines too, as there are many good books available for free online, such as The Psychological Wellbeing of Nonhuman Primates (Increasingly, research papers are freely available in online repositories, as scientists publish their work in open-access journals in order to comply with the mandates of funding bodies and to give the work greater visibility and impact. Where papers are not available as open access or via an institutional subscription, they can sometimes be obtained from the author’s ResearchGate profile (Primates .Some regulatory and funding agencies have created online resources on aspects of NHP care and use – mainly bibliographic databases – either directly or supported via grant funding. Key resources are listed in 4Research with NHPs is a complex undertaking requiring a team approach from people with varied and specialist knowledge and skills. Conducting the very best science depends on keeping abreast of the latest knowledge and techniques, not just in research methods and scientific procedures, but also in NHP behaviour, management and welfare, as increasingly studies demonstrate a link between good animal welfare and quality of science . ResearcTo maximise use of these resources and the information they provide, they should be integrated into local research and animal care practices. This can be done by, for example, incorporating them into the content and delivery of staff and student training courses, linking to them from relevant areas of the organisation’s intranet, raising awareness with e-newsletters and/or posters, and using the material to review and revise standard operating procedures. Ultimately, this will help to raise standards of NHP care and use, facilitate research collaborations, and address societal concerns about NHP research.


This paper describes how autonomy emerged in a team in a large public organization and which factors were important in this process. The organization has back sourced software development and abandoned a stage-based software development process with many handovers between business, IT and vendors. We collected data in four semi-structured interviews and analyzed information on changes in the structure and responsibilities of the team. The team has refined its portfolio for better cohesion, stepwise taken over the responsibility for software development from the vendor and in parallel recruited software developers, UX designers and testers. Product owners have joined the team as well. Supported by changes to the financing model, the team has transformed from mediating between business and vendors to a cross-functional product team with autonomy over its budget, backlog and software development process. As a result, the team can better balance between delivering new features and quality improvements, continuously deliver software with less overhead and focus on its mission to deliver user-friendly services with increased involvement of domain experts. Defining a clear product boundary and reducing dependencies on other teams, developing necessary skills and changing the financing model are recognized as the main success factors, as well as the main challenges in the transition process. Agile software development has become the norm in the industry and is increasingly getting a foothold in the public sector, albeit so far not as an exclusive approach . Public In this paper, we present a single case study of a team in the Norwegian Labour and Welfare Administration (NAV) that adopted agile methods while taking ownership of previously outsourced IT systems. We describe how the team evolved from supporting product owners for the acquisition of systems from an external vendor to an autonomous agile team with full ownership of the applications it is responsible for.A systematic literature review on agile methods in the public sector citing 17 primary studies reported several benefits, including faster value delivery, increased end-user satisfaction, lower cost, better collaboration between business and IT, reduced dependency on contractors, and improved team morale. Factors making adoption difficult included an unsuitable organizational culture, lack of experience with agile methods, the ingrained use of prescriptive approaches, and big bang deliveries. In addition, the public sector often runs “IT megaprojects” and relies heavily on traditional procurement and contracts, which make agile adoption challenging .backsourcing (or insourcing), i.e. bringing the outsourced components back in-house [The 1990s and early 2000s saw a wave of outsourcing when organizations, often in the pursuit of cost savings, outsourced IT, oftentimes to low-cost countries. Lack of client involvement and competence is reported as a major challenge. A more recent trend, spurred by factors such as the recognition of IT as a core competence, unmet goals with outsourcing, and the need for better control of the IT systems, is in-house .There is an extensive amount of literature on autonomous teams and different types of autonomy such as autonomy over product, people and planning decisions . AutonomNAV was founded in 2006 by merging three large organizations in the public sector. NAV has 19000 employees including an IT department of over 700 employees and administers a third of the Norwegian national budget through various benefit schemes such as pension, unemployment and child-care benefits. The end-users of IT applications are twofold: organizations and individuals in Norway on the one hand, and the employees of NAV who manage the benefits on the other. Since the establishment of NAV, IT development and maintenance has mainly been outsourced to several vendors, with NAV responsible for requirements specification, acceptance testing and operation of services. In 2017, due, e.g., to high development costs and the growing need for digitalization of services, NAV decided to backsource most of the IT development. In addition, the organization has gradually adopted agile development to achieve better commitment, motivation to perform and desire for responsibility in the organization.In previous work , we descThe team in this case study develops and maintains the information and user interfaces intended for the general population provided via the organization’s main website nav.no, apps and in other channels. The team is also responsible for developing organization-wide guidelines for publishing information online.The research presented here is a single qualitative case study and part of a larger study into agile adoption and backsourcing in NAV. We selected the case due to the insights it provides on enabling team autonomy in a complex setting. We collected data through four semi-structured interviews , which fIn this section, we present the results, first discussing the transition of the team, followed by discussing factors that enabled the transition towards an agile autonomous team.Before backsourcing, over 50 applications covering a broad range of user interfaces were managed by a group of employees organized in an office in the IT department. The office managed the contract with the vendor, provided support to the business side, and followed testing, deployment, and operations of the applications. The employees of the office had roles such as functional experts, technical experts, team leaders and project leaders. Functional experts had deep domain knowledge, while technical experts focused on non-functional aspects and technology. The business side, organized in other departments in NAV, specified the requirements, prioritized the backlog, financed changes (often via projects), evaluated the estimations and design, and tested the final applications. The vendors estimated the costs of changes and designed and developed the solutions. The process thus required many handovers between business, IT and vendors. Changes were often delivered in a few large deliveries per year to manage dependencies between services.In the first step in the backsourcing process, the portfolio covered by the office was divided and assigned to multiple teams. In this process, the team “Self-services” was established, consisting of a team leader, six functional experts and one technical expert. The vendor had its own team collocated at NAV, with seven developers and one team leader. Figure Building internal development capability. Before backsourcing, the team consisted of functional and technical experts while the developers were on the vendor side. The business department owning the applications financed recruiting 3 developers in 2018, the first one starting in February. This was considered a major step towards insourcing software development.Competence transfer. The team had little knowledge of the code prior to the backsourcing. The IT-team and the vendor team started working together on software development for the purpose of competence transfer; including working shoulder to shoulder and pair-programming.Analyzing the applications and planning the handover. The outsourcing contracts included steps for handover to other vendors but not to NAV. The team and the vendor performed an analysis of applications regarding their status  and developed a roadmap with milestones and actions for a stepwise handover of applications.Defining the product boundary in steps. The old contract model put many applications to be developed by a single vendor in the same contract. As a result, the contract included over 50 applications, all related to user interfaces but managed by different stakeholders. By September 2017, the portfolio of applications was divided between two teams with a shared team leader: “Team A” (services for unemployment) and “Team B” followed here, named “Team Insight”. Some applications were handed over to other teams as well. The purpose was to separate concerns and avoid communication with multiple product owners.Transfer of ownership and responsibility; becoming self-sufficient competence-wise. By June 2018, the team had the full responsibility for software development. A User experience (UX) designer was recruited in addition to getting support from two external UX designers. A new tester, who used to be a functional expert, was added to the team as well. Thus, the team included all necessary skills for software development. The team changed its name to “Personal users” to highlight its focus. Some functionality was left out to be handled by “Team C”.Becoming an autonomous product team. By January 2019, the team was fully financed by the business side and one functional expert became a product owner, enhancing his competence by taking courses and participating in product owners’ fora. This type of team is called a “cross-functional product team” (in short Product Team) and the team owns its budget, product backlog and its prioritization.Enhancing the portfolio. In January 2020, the team merged with an IT team responsible for the information on web pages, which had backsourced its applications as well  the product factor: i.e. defining suitable product teams with fewer dependencies on other teams and a more coherent portfolio. In this process, it has been challenging to handover legacy applications to other teams with limited budget and capacity; and 3) the financing model is still not homogenous and creates challenges in prioritization and planning.The reported challenges were mainly related to 1) the In this paper, we understood team autonomy in agile software development as having the power to plan and prioritize the work of the team according to budget, resources, roadmaps and constraints, and to have ownership of the processes and practices employed. This required several changes in the organizational structure and processes, and even the financing model. The autonomy to plan and prioritize work was implemented through incorporating the product ownership in the team. In this case, the organization was able to design the work of the team to have a rather independent portfolio, making it possible to have a high degree of autonomy. Our findings about how to enable team autonomy are well in line with what other cases have reported, as summarized in . In partOur finding regarding the need for changing the financing model points to the importance and challenges of portfolio management in large-scale agile development, an area which currently has a lack of research. Furthermore, our findings indicate that outsourcing relationships can lead to a high degree of technical debt if there are lack of financing to remove technical debt and lack of mechanisms to incentivize high code quality.The findings in this paper are based on four interviews with practitioners in the studied team in different roles, as well as of an analysis of other documents such as presentations. While this limits the generalizability of the findings, they are well in line with existing literature, and point toward a need for deeper understanding not only of how autonomous teams can work, but of the surrounding organizational context. Two of the authors are employees of NAV, which could introduce bias. However, the first author works in an independent role, and the findings are based on an analysis done jointly by the first two author.We presented a case study of how team autonomy was enabled in a single team in a large public organization. We discussed that many factors are required to enable autonomy, both in the team and in the organization. The team members agreed on the benefits of the transformation that happened over the course of three years and experience increased employee satisfaction, faster response to changes and more strategic thinking.By now, we have interviewed 35 employees in different roles and from different teams in NAV, as well as representatives from vendors. This paper is based on an initial analysis of the data from one team. We are extending our analysis to multiple teams with focus on backsourcing of software development and large-scale agile development.We thank NAV and the interviewees for the possibility to perform the research and for sharing valuable data and insights with us.


Nature-based solutions (NBS) have been defined by the European Commission as actions aiming to provide environmental, social, and economic benefits through the inclusion of natural features in the urban environment. The exposure to natural environments, including NBS in urban contexts, has been associated with a large number of health benefits  in individuals with adverse childhood experiences. In this perspective, the authors suggested that NE can positively impact the physiological and psychological health of children who have experienced trauma, opening the door to the potential beneficial effects of nature inducing a retroactive effect.Putra et al. presented a systematic review on 15 available studies highlighting mixed findings and methodological heterogeneity. In particular, green space indicators and pro-social behavior measures varied among studies and a lack of mediators and potential confounding variables was detected. This review provides preliminary evidence on the association between green space and pro-social behavior. Nevertheless, the authors underlined the need to further develop rigorous studies in order to identify underlying pathways in this promising association and suggested considering the role of perceived quality of green space as an important variable in relation to pro-social behavior.Inconsistent evidence has been found on the association between green space and pro-social behavior in children and adolescents. Sachs et al. showed that NE during childhood appeared to be positively associated with NE during college. Similarly, a pro-environmental attitude was positively associated with NE both in childhood and during college. This work enhanced the long-term effect of green space exposure during childhood also in light of the considerable decrease of time spent in nature during college. However, their study did not reveal any association between NE and stress levels, probably because, as reported by some participants, contact with nature could have been perceived as a waste of time given the many school commitments.Another neglected topic was found to be the relationship between NE and pro-social behavior among undergraduate students, a sub-population that is well-known for being at high risk of stress, anxiety and depression. Panno et al. in a sample of urban park visitors. The authors tested a novel modeling framework in which pro-environmental behavior was directly predicted by an emotion-regulating strategy  and indirectly through the experience of “being away” when embedded in a natural environment. This study offered relevant insights on the role of cognition and perceived restorative experience of the natural environment, which together prove to significantly trigger pro-environmental choices.Pro-environmental behavior was also investigated in a study by Browning et al. compared the impacts of simulated  and actual nature experiences on mood based on data from six published studies. Simulated experiences varied from looking at pictures to walking on the treadmill while watching a video of the natural environment. Results suggest a greater positive effect on mood due to the real experience of green exposure. This work also highlighted the possibility of considering valid alternatives, especially when green exposure is not possible, as in the case of recent confinement due to the COVID-19 pandemic.Although its multiple benefits are well-known, direct contact with the natural environment is not always possible. For this reason, Trammell and Aguilar. They found that natural environments could positively affect performance improvement when the required task involves a moderate attention level, while no effect was found on tasks requiring minimal or greater amounts of attention. However, this positive effect was greater in the indoor environment than in the natural environment. Physical activity, on the other hand, seemed to have beneficial effects on affect and cognition regardless of whether it was carried out in indoor or natural environments. This study suggests that a complex relationship exists between the natural environment and the benefits that cannot be reduced to the concepts of exposure and restorativeness. Other mechanisms may play a role in diversifying outcomes, including adaptation mechanisms.Surprising findings emerged in the study results by Ebisch. This perspective paper provides an overview of the unexplored role of the self and brain network interactions in the connection between green space and psychosis. This topic is of particular relevance, since psychotic disorders  have been a priority for the public health agenda due to the pervasiveness and chronicity of the disorder, high rate of hospitalizations and comorbidities, and premature mortality.With regard to complexity, new theoretical insights on green space exposure and the reduction of psychosis risk have been advanced by This Research Topic provides a multidisciplinary perspective of the human–nature interaction throughout the life-course in association with mental health and well-being. The studies included in this topic have generally demonstrated potential beneficial associations; however, they have also highlighted inconsistencies in the evidence available in terms of their applied methodologies and reported findings.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Over millions of years, Nature has optimized the motion of biological systems at the micro and nanoscales. Motor proteins to motile single cells have managed to overcome Brownian motion and solve several challenges that arise at low Reynolds numbers. In this review, we will briefly describe naturally motile systems and their strategies to move, starting with a general introduction that surveys a broad range of developments, followed by an overview about the physical laws and parameters that govern and limit motion at the microscale. We characterize some of the classes of biological microswimmers that have arisen in the course of evolution, as well as the hybrid structures that have been constructed based on these, ranging from Montemagno's ATPase motor to the SpermBot. Thereafter, we maintain our focus on bacteria and their biohybrids. We introduce the inherent properties of bacteria as a natural microswimmer and explain the different principles bacteria use for their motion. We then elucidate different strategies that have been employed for the coupling of a variety of artificial microobjects to the bacterial surface, and evaluate the different effects the coupled objects have on the motion of the “biohybrid.” Concluding, we give a short overview and a realistic evaluation of proposed applications in the field. Artificial micro- and nano-swimmers are small scale devices that convert energy into movement ; l is a characteristic length scale ; and η is the viscosity of the fluid. Taking the suspending fluid to be water, and using experimentally observed values for V, one can determine that inertia is important for macroscopic swimmers like fish (Re = 100), while viscosity dominates the motion of microscale swimmers like bacteria (Re = 10−4).Here, ρ represents the density of the fluid; The overwhelming importance of viscosity for swimming at the micrometer scale has some profound implications for swimming strategy, as discussed most memorably by Purcell. He invited the reader into the world of microorganisms and theoretically studied the conditions of their motion Purcell, .In the first place, propulsion strategies of large scale swimmers often involve imparting momentum to the surrounding fluid in periodic, discrete events , and coasting between these events through inertia. This cannot be effective for microscale swimmers like bacteria: due to the large viscous damping, the inertial coasting time of a micron-sized object is on the order of 1 μs. Using the typical speed of a microorganism, one obtains that the coasting distance is 0.1 Å. Purcell concluded that only forces that are exerted in the present moment on a microscale body contribute to its propulsion, so a constant energy conversion method is essential. Microorganisms have optimized their metabolism for continuous energy production, while purely artificial microswimmers must obtain energy from the environment, since their on-board-storage-capacity is very limited. As a further consequence of the continuous dissipation of energy, biological and artificial microswimmers do not obey the laws of equilibrium statistical physics, and need to be described by non-equilibrium dynamics. Mathematically, Purcell explored the implications of low Reynolds number by taking the Navier Stokes equation and eliminating the inertial terms:rate of motion is practically irrelevant for the motion of the microswimmer and of the surrounding fluid: changing the rate of motion will change the scale of the velocities of the fluid and of the microswimmer, but it will not change the pattern of fluid flow. Secondly, reversing the direction of mechanical motion will simply reverse all velocities in the system. These properties of the Stokes equation severely restrict the range of feasible swimming strategies. As a concrete illustration, consider a “scallop” that consists of two rigid pieces connected by a hinge. Can the scallop swim by periodically opening and closing the hinge? No: regardless of how the cycle of opening and closing depends on time, the scallop will always return to its starting point at the end of the cycle. Here originated the famous quote: “Fast or slow, it exactly retraces its trajectory and is back where it started.” In light of this “scallop theorem,” Purcell developed approaches concerning how artificial motion at the micro scale can be generated. This paper inspires scientific discussions until today; for example, a recent work of the Fischer group experimentally confirmed that the scallop principle is only valid for Newtonian fluids  can swim through periodic mechanical motions or deformations . First, the Nature has developed motile systems over time and length scales spanning several orders of magnitude, which have evolved anatomically and physiologically to attain optimal strategies for self-propulsion and overcome the implications of high viscosity forces and Brownian motion, as shown in Figure Some of the smallest known motile systems are motor proteins, i.e., proteins and protein complexes present in cells that carry out a variety of physiological functions by transducing chemical energy into mechanical energy. These motor proteins are classified as myosins, kinesins, or dyneins. Myosin motors are responsible for muscle contractions and the transport of cargo using actin filaments as tracks. Dyneins and kinesin motors, on the other hand, use microtubules to transport vesicles across the cell Vogel, . The mecBacteria: move due to rotation of hair-like filaments (flagella) anchored to a protein motor complex on the bacteria cell wall. More detailed information about bacteria will be discussed in section Bacterial Biohybrid Microswimmers, as the main focus of this review Berg, .Spermatozoa: if the male reproductive cell is (uni) flagellated and motile, it is referred to as a spermatozoon, a phenotype which is dominant in animals. Many uniflagellar spermatozoa are propelled by a snake-like wiggling of their flagella. This flagellar beat is a wave that propagates from the head of the spermatozoon to the tip of the flagellum : contain many hair-like extrusions all over the body (cilia). The ciliar beat has two distinct phases: the Motile algae: belonging to the filo Euglenophyta, these flagellated cells swim in a coordinated fashion, synchronizing one or several flagellar structures to achieve self-propulsion. Since most of these organisms undergo photosynthesis, many of them have eye-spots near the anterior pole to enable the algae colony to swim toward light  in a customized way. The carrier is the component responsible for the movement of the biohybrid, transporting the desired cargo, which is linked to its surface. The great majority of these systems rely on biological motile propulsion for the transportation of synthetic cargo for targeted drug delivery  and muscle cells  cells or myocytes, due to their capability of spontaneous contraction with no external driving stimulus. The power generated from the contractions is proportional to the cross-sectional area of the muscle cell-tissue assembly. Moreover, the contraction state can be prolonged when suitable light or electric pulses are applied, leading to increased tuneability , cylindrical shape, called rod and spiral cell shape (spirilla), amongst others  and different morphologies: spherical or ovoid cell shape, called s Young, . Bacteris Young, . Many siBacterial biohybrid microswimmers, composed of at least one living bacteria and one inanimate object, are the focus of a vibrant and quickly growing research field. So far, prototypes for a number of very different options have been implemented: the motile force can come from a single or many bacteria  of the cytoplasmic membrane, a thin layer of peptidoglycan, and an additional outer membrane, also called the lipopolysaccharide layer. Other bacterial cell surface structures include capsules and slime layers, which are secreted slimy or sticky materials made up of polysaccharides or proteins that cover the cells and are in direct contact with the environment; they have different functions, including attachment to solid surfaces. Additionally, protein appendages can be present on the surface: fimbriae and pili can have different lengths and diameters and their functions include adhesion and twitching motility  and hydroxyl ions (OH−) cannot diffuse across this membrane, allowing a charge separation that enables the proton motive force which is used to generate energy for different cell functions, including motility  and fluid phospholipid bilayer, which also contains numerous membrane-embedded and membrane-associated proteins. The membrane surrounds the cell separating the cytoplasm from the cell's environment and it is a selective permeability barrier for substances that enter and exit the cell . The cell wall may contain polysaccharides and proteins anchored through different mechanisms, and teichoic acids (TAs), covalently attached to peptidoglycan  or anchored to membrane lipids , threading through the peptidoglycan layers. TAs are long anionic polymers of repeating units of glycerol phosphate, glucosyl phosphate, or ribitol phosphate, and they are partially responsible for the overall negative surface charge of the Gram-positive cell envelope  and there is an outer membrane anchored to the peptidoglycan through lipoproteins Braun, . The innSwarming and swimming movements are both powered by rotating flagella  is a helical, thin and long appendage attached to the cell surface by one of its ends, performing a rotational motion to push or pull the cell  to perform mechanical work   for the bacterium to move in a directed manner along gradients and reach more favorable conditions for life  Berg, .V. alginolyticus carrying a 3 μm microbead  exhibited a clear indication of directional movement in the presence of L-aspartate as a chemoattractant , aerotaxis (oxygen), pH-taxis, phototaxis, thermotaxis, and magnetotaxis. Bacterial taxis has been exploited for the directed movement of bacterial microswimmers. For example, a concentration gradient of L-serine was created with a micropipette and used as an attractant for E. coli: with its peritrichous flagellation, E. coli performs a run-and-tumble swimming pattern  pattern  and by deletion of the chemosensory system (leading to smooth swimming cells that do not tumble). The increase of bacterial density inside the channel led to the formation of progressively larger rafts. Cells colliding with the raft contributed to increase its size, while cells moving at a velocity different from the mean velocity within the raft separated from it  . PLL was used to coat poly (ethylene glycol) (PEG) microbeads. Due to the submerging property of PEG beads on agarose gel, selective  coating with PLL was achieved. Characterization with Confocal Laser Scanning Microscopy using fluorescein labeled PLL revealed the patterned adhesion of bacteria on PEG microbeads, corresponding to the extent of coating with PLL    microbeads  and hydrophilic (patterned) PS surfaces. As an intrinsic property of S. marcescens, the production of a sticky pink slime leads to relatively unselective adhesion to surfaces, which is the reason why a large number of biohybrid swimmers use this specific bacterium. As will be discussed later, adhesion can be suppressed by covering the surface of the artificial objects with surfactants.Behkam and Sitti were the first to report the attachment of several E. coli on the metal  capped face of particles with a PS or silica core. The favored attachment to the metal part was found to be related to its hydrophobicity. Attachment assays and contact angle and zeta potential characterization showed that E. coli prefer Pt surfaces over the other three metals investigated. The metal-free side of the particle can be further functionalized with a desirable surface chemistry , showing the feasibility of the biohybrid for localized drug attachment  and magnetite (Fe3O4) nanoparticles. The resulting BacteriaBot exhibited directional motion in response to chemoattractant gradients and magnetic fields.Recently, Park et al. reported the preferential attachment of bacteria to stiffer elastic surfaces in comparison with softer surfaces, which could make the viscoelastic properties of the bacterial–surface interaction the most critical factor for bacterial attachment and the motility of biohybrid microswimmers , labeled with Cyanine (Cy5.5)-coated polystyrene microbeads, taking advantage of the high-affinity interaction between biotin and streptavidin.One of the most commonly used chemical strategies for the preparation of BacteriaBots harnesses the high affinity interaction between biotin and streptavidin. Streptavidin is composed of four identical subunits; each subunit can bind a single biotin molecule . The used antibody was raised against the O-antigens present on the cell membrane. This limits the attachment of the biotin-conjugated antibody (and thus streptavidin coated nanoparticles) mainly to the surface of the bacteria   and high bond dissociation (305–440 kJ mol−1), in comparison with bioconjugation approaches based on van der Waals forces, electrostatic interaction, hydrogen bonds and hydrophobic effects  with differently shaped objects is not sufficiently understood. It is well documented that particle size influences most aspects of interactions with living entities, including their degradability, attachment, uptake mechanisms, properties in flows, and excretion mechanisms. However, the lack of simple and reproducible fabrication methods for differently shaped nano- or microparticles makes studies relatively difficult. While some of the most extensive studies of interactions between eukaryotic cells and inorganic particles  . These are attached to the structures and move the surrounding fluid, resulting in effective propulsion. In the second case, the movement of a microobject is caused by bacterial turbulence, with no concrete binding of the bacteria to the surface of the structure.A very different shape that also aims for bacterial trapping was fabricated by the group of DiLeonardo (Vizsnyiczai et al., S. marcescens formed good bacterial carpets, while E. coli failed to bind completely, and S. typhimurium was little better. Even though the influence of shape was not discussed in depth, the authors characterized the position of the flagella above the carpets. In addition, the flows created by the bacteria—which were responsible for motion of the objects—were characterized by adding tracer particles. In another work, Kim & Kim relied on the slime produced by S. marcescens, which adheres naturally to surfaces, to create a bacterial carpet on SU8 squares (Kim et al., Firstly, we want to briefly examine the direct attachment of so called “bacterial carpets” to microstructures. In an early work, Darnton et al. created active bacterial carpets to move micro-objects with the shape of beads, microcars, and wedges (Darnton et al., The second strategy to move micro-objects does not rely on strict binding of the bacteria to the object surface, but rather achieves effective propulsion by bacterial turbulence, causing significant differences not only in the steadiness of the motion, but also in theoretical aspects and in versatility of the approach. Here, the most well-known examples include experiments on gear shaped micro-objects (Sokolov et al., In summary, it can be said that the influence of shape on the features of a bacterial biohybrid microswimmer is very poorly analyzed and understood, and more systematic evaluation, categorized after bacterial type, swimming strategy, and binding modality, are needed to deduce clear effects of the object shape.in situ production or selective release of therapeutic agents using bacterial biohybrid microswimmers would lead to reductions in the cost of therapy and the need for purification of drugs produced ex situ, as well as to a significant decrease of the dose of medicament supplied (Hosseinidoust et al., There are different potential applications of bacterial biohybrid microswimmers that exploit their capability to transport cargoes or reach targets in a customized way. For instance, these hybrid bioswimmers have been tested as drug delivery systems (Wang and Pumera, E. coli were exploited to sort and separate similarly-sized nanoparticles of dissimilar surface properties (Suh et al., P. mirabilis swimming bacteria were used to push non-motile Candida albicans fungal cells (Trivedi et al., E. coli biofilm. The biofilm could be attacked with antibiotics and was therefore more susceptible to chemical threat, even though the biofilm was resistant to conventional treatment (Stanton et al., in situ encapsulation of the protein into the cargo structure no longer seems so much like science fiction. However, the potential of bacterial hybrid swimmers is not limited to biomedical applications; the inherent sensitivity of bacteria to environmental stimuli could be well exploited to create motile sensors. This could build on the signal transduction systems inherent to bacteria, which allow the creation of whole-cell biosensors used, for example, in antibiotic discovery (Wolf and Mascher, Furthermore, the individual and combined power of bacterial movement can be exploited by the creation of hybrid micromachines for the development of mechanical tasks and applications. For example, the chemotactic properties of in vitro. Ideally, after cell division, daughter cells should bind immediately and automatically to available cargos in order to avoid “dilution” of the BacteriaBots. Finally, the detachment, and release of the cargo still has to be engineered.However, a series of challenges still has to be addressed before the large scale use and production of bacterial biohybrids: to start with, it has yet to be shown that selective attachment can occur even in protein rich natural environments, since most binding strategies have only been applied Concluding, we can say that the field of bacterial hybrid swimmers opens many promising ways to couple custom adaptable cargos to one of evolution's masterpieces, the bacterium. Even today, bacteria play a major role in modern biotech, and we dare to predict that the bacterial biohybrids will increase this even further.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer, AK, and handling Editor declared their shared affiliation.


Feedback brings a fresh perspective and improvement in any organization. Health professionals (HPs) lose insight of the gaps in medical care. The views of student nurses can help improve systems. The objective of this study was to assess the views of our student nurses and how they perceive the way the doctors and HPs work in our hospital and comment on training, attitudes, care pathways, teamwork, and what needed to be improved.A proforma based qualitative study was carried out at the Nurses’ Training Centre of PAF Hospital and Fazaia Medical College, Islamabad, from January to March 2020. After approval, a semi-structured proforma with open and closed ended questions was administered, in English and Urdu. The results were analyzed by comparative numbers and percentages for each question and descriptive responses were grouped in recurring themes and analyzed for content and their constructive value.Out of 85 nursing cadets, the proforma could be administered to 61(M=38(62.3%) and F=23(37.7%). Most were FSc with 26% graduates. Majority of the female students’ main reason for joining was to serve humanity, unlike most males. According to gender many responses were interestingly different. Majority of females thought male doctors were better (86%). Only 36% said the doctors were sincere in care of patients. Most thought that we needed to improve patient counseling. Most thought the seniors treated them unfairly, but bullying was negligible. They wanted the senior HPs to improve their attitudes and ensure adequate equipment in the wards. They were worried about personal security from patients and relatives. Dedicated mental health services to deal with stress of witnessing every day misery and death was suggested.Doctors need to improve their counseling skills and should talk more to the patients and their relatives. They should acknowledge the nursing students and improve teamwork. Belittling them in front of others harms their self-efficacy. Simple corrections like punctuality, ownership of their patients and improvement of equipment and systems can improve patient care. One of the greatest strengths of Nurses training all over the world is their direct involvement in the care of the patients almost from the very first day.2As many of us have observed, and has been proven, that the newly inducted health professionals are motivated, empathetic and altruistic. But over the years they lose these essential qualities.5Feedback from lay people or juniors often brings a fresh perspective and improvement. These feedbacks have content, construct and predictive validity.10Based on the above surmises, the objective of this study was to administer a survey to our student nurses and assess their views about how they perceive the way the doctors and senior HPs work in our hospital. The emphasis was to comment on attitudes of HPs regarding training, care pathways, teamwork, and what needed to be improved.This was a proforma based qualitative exploratory study conducted at the Nurses’ Training Centre of Pakistan Air Force (PAF) Hospital and Fazaia Medical College, Islamabad, from January to March 2020. Approval from Institutional Review Board (IRB/01/3/07/2020) was obtained. A semi-structured proforma with simple open and closed ended questions was administered. The questions were both in English and Urdu, and replies could also be in both languages (Annexure 1). It was anonymously filled and consent taken.The first section of the proforma noted the demographics and education with the basic baseline questions to provide a general background of each cadet. This helped to provide a better understanding of this cohort, and hence correlate with their perceptions. Then there were sections about their views and perceptions regarding: 1, the doctors they worked with; 2, the senior nurses and administrative staff, commenting on their attitudes and what needed to be improved; 3, what needed to be improved in the hospitals and patient care; 4; lastly, a section for free expression of views (Annexure 1).The results were analyzed by finding percentages and frequencies for numerical variables, or as frequency or percentages for categorical variables for each closed question and descriptive responses of open ended questions were grouped in recurring themes and analyzed for content and their constructive value. They were also cross-analyzed for correlation with gender and other demographic information provided, using Microsoft Excel.Frivolous responses and personal problems were identified but not included in the evaluation reports. Although they were shared with the tutors to determine their nature and address appropriately, ensuring that their genuine grievances are heard.11At the time of study, there were 85 nursing cadets of PAF Medical Services enrolled. The proforma could only be administered to 61 of them, the rest being on temporary duties or leave. The sex ratio was M=38(62.3%) and F=23(37.7%). A summary of their demographics and basic data are given in At the end of the Q 3 , Q 4 (what do they think about their own nursing seniors) and Q 6 (Anything else you want to say) it was encouraged to give free opinions. The main themes, answers and the percentages are given in Why you came to nursing? Views about doctors? Doctors need to improve? About your senior nurses? How to improve patient care? Free opinions and answers to open ended questions are summarised in The nursing cadets also mentioned some administrative problems related to the service. These were noted and conveyed to the senior administrators separately. They included points like: excuse of non-clinical duties, separate rooms for admitted staff in the hospital, and some others.The first section of the proforma explores the demographics of our cohort of the newer nurses, which has been found to be useful16The Question 1 in the survey asked why they wanted to join nursing in the PAF . Altruis16the HOs had the best attitude and working relationship with nurses. The consultants ignored them, and this made the teamwork less than optimum. Consultants, as leaders, have to acknowledge the student nurses and make them a useful part of the teams in the care of the patients, which has been reported.Question 2 was important and asked the views of the students regarding the doctors, with whom they worked. Overall they thought the Consultants were best ‘doctors’ (87%), compared to House officers-HOs 23% and Trainees-TRs 17%. This can be expected as the expertise of Consultants was an obvious choice for being selected. About 86% of female students thought that male doctors were better at their job, as compared to only 37% of male students. This gender bias which has been observed previously in other studies as well.an overwhelming majority wanted the doctors to improve the way they talk to the patients, and to be polite. This has been pointed out by so many studies which emphasize the need for empathetic communication skills. Mindfulness-based empathy training (MBET) leads to an increase in empathy.Punctuality was again found to be lacking, which can perhaps be improved by better role modeling and better institutional culture.Again the female students thought that female doctors need more improvement. They also thought that doctors should be nice to student nurses in the wards and 86% wanted to be appreciated for the work they do, which helps in team building, motivation and self-efficacy of the learners.21When asked in Question 3, what the doctors need to improve; As a pleasant surprise only a very small number mentioned being subjected to bullying. Although bullying and abuse has been reported.27Question 4 addressed the attitudes of the senior nurses, tutors and managers. Majority thought that they treat them badly (73%) and unfairly (61%). During the feedback bullying was another direct question which was asked. Bullying is a critical issue, since it is linked with nurse attrition and eventually to their morale.Almost all (92%) thought the patient care needs improvement. We expected that having more doctors and fewer patients would receive a yes vote. However, only 22% and 39% thought this was necessary. Most wanted doctors to do better (62%), better nursing attitudes (67%), more equipment (72%) and improving in-patient care systems (71%). This was a most insightful assessment from such a young group and reported from other studies.28Question 5 was important to know, holistically, about the important aspects of improving the hospital care. to give any harsh feedback separately and not in front of the patients. It belittled them. This decreases confidence; better techniques can be used. The ‘feedback sandwich technique’ provided at the bedside are most useful to the student’s learning.The second important theme was that doctors lack in the way they communicate with the patients and their relatives. The teams discuss the disease at length with each other but do not involve the patients and their carers in the discussions. They also need to care for the private and public patients equally, and irrespective of the status; a simple observation which senior doctors need to reflect on.29The last part of the survey asked for free comments . One thepatients and their relatives also need to follow a code of ethics. This should be implemented and unruly behaviour should be checked immediately to prevent from escalating.doctors’ practices were also insightful. In some wards the rounds were carried out by different doctors every day. This often caused confusion about their main doctor. Regarding the nursing care, clear defining of roles of each member of the ward team was pointed out. This effects job satisfaction, role conflict and ambiguity.31The section 6 of the survey was an invitation to give free comments. It was mentioned that, not only the HPs of the hospital, but the The provision of psychological support to student nurses was also mentioned. A dedicated service for them to deal with their day to day to psychological trauma of death and suffering has to be in place.If only we would listen to them actively.It is surprising how these young student nurses provided such astute observations which were equal to some high powered and expensive studies. Today’s students are wise and observant, and are not afraid to participate in improvement of the patient care. Information from such questionnaires can provide timely feedback and enable administrators to identify and correct organizational factors.This being first study of its type, it has some limitations. The study was conducted in one nursing institute and therefore, the findings can only be used to this specific participant group.Doctors need to improve their counseling skills and should talk more to the patients and their relatives. They should also acknowledge the nursing students and take them along to improve the teamwork. Belittling them in front of others on the ward harms their self-efficacy and capacity to function maximally. Simple corrections like punctuality, ownership of their patients and improvement of systems can enhance the quality of care.SAS: Conception and design, entering, analysis and interpretation of data, drafting the article, literature search, referencing and revising critically.HZ: Facilitating administration of proforma, collection of data, revision of draft, literature search.JA: Improvement of proforma, analysis and interpretation of data, literature search, intellectual input and revision of draft.RQ: Development of proforma, analysis of results, intellectual input, revision of draft.SN: Analysis of results, corrections & revision of draft, intellectual input.CAS: Conception and design, administering the survey, analysis and acquisition of data, interpretation of data, revising the draft, final approval, agreement to be accountable for all aspects of the work, corresponding author.