IMPROVING ACCESS TO CARE AND CONSENT FOR TRANSGENDER AND GENDER DIVERSE YOUTH IN THE UNITED STATES.

Gender-affirming care (GAC) aims to benefit transgender and gender diverse (TGD) youth. GAC includes access to mental health, medical care, and surgical interventions. However, access to GAC and the youth's ability to consent to GAC is frequently contested. This editorial reviews access to care for TGD youth and discusses perspectives on youth consent for GAC. Pertinent challenges include the ability to provide informed consent within current medical and legal frameworks, mental health and parental concerns, and the long-term effects of GAC. Further research, advocacy, and patient education are warranted to ensure safe access to GAC for TGD youth.

Shodagor women cooperate across domains of work and childcare to solve an adaptive problem.

Across human societies, women's economic production and their contributions to childcare are critical in supporting reproductive fitness for themselves, their spouses and children. Yet, the necessity of performing both work and childcare tasks presents women with an adaptive problem in which they must determine how best to allocate their time and energy between these tasks. Women often use cooperative relationships with alloparents to solve this problem, but whether or not women cooperate across different domains (e.g. work and childcare) to access alloparents remains relatively under-explored. Using social network data collected with Shodagor households in Bangladesh, we show that women who need childcare help in order to work draw on cooperative work partners as potential alloparents, and that all women rely heavily on kin, but not reciprocal cooperation for childcare help. These results indicate that Shodagor women strategize to create work and childcare relationships in ways that help solve the adaptive problem they face. We discuss the implications of our results and the example provided by Shodagor women for a broader understanding of women's cooperative relationships, including the importance of socio-ecological circumstances and gendered divisions of labour in shaping women's cooperative strategies. This article is part of the theme issue 'Cooperation among women: evolutionary and cross-cultural perspectives'.

S1P lyase inhibition prevents lung injury following high pressure-controlled mechanical ventilation in aging mice.

Ventilator-induced Lung Injury (VILI) is characterized by hypoxia, inflammatory cytokine influx, loss of alveolar barrier integrity, and decreased lung compliance. Aging influences lung structure and function and is a predictive factor in the severity of VILI; however, the mechanisms of aging that influence the progression or increased susceptibility remain unknown. Aging impacts immune system function and may increase inflammation in healthy individuals. Recent studies suggest that the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) and the enzyme that degrades it S1P lyase (SPL) may be involved in lung pathologies including acute lung injury. It is unknown whether aging influences S1P and SPL expression that have been implicated in lung inflammation, injury, and cell apoptosis. We hypothesized that aging and injurious mechanical ventilation synergistically impair S1P levels and enhance S1P lyase (SPL) expression that amplifies alveolar barrier damage and diminishes pulmonary function. Young (2-3 mo) and old (20-25 mo) C57BL/6 mice were mechanically ventilated for 2 h using pressure-controlled mechanical ventilation (PCMV) at 45 cmH2O and 35 cmH2O, respectively. We assessed the impact of aging and PCMV on several indications of acute lung injury, immune cell recruitment, S1P levels and SPL activity. Furthermore, we evaluated the protective effects of inhibiting SPL by tetrahydroxybutylimidazol (THI) administration on the negative outcomes associated with aging and mechanical injury. PCMV exacerbated lung injury in old mice and increased neutrophil influx that was further exacerbated due to aging. SPL expression increased in the young and old ventilated mice and the old nonventilated group. THI treatment reduced several of the indicators of lung injury and resulted in elevated S1P levels in lung tissue and plasma from mice that were injured from mechanical ventilation. CD80 and CD206 activation markers of alveolar and interstitial macrophages were also influenced by THI. SPL inhibition may be a viable therapeutic approach for patients requiring mechanical ventilation by preventing or regulating the exaggerated inflammatory response and reducing lung injury.

Microbial contamination in drinking water at public outdoor recreation facilities in New Zealand.

AIM: The aim of our study was to assess the presence and risk of waterborne pathogens in the drinking water of outdoor facilities in New Zealand and track potential sources of microbial contamination in water sources. METHODS AND RESULTS: A serial cross-sectional study with a risk-based sample collection strategy was conducted at 15 public campgrounds over two summer seasons (2011-2012 and 2012-2013). Drinking water supplied to these campgrounds was not compliant with national standards, based on Escherichia coli as an indicator organism, in more than half of the sampling occasions. Campylobacter contamination of drinking water at the campgrounds was likely to be of wild bird origin. Faecal samples from rails (pukeko and weka) were 35 times more likely to return a Campylobacter-positive result compared to passerines. Water treatment using ultraviolet (UV) irradiation or a combination of filtration and UV irradiation or chemicals was more likely to result in water that was compliant with the national standards than water from a tap without any treatment. The use of filters alone was not associated with the likelihood of compliance. CONCLUSIONS: Providing microbiologically safe drinking water at outdoor recreational facilities is imperative to avoid gastroenteritis outbreaks. This requires an in-depth understanding of potential sources of contamination in drinking water sources and the installation of adequate water treatment facilities. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study provides evidence that drinking water without treatment or filter-only treatment in public campgrounds is unlikely to comply with national standards for human consumption and extra water treatment measures such as UV irradiation or chemical treatment are needed.

Acute growth inhibition & toxicity analysis of nano-polystyrene spheres on Raphidocelis subcapitata.

Micro/nano-plastics (MNPs) have been found within many environments and organisms including humans, making them a significant and growing concern. Initial research into the potential detrimental effects these MNPs both from acute and chronic exposure has been ongoing but still requires substantially more data to clarify. This research presents the response of nano-polystyrene (NPS) on Raphidocelis subcapitata, a freshwater alga, under an existing acute toxicity test along with additional analytical techniques to try identifying possible sources of toxicity. R. subcapitata cells were exposed for 72 h to a concentration range of 0-100 mg/l NPS. Growth Inhibition (GI) testing showed the R. subcapitata demonstrated statistically distinct reductions in growth over 72 h at all NPS exposure concentrations while not suffering culture collapse. By the 100 mg/l NPS exposure the R. subcapitata has suffered almost a 33.7% reduction in cell concentration after 72 h compared to control samples. Confocal imaging showed the NPS wasn't permeating into the algal plasma membrane or individual organelles but agglomerated onto the algal cell wall. The agglomeration was irregular but increased in total surface area covered as NPS concentration increases. UV-Vis fluorimetry testing produced a linear response of emission intensities to algae exposed to the 0-100 mg/l range of NPS. However, comparisons of emission intensity values of algae exposed to NPS to emission intensities of pure NPS at identical concentrations showed consistent intensity reduction. This response further indicated NPS agglomerating within the media and onto the alga cells seen from confocal imaging. Finally, Raman spectroscopy on R. subcapitata attempted to distinguish the key 1001 cm-1 peak or other crucial identifier peaks of polystyrene from overall Raman spectra. This was not successful as emissions from algal component (e.g. phenylaniline) completely suppressed the signal region.

Efficacy, safety, and user experience of DIY or open-source artificial pancreas systems: a systematic review.

The do-it-yourself artificial pancreas system (DIYAPS) is a patient-driven initiative with the potential to revolutionise diabetes management, automating insulin delivery with existing pumps and CGM combined with open-source algorithms. Given the considerable interest in this topic within the diabetes community, we have conducted a systematic review of DIYAPS efficacy, safety, and user experience. Following recognised procedures and reporting standards, we identified 10 eligible publications of 730 participants within the peer-reviewed literature. Overall, studies reported improvements in time in range, HbA1c (glycated haemoglobin), reduced hypoglycaemia, and improved quality of life with DIYAPS use. While results were positive, the identified studies were small, and the majority were observational and at high risk of bias. Further research including well-designed randomised trials comparing DIYAPS with appropriate comparators is recommended.

Convergent dental adaptations in the serrations of hypercarnivorous synapsids and dinosaurs.

Theropod dinosaurs are well known for having a ziphodont dentition: serrated, blade-shaped teeth that they used for cutting through prey. Serrations along the carinae of theropod teeth are composed of true denticles, a complex arrangement of dentine, enamel, and interdental folds. This structure would have supported individual denticles and dissipated the stresses associated with feeding. These particular serrations were previously thought to be unique to theropod dinosaurs and some other archosaurs. Here, we identify the same denticles and interdental folds forming the cutting edges in the teeth of a Permian gorgonopsian synapsid, extending the temporal and phylogenetic distribution of this dental morphology. This remarkable instance of convergence not only represents the earliest record of this adaptation to hypercarnivory but also demonstrates that the first iteration of this feature appeared in non-mammalian synapsids. Comparisons of tooth serrations in gorgonopsians with those of earlier synapsids and hypercarnivorous mammals reveal some gorgonopsians acquired a complex tissue arrangement that differed from other synapsids.

Prevalence of Pain on Admission by Level of Cognitive Impairment in Nursing Homes.

PURPOSE: To provide contemporary estimates of pain by level of cognitive impairment among US nursing home residents without cancer. METHODS: Newly admitted US nursing home residents without cancer assessed with the Minimum Data Set 3.0 at admission (2010-2016) were eligible (n=8,613,080). The Cognitive Function Scale was used to categorize level of cognitive impairment. Self-report or staff-assessed pain was used based on a 5-day look-back period. Estimates of adjusted prevalence ratios (aPR) were derived from modified Poisson models. RESULTS: Documented prevalence of pain decreased with increased levels of cognitive impairment in those who self-reported pain (68.9% no/mild, 32.9% severe) and those with staff-assessed pain (50.6% no/mild, 37.2% severe staff-assessed pain). Relative to residents with no/mild cognitive impairment, pharmacologic pain management was less prevalent in those with severe cognitive impairment (self-reported: 51.3% severe vs 76.9% in those with no/mild; staff assessed: 52.0% severe vs 67.7% no/mild). CONCLUSION: Pain was less frequently documented in those with severe cognitive impairment relative to those with no/mild impairments. Failure to identify pain may result in untreated or undertreated pain. Interventions to improve evaluation of pain in nursing home residents with cognitive impairment are needed.

Differences in Staff-Assessed Pain Behaviors among Newly Admitted Nursing Home Residents by Level of Cognitive Impairment.

OBJECTIVE: Pain is common among nursing home residents with cognitive impairment and dementia. Pain is often underdiagnosed and undertreated, which may lead to adverse health outcomes. Nonverbal behaviors are valid indicators of pain, but the extent to which these behavioral expressions vary across levels of cognitive impairment is unknown. This study sought to examine differences in the prevalence of pain behaviors among nursing home residents with varying levels of cognitive impairment. METHODS: The Minimum Data Set, version 3.0, was used to identify newly admitted nursing home residents with staff-assessed pain (2010-2016, n = 1,036,806). Staff-assessed pain behaviors included nonverbal sounds, vocal complaints, facial expressions, and protective body movements or postures over a 5-day look-back period for residents unable or unwilling to self-report pain. The Cognitive Function Scale was used to categorize residents as having no/mild, moderate, or severe cognitive impairment. Modified Poisson models provided adjusted prevalence ratios (aPR) and 95% CIs. RESULTS: Compared to residents with no/mild cognitive impairments (any pain: 48.1%), residents with moderate cognitive impairment (any pain: 42.4%; aPR: 0.94 [95% CI 0.93-0.95]) and severe cognitive impairment (any pain: 38.4%; aPR: 0.86 [95% CI 0.85-0.88]) were less likely to have any pain behavior documented. Vocal pain behaviors were common (43.5% in residents with no/mild cognitive impairment), but less so in those with severe cognitive impairment (20.1%). Documentation of facial expressions and nonverbal pain behaviors was more frequent for residents with moderate and severe cognitive impairment than those with no/mild cognitive impairment. CONCLUSIONS: The prevalence of behaviors indicative of pain differs by level of cognitive impairment. Pain evaluation and management plays an important role in treatment and care outcomes. Future work should examine how practitioners' perceptions of pain behaviors influence their ratings of pain intensity and treatment choices.

Insect swarms can be bound together by repulsive forces.

The cohesion of insect swarms has been attributed to the fact that the resultant internal interactions of the swarming insects produce, on the average, a centrally attractive force that acts on each individual. Here it is shown how insect swarms can also be bound together by centrally forces that on the average are repulsive (outwardly directed from the swarm centres). This is predicted to arise when velocity statistics are heterogeneous (position-dependent). Evidence for repulsive forces is found in laboratory swarms of Chironomus riparius midges. In homogeneous swarms, the net inward acceleration balances the tendency of diffusion (stochastic noise) to transport individuals away from the centre of the swarm. In heterogenous swarms, turbophoresis --the tendency for individuals to migrate in the direction of decreasing kinetic energy-- is operating. The new finding adds to the growing realization that insect swarms are analogous to self-gravitating systems. By acting in opposition to central attraction (gravity), the effects of heterogeneous velocities (energies) are analogous to the effects of dark energy. The emergence of resultant forces from collective behaviours would not be possible if individual flight patterns were themselves unstable. It is shown how individuals reduce the potential for the loose of flight control by minimizing the influence of jerks to which they are subjected.

Prescription analgesia and adjuvant use by pain severity at admission among nursing home residents with non-malignant pain.

OBJECTIVE: We estimated the use of prescribed analgesics and adjuvants among nursing home residents without cancer who reported pain at their admission assessment, in relation to resident-reported pain severity. METHODS: Medicare Part D claims were used to define 3 classes of analgesics and 7 classes of potential adjuvants on the 21st day after nursing home admission (or the day of discharge for residents discharged before that date) among 180,780 residents with complete information admitted between January 1, 2011 and December 9, 2016, with no cancer diagnosis. RESULTS: Of these residents, 27.9% reported mild pain, 46.6% moderate pain, and 25.6% reported severe pain. The prevalence of residents in pain without Part D claims for prescribed analgesic and/or adjuvant medications was 47.3% among those reporting mild pain, 35.7% among those with moderate pain, and 24.8% among those in severe pain. Among residents reporting severe pain, 33% of those ≥ 85 years of age and 35% of those moderately cognitively impaired received no prescription analgesics/adjuvants. Use of all classes of prescribed analgesics and adjuvants increased with resident-reported pain severity, and the concomitant use of medications from multiple classes was common. CONCLUSION: Among nursing home residents with recognized pain, opportunities to improve the pharmacologic management of pain, especially among older residents, and those living with cognitive impairments exist.

Adipose tissue dysfunction in obese horses with equine metabolic syndrome.

BACKGROUND: Obesity is a common feature of equine metabolic syndrome (EMS). In other species, obese adipose tissue shows pathological features such as adipocyte hypertrophy, fibrosis, inflammation and impaired insulin signalling all of which contribute to whole body insulin dysregulation. Such adipose tissue dysfunction has not been investigated in horses. OBJECTIVES: To determine if obese horses with EMS have adipose tissue dysfunction characterised by adipocyte hypertrophy, fibrosis, inflammation and altered insulin signalling. STUDY DESIGN: Cross-sectional post-mortem study. METHODS: Samples of peri-renal (visceral) and retroperitoneal adipose tissue were obtained at post-mortem from healthy horses (n = 9) and horses with EMS (n = 6). Samples were analysed to determine average adipocyte size, fibrotic content and expression of inflammatory and insulin signalling genes. RESULTS: Horses with metabolic syndrome showed marked adipocyte hypertrophy and increased expression of adipokines (leptin) and inflammatory cytokines (TNFα, IL1ß and CCL2) in both adipose tissue depots compared to healthy horses. There were no differences in fibrosis or expression of genes relating to insulin signalling between the groups. MAIN LIMITATIONS: Cases used in this study had advanced EMS and may represent the end stage of the condition; the design of the study is such that we were unable to relate the identified adipose tissue dysfunction to whole body insulin dysregulation. CONCLUSIONS: Horses with obesity and EMS have significant dysfunction of the peri-renal and retroperitoneal adipose tissue that may contribute to whole body insulin dysregulation.

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

OBJECTIVES: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. METHODS: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. RESULTS: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. CONCLUSIONS: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.

Suicide Among Persons With Dementia, Georgia, 2013 to 2016.

INTRODUCTION: Findings from studies examining the relationship between dementia and suicide have been inconsistent. This study examined the characteristics, precipitants, and risk factors for suicide among persons with dementia. METHODS: Data from the Georgia Alzheimer's Disease and Related Dementia registry were linked with 2013 to 2016 data from Georgia Vital Records and Georgia Violent Death Reporting System. Descriptive statistics were calculated and logistic regression was used to examine risk factors for suicide. RESULTS: Ninety-one Georgia residents with dementia who died by suicide were identified. Among decedents with known circumstances, common precipitants included depressed mood (38.7%) and physical health problems (72.6%). Suicide rate among persons with dementia was 9.3 per 100 000 person-years overall and substantially higher among those diagnosed in the past 12 months (424.5/100 000 person-years). Being male, dementia diagnosis before age 65, and a recent diagnosis of dementia independently predicted suicide, but not depression or cardiovascular diseases. CONCLUSION: Prevention strategies that identify at-risk individuals, provide support, and ensure continuity of care for persons diagnosed with dementia may help reduce suicide in this population.

Inflammation and Monocyte Recruitment due to Aging and Mechanical Stretch in Alveolar Epithelium are Inhibited by the Molecular Chaperone 4-phenylbutyrate.

INTRODUCTION: Ventilator-Induced lung injury (VILI) is a form of acute lung injury that is initiated or exacerbated by mechanical ventilation. The aging lung is also more susceptible to injury. Harmful mechanical stretch of the alveolar epithelium is a recognized mechanism of VILI, yet little is known about how mechanical stretch affects aged epithelial cells. Disruption to Endoplasmic Reticulum (ER) homeostasis results in a condition known as ER stress that leads to disruption of cellular homeostasis, apoptosis, and inflammation. ER stress is increased with aging and other pathological stimuli. We hypothesized that age and mechanical stretch increase alveolar epithelial cells' proinflammatory responses that are mediated by ER stress. Furthermore, we believed that inhibition of this upstream mechanism with 4PBA, an ER stress reducer, alleviates subsequent inflammation and monocyte recruitment. METHODS: Type II alveolar epithelial cells (ATII) were harvested from C57Bl6/J mice 2 months (young) and 20 months (old) of age. The cells were cyclically stretched at 15% change in surface area for up to 24 hours. Prior to stretch, groups were administered 4PBA or vehicle as a control. RESULTS: Mechanical stretch and age upregulated ER stress and proinflammatory MCP-1/CCL2 and MIP-1ß/CCL4 chemokine expression in ATIIs. Age-matched and mismatched monocyte recruitment by ATII conditioned media was also quantified. CONCLUSIONS: Age increases susceptibility to stretch-induced ER stress and downstream inflammatory gene expression in a primary ATII epithelial cell model. Administration of 4PBA attenuated the increased ER stress and proinflammatory responses from stretch and/or age and significantly reduced monocyte migration to ATII conditioned media.

Critical evaluation of current data analysis strategies for psychophysiological measures of fear conditioning and extinction in humans.

Fear conditioning and extinction is a construct integral to understanding trauma-, stress- and anxiety-related disorders. In the laboratory, associative learning paradigms that pair aversive with neutral stimuli are used as analogues to real-life fear learning. These studies use physiological indices, such as skin conductance, to sensitively measure rates and intensity of learning and extinction. In this review, we discuss some of the potential limitations in interpreting and analysing physiological data during the acquisition or extinction of conditioned fear. We argue that the utmost attention should be paid to the development of modelling approaches of physiological data in associative learning paradigms, by illustrating the lack of replicability and interpretability of results in current methods. We also show that statistical significance may be easily achieved in this paradigm without more stringent data and data analysis reporting requirements, leaving this particular field vulnerable to misleading conclusions. This review is written so that issues and potential solutions are accessible to researchers without mathematical training. We conclude the review with some suggestions that all laboratories should be able to implement, including visualising the full data set in publications and adopting modelling, or at least regression-based, approaches.

The effect of transportation and lairage on faecal shedding and carcass contamination with Escherichia coli O157 and O26 in very young calves in New Zealand.

The effect of transportation and lairage on the faecal shedding and post-slaughter contamination of carcasses with Escherichia coli O157 and O26 in young calves (4-7-day-old) was assessed in a cohort study at a regional calf-processing plant in the North Island of New Zealand, following 60 calves as cohorts from six dairy farms to slaughter. Multiple samples from each animal at pre-slaughter (recto-anal mucosal swab) and carcass at post-slaughter (sponge swab) were collected and screened using real-time PCR and culture isolation methods for the presence of E. coli O157 and O26 (Shiga toxin-producing E. coli (STEC) and non-STEC). Genotype analysis of E. coli O157 and O26 isolates provided little evidence of faecal-oral transmission of infection between calves during transportation and lairage. Increased cross-contamination of hides and carcasses with E. coli O157 and O26 between co-transported calves was confirmed at pre-hide removal and post-evisceration stages but not at pre-boning (at the end of dressing prior to chilling), indicating that good hygiene practices and application of an approved intervention effectively controlled carcass contamination. This study was the first of its kind to assess the impact of transportation and lairage on the faecal carriage and post-harvest contamination of carcasses with E. coli O157 and O26 in very young calves.

Farm and abattoir sources of Carnobacterium species and implications for lamb meat spoilage.

AIMS: To investigate the transmission route of Carnobacterium from the farm environment to the meat-manufacturing plant and potential risk for meat spoilage. METHODS AND RESULTS: A sheep farm-level survey of Carnobacterium, consisting of 150 environmental and animal (no 100) associated samples, was carried out on two farms. A further 20 lamb carcass samples were taken from an abattoir servicing one of the farms. The majority of Carnobacterium maltaromaticum isolates were associated with fleece followed by hard sheep contact surfaces, rectal-anal mucosal swabs and carcasses. Enterobacterial repetitive intergenic consenus PCR (ERIC-PCR) profiling revealed four distinct ERIC types. Each ERIC type was found on both farms, three of which were also found on lamb carcasses. CONCLUSIONS: Enterobacterial repetitive intergenic consenus PCR was effective at demonstrating within-species variability in C. maltaromaticum. This study provides initial information showing that farm sources maybe an important transmission route of Carnobacterium for contamination of lamb carcasses and subsequently the meat processing environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Data on distribution, diversity, sources and transmission routes for meat product contamination is limited for spoilage bacteria. This study highlights the importance of good hygienic slaughter practices and cleaning routines to remove accumulated detritus from the handling of animals that may lead to cross-contamination.

Langevin dynamics encapsulate the microscopic and emergent macroscopic properties of midge swarms.

In contrast to bird flocks, fish schools and animal herds, midge swarms maintain cohesion but do not possess global order. High-speed imaging techniques are now revealing that these swarms have surprising properties. Here, I show that simple models found on the Langevin equation are consistent with this wealth of recent observations. The models predict correctly that large accelerations, exceeding 10 g, will be common and they predict correctly the coexistence of core condensed phases surrounded by dilute vapour phases. The models also provide new insights into the influence of environmental conditions on swarm dynamics. They predict that correlations between midges increase the strength of the effective force binding the swarm together. This may explain why such correlations are absent in laboratory swarms but present in natural swarms which contend with the wind and other disturbances. Finally, the models predict that swarms have fluid-like macroscopic mechanical properties and will slosh rather than slide back and forth after being abruptly displaced. This prediction offers a promising avenue for future experimentation that goes beyond current quasi-static testing which has revealed solid-like responses.