title: Slowdown and heating of interstellar neutral helium by elastic collisions beyond the heliopause

authors: Swaczyna, P.

subjects: astro-ph.SR

abstract: Direct sampling of interstellar neutral (ISN) atoms close to the Sun enables studies of the very local interstellar medium (VLISM) around the heliosphere. The primary population of ISN helium atoms has, until now, been assumed to reflect the pristine VLISM conditions at the heliopause. Consequently, the atoms observed at 1 au by the Interstellar Boundary Explorer (IBEX) were used to determine the VLISM temperature and velocity relative to the Sun, without accounting for elastic collisions with other species outside the heliopause. Here, we evaluate the effect of these collisions on the primary ISN helium population. We follow trajectories of helium atoms and track their collisions with slowed plasma and interstellar hydrogen atoms ahead of the heliopause. Atoms typically collide a few times in the outer heliosheath, and only ~1.5% of the atoms are not scattered at all. We use calculated differential cross sections to randomly choose scattering angles in these collisions. We estimate that the resulting primary ISN helium atoms at the heliopause are slowed down by ~0.45 km/s⁻¹ and heated by ~1100 K compared to the pristine VLISM. The resulting velocity distribution is asymmetric and shows an extended tail in the antisunward direction. Accounting for this change in the parameters derived from IBEX observations gives the Sun's relative speed of 25.85 km/s⁻¹ and temperature of 6400 K in the pristine VLISM. Finally, this paper serves as a source of the differential cross sections for elastic collisions with helium atoms.

text: Slowdown and heating of interstellar neutral helium by elastic collisions beyond the heliopause Direct sampling of interstellar neutral (ISN) atoms close to the Sun enables studies of the very local interstellar medium (VLISM) around the heliosphere. The primary population of ISN helium atoms has, until now, been assumed to reflect the pristine VLISM conditions at the heliopause. Consequently, the atoms observed at 1 au by the Interstellar Boundary Explorer (IBEX) were used to determine the VLISM temperature and velocity relative to the Sun, without accounting for elastic collisions with other species outside the heliopause. Here, we evaluate the effect of these collisions on the primary ISN helium population. We follow trajectories of helium atoms and track their collisions with slowed plasma and interstellar hydrogen atoms ahead of the heliopause. Atoms typically collide a few times in the outer heliosheath, and only ~1.5% of the atoms are not scattered at all. We use calculated differential cross sections to randomly choose scattering angles in these collisions. We estimate that the resulting primary ISN helium atoms at the heliopause are slowed down by ~0.45 km/s⁻¹ and heated by ~1100 K compared to the pristine VLISM. The resulting velocity distribution is asymmetric and shows an extended tail in the antisunward direction. Accounting for this change in the parameters derived from IBEX observations gives the Sun's relative speed of 25.85 km/s⁻¹ and temperature of 6400 K in the pristine VLISM. Finally, this paper serves as a source of the differential cross sections for elastic collisions with helium atoms.

year: 2021

title: Neuromolecular basis of anomalous feeding behaviour in the valproate rat model of autism

authors: Pal, Tapasya

subjects: Valproate rat model of autism

abstract: Autism spectrum disorder (ASD), which affects circa 1% of the global population, is characterized by impairments in social communication, interaction, language disability, sensory anomalies, repetitive behaviours, and intellectual disability. Aberrant feeding behaviour is a common comorbidity of ASD. ASD individuals often demonstrate extreme food selectivity, refusal, dependence on few very particular food items, neophobia etc. which can lead to nutritional deficiencies affecting development. However, the underlying neurophysiological mechanisms of aberrant food intake in ASD are not well known.

Prenatal exposure to the antiepileptic drug, valproic acid (VPA), leads to autism. The prenatally VPA-exposed rats are model organisms to study ASD and they show ASD-like symptoms of, among others, elevated anxiety and decreased social interaction. Importantly, very little is known about appetite control in these animals. The overall goal of the studies included in this thesis was to identify potential feeding behavioural anomalies and associated neuromolecular changes in the VPA rat model of ASD. We thus hypothesize that ASD is associated with abnormal appetite and reward-driven feeding.

The key factors shaping consumption involve hunger (determines search for calories), satiation (underpins termination of feeding) and reward (consumption for the 'pleasantness' of food, regardless of the energy requirements). Thus, in the first Specific Aim of this thesis, the hunger processing in the VPA animals was investigated. The ad libitum intake of ‘bland’ standard laboratory chow was assessed in VPA versus non-VPA controls maintained continuously on this diet. The adult VPA rats ate less ‘bland’ chow than healthy controls did, and it was coupled with a moderately lower body weight than that of the controls. VPA rats also ate less of the standard chow after acute food deprivation. There was an aberrant change in c-Fos immunoreactivity in key brain sites that govern food intake, including the hypothalamic and brain stem areas, in the VPA animals in contrast to the healthy controls upon food deprivation, which indicates differences in neural processing of hunger in autism. This finding is further supported by a lack of change in expression patterns of feeding-related genes

(including oxytocin (OT), Agouti-related protein (AgRP) and mu opioid receptor (MOR)) upon hunger in the hypothalamus in the VPAs as opposed to the controls. Cumulatively, these findings suggest that hunger processing is altered in the VPA rats.

In the second Specific Aim of this project, intake of rewarding diets in the VPA rats was examined to address whether ASD affects pleasure-driven consumption. In episodic meal consumption paradigms, i.e., in scenarios in which energy non-deprived animals were given a brief and non-habitual access to diets that differ in palatability, the VPA rats were found to consume elevated amounts of tasty liquid and solid diets. These data suggest that VPA rats display not only altered energy homeostatis processing (as shown in Specific Aim 1), but also indicate changes in the regulation of eating for palatability.

Considering the abnormal OT signalling in autism and the fact that OT decreases feeding for energy and feeding for palatability, the third Specific Aim addressed whether VPA rats exhibit heightened sensitivity to exogenously administered OT, a peptide known for its anorexigenic properties. Intraperitoneal OT treatment was found to reduce episodic intake of palatable diets as well as post-energy deprivation intake of ‘bland’ chow; however, the dose needed to generate hypophagia was lower in VPAs than in controls. c-Fos immunohistochemistry revealed that the lower OT dose found to be anorexigenic in VPA rats, was sufficient to affect brain activation in a manner typical for hypophagia, whereas in healthy control rats, it did not induce significant c-Fos changes.

Importantly, OT is involved also in the process of avoidance of toxic foods, i.e., it facilitates the development of a conditioned taste aversion (CTA). Therefore, the goal of the Specific Aim 4, was to assess whether VPA animals display atypical taste aversion acquisition. It was found that VPAs failed to develop aversion to a standard dose of LiCl that induces a CTA in healthy non-ASD controls. In line with the outcome of the behavioural study, the immunohistochemical analysis revealed lower c-Fos-OT colocalization in the PVN in VPAs and a less pronounced broader CTA circuit c-Fos response in ASD animals compared to controls after LiCl treatment.

Taken together, evidence presented in this thesis shows that ASD is associated with abnormal appetite in VPA rats and it offers an insight into the neural basis of this phenomenon. The VPA animals show a slight decrease in intake of standard ‘bland’ chow, an elevated drive to consume palatable tastants, and resistance to taste aversion. These anomalies in feeding behaviours are underpinned by distinct changes in brain activation and gene expression patterns, as well as altered sensitivity to anorexigenic properties of OT, a neuropeptide known to affect other symptoms of ASD, from social deficits to anxiety.

text: Neuromolecular basis of anomalous feeding behaviour in the valproate rat model of autism Autism spectrum disorder (ASD), which affects circa 1% of the global population, is characterized by impairments in social communication, interaction, language disability, sensory anomalies, repetitive behaviours, and intellectual disability. Aberrant feeding behaviour is a common comorbidity of ASD. ASD individuals often demonstrate extreme food selectivity, refusal, dependence on few very particular food items, neophobia etc. which can lead to nutritional deficiencies affecting development. However, the underlying neurophysiological mechanisms of aberrant food intake in ASD are not well known.

Prenatal exposure to the antiepileptic drug, valproic acid (VPA), leads to autism. The prenatally VPA-exposed rats are model organisms to study ASD and they show ASD-like symptoms of, among others, elevated anxiety and decreased social interaction. Importantly, very little is known about appetite control in these animals. The overall goal of the studies included in this thesis was to identify potential feeding behavioural anomalies and associated neuromolecular changes in the VPA rat model of ASD. We thus hypothesize that ASD is associated with abnormal appetite and reward-driven feeding.

The key factors shaping consumption involve hunger (determines search for calories), satiation (underpins termination of feeding) and reward (consumption for the 'pleasantness' of food, regardless of the energy requirements). Thus, in the first Specific Aim of this thesis, the hunger processing in the VPA animals was investigated. The ad libitum intake of ‘bland’ standard laboratory chow was assessed in VPA versus non-VPA controls maintained continuously on this diet. The adult VPA rats ate less ‘bland’ chow than healthy controls did, and it was coupled with a moderately lower body weight than that of the controls. VPA rats also ate less of the standard chow after acute food deprivation. There was an aberrant change in c-Fos immunoreactivity in key brain sites that govern food intake, including the hypothalamic and brain stem areas, in the VPA animals in contrast to the healthy controls upon food deprivation, which indicates differences in neural processing of hunger in autism. This finding is further supported by a lack of change in expression patterns of feeding-related genes

(including oxytocin (OT), Agouti-related protein (AgRP) and mu opioid receptor (MOR)) upon hunger in the hypothalamus in the VPAs as opposed to the controls. Cumulatively, these findings suggest that hunger processing is altered in the VPA rats.

In the second Specific Aim of this project, intake of rewarding diets in the VPA rats was examined to address whether ASD affects pleasure-driven consumption. In episodic meal consumption paradigms, i.e., in scenarios in which energy non-deprived animals were given a brief and non-habitual access to diets that differ in palatability, the VPA rats were found to consume elevated amounts of tasty liquid and solid diets. These data suggest that VPA rats display not only altered energy homeostatis processing (as shown in Specific Aim 1), but also indicate changes in the regulation of eating for palatability.

Considering the abnormal OT signalling in autism and the fact that OT decreases feeding for energy and feeding for palatability, the third Specific Aim addressed whether VPA rats exhibit heightened sensitivity to exogenously administered OT, a peptide known for its anorexigenic properties. Intraperitoneal OT treatment was found to reduce episodic intake of palatable diets as well as post-energy deprivation intake of ‘bland’ chow; however, the dose needed to generate hypophagia was lower in VPAs than in controls. c-Fos immunohistochemistry revealed that the lower OT dose found to be anorexigenic in VPA rats, was sufficient to affect brain activation in a manner typical for hypophagia, whereas in healthy control rats, it did not induce significant c-Fos changes.

Importantly, OT is involved also in the process of avoidance of toxic foods, i.e., it facilitates the development of a conditioned taste aversion (CTA). Therefore, the goal of the Specific Aim 4, was to assess whether VPA animals display atypical taste aversion acquisition. It was found that VPAs failed to develop aversion to a standard dose of LiCl that induces a CTA in healthy non-ASD controls. In line with the outcome of the behavioural study, the immunohistochemical analysis revealed lower c-Fos-OT colocalization in the PVN in VPAs and a less pronounced broader CTA circuit c-Fos response in ASD animals compared to controls after LiCl treatment.

Taken together, evidence presented in this thesis shows that ASD is associated with abnormal appetite in VPA rats and it offers an insight into the neural basis of this phenomenon. The VPA animals show a slight decrease in intake of standard ‘bland’ chow, an elevated drive to consume palatable tastants, and resistance to taste aversion. These anomalies in feeding behaviours are underpinned by distinct changes in brain activation and gene expression patterns, as well as altered sensitivity to anorexigenic properties of OT, a neuropeptide known to affect other symptoms of ASD, from social deficits to anxiety.

year: 2023

title: Outcomes from colonoscopy following referral from New Zealand general practice: a retrospective analysis

authors: Lawrenson, Ross

subjects: Science & Technology

abstract: Background: New Zealand has high rates of colorectal cancer (CRC) but poor outcomes. Most patients with CRC are diagnosed following referral from general practice, where a general practitioner (GP) assesses symptoms according to national guidelines. All referred patients are then re-prioritised by the hospital system. The first objective of this study was to identify what proportion of patients referred by general practice to surgical/gastroenterology at Waikato District Health Board (DHB) had a colonoscopy. The second objective was to determine what proportion of these referrals have an underlying CRC and the factors associated with the likelihood of this diagnosis. 
Methods: This study is a retrospective analysis of e-referral data for patients aged 30–70+ who were referred from 75 general practices to general surgery, gastroenterology or direct to colonoscopy at Waikato DHB, 01 January 2015–31 December 2017. Primary and secondary outcome measures included the proportion and characteristics of patients who were having colonoscopy, and of those, who were diagnosed with CRC. Data were analysed using chi square and logistic regression. 
Results: 6718/20648 (32.5%) patients had a colonoscopy and 372 (5.5%) of these were diagnosed with CRC. The probability of having CRC following a colonoscopy increased with age (p value < 0.001). Females (p value < 0.001), non-Māori (p value < 0.001), and patients with a high suspicion of cancer (HSCan) label originating from their GP were more likely to have a colonoscopy, while the odds ratio of Māori having a colonoscopy was 0.66 (95% CI 0.60–0.73). The odds ratio of a CRC diagnosis following colonoscopy was 1.67 (95% CI 1.35–2.07) for men compared to women, and 2.34 (95% CI 1.70–3.22) for those with a GP HSCan label. Of the 585 patients referred with a GP HSCan, 423 (72.3%) were reprioritised by the hospital and 55 patients had their diagnosis unnecessarily delayed. 
Conclusions: If a GP refers a patient with an HSCan, and the patient receives a colonoscopy, then the likelihood of having CRC is almost 15.0%. This would suggest that these patients should be routinely prioritised without further triage by the hospital. Further research is needed to understand why Māori are less likely to receive a colonoscopy following referral from general practice.

text: Outcomes from colonoscopy following referral from New Zealand general practice: a retrospective analysis Background: New Zealand has high rates of colorectal cancer (CRC) but poor outcomes. Most patients with CRC are diagnosed following referral from general practice, where a general practitioner (GP) assesses symptoms according to national guidelines. All referred patients are then re-prioritised by the hospital system. The first objective of this study was to identify what proportion of patients referred by general practice to surgical/gastroenterology at Waikato District Health Board (DHB) had a colonoscopy. The second objective was to determine what proportion of these referrals have an underlying CRC and the factors associated with the likelihood of this diagnosis. 
Methods: This study is a retrospective analysis of e-referral data for patients aged 30–70+ who were referred from 75 general practices to general surgery, gastroenterology or direct to colonoscopy at Waikato DHB, 01 January 2015–31 December 2017. Primary and secondary outcome measures included the proportion and characteristics of patients who were having colonoscopy, and of those, who were diagnosed with CRC. Data were analysed using chi square and logistic regression. 
Results: 6718/20648 (32.5%) patients had a colonoscopy and 372 (5.5%) of these were diagnosed with CRC. The probability of having CRC following a colonoscopy increased with age (p value < 0.001). Females (p value < 0.001), non-Māori (p value < 0.001), and patients with a high suspicion of cancer (HSCan) label originating from their GP were more likely to have a colonoscopy, while the odds ratio of Māori having a colonoscopy was 0.66 (95% CI 0.60–0.73). The odds ratio of a CRC diagnosis following colonoscopy was 1.67 (95% CI 1.35–2.07) for men compared to women, and 2.34 (95% CI 1.70–3.22) for those with a GP HSCan label. Of the 585 patients referred with a GP HSCan, 423 (72.3%) were reprioritised by the hospital and 55 patients had their diagnosis unnecessarily delayed. 
Conclusions: If a GP refers a patient with an HSCan, and the patient receives a colonoscopy, then the likelihood of having CRC is almost 15.0%. This would suggest that these patients should be routinely prioritised without further triage by the hospital. Further research is needed to understand why Māori are less likely to receive a colonoscopy following referral from general practice.

year: 2021-12-15