Tackling health inequalities in primary care: an exploration of GPs’ experience at the frontline

In Scotland, life expectancy and health outcomes are strongly tied to socioeconomic status. Specifically, socioeconomically deprived areas suffer disproportionately from high levels of premature multimorbidity and mortality. To tackle these inequalities in health, challenges in the most deprived areas must be addressed. One avenue that merits attention is the potential role of general medical practitioners (GPs) in helping to address health inequalities, particularly due to their long-term presence in deprived communities, their role in improving patient and population health, and their potential advocacy role on behalf of their patients. GPs can be seen as what Lipsky calls ‘street-level bureaucrats’ due to their considerable autonomy in the decisions they make surrounding individual patient needs, yet practising under the bureaucratic structure of the NHS. While previous research has examined the applicability of Lipsky’s framework to the role of GPs, there has been very little research exploring how GPs negotiate between the multiple identities in their work, how GPs ‘socially construct’ their patients, how GPs view their potential role as ‘advocate’, and what this means in terms of the contribution of GPs to addressing existing inequalities in health. Using semi-structured interviews, this study explored the experience and views of 24 GPs working in some of Scotland’s most deprived practices to understand how they might combat this growing health divide via the mitigation (and potential prevention) of existing health inequalities. Participants were selected based on several criteria including practice deprivation level and their individual involvement in the Deep End project, which is an informal network comprising the 100 most deprived general practices in Scotland. The research focused on understanding GPs’ perceptions of their work including its broader implications, within their practice, the communities within which they practise, and the health system as a whole. The concept of street-level bureaucracy proved to be useful in understanding GPs’ frontline work and how they negotiate dilemmas. However, this research demonstrated the need to look beyond Lipsky’s framework in order to understand how GPs reconcile their multiple identities, including advocate and manager. As a result, the term ‘street-level professional’ is offered to capture more fully the multiple identities which GPs inhabit and to explain how GPs’ elite status positions them to engage in political and policy advocacy. This study also provides evidence that GPs’ social constructions of patients are linked not only to how GPs conceptualise the causes of health inequalities, but also to how they view their role in tackling them. In line with this, the interviews established that many GPs felt they could make a difference through advocacy efforts at individual, community and policy/political levels. Furthermore, the study draws attention to the importance of practitioner-led groups—such as the Deep End project—in supporting GPs’ efforts and providing a platform for their advocacy. Within this study, a range of GPs’ views have been explored based on the sample. While it is unclear how common these views are amongst GPs in general, the study revealed that there is considerable scope for ‘political GPs’ who choose to exercise discretion in their communities and beyond. Consequently, GPs working in deprived areas should be encouraged to use their professional status and political clout not only to strengthen local communities, but also to advocate for policy change that might potentially affect the degree of disadvantage of their patients, and levels of social and health inequalities more generally.

The relationship between early and intermediate level spatial vision during typical development and in autism spectrum disorder

Certaines recherches ont investigué le traitement visuel de bas et de plus hauts niveaux chez des personnes neurotypiques et chez des personnes ayant un trouble du spectre de l’autisme (TSA). Cependant, l’interaction développementale entre chacun de ces niveaux du traitement visuel n’est toujours pas bien comprise. La présente thèse a donc deux objectifs principaux. Le premier objectif (Étude 1) est d’évaluer l’interaction développementale entre l’analyse visuelle de bas niveaux et de niveaux intermédiaires à travers différentes périodes développementales (âge scolaire, adolescence et âge adulte). Le second objectif (Étude 2) est d’évaluer la relation fonctionnelle entre le traitement visuel de bas niveaux et de niveaux intermédiaires chez des adolescents et des adultes ayant un TSA. Ces deux objectifs ont été évalué en utilisant les mêmes stimuli et procédures. Plus précisément, la sensibilité de formes circulaires complexes (Formes de Fréquences Radiales ou FFR), définies par de la luminance ou par de la texture, a été mesurée avec une procédure à choix forcés à deux alternatives. Les résultats de la première étude ont illustré que l’information locale des FFR sous-jacents aux processus visuels de niveaux intermédiaires, affecte différemment la sensibilité à travers des périodes développementales distinctes. Plus précisément, lorsque le contour est défini par de la luminance, la performance des enfants est plus faible comparativement à celle des adolescents et des adultes pour les FFR sollicitant la perception globale. Lorsque les FFR sont définies par la texture, la sensibilité des enfants est plus faible comparativement à celle des adolescents et des adultes pour les conditions locales et globales. Par conséquent, le type d’information locale, qui définit les éléments locaux de la forme globale, influence la période à laquelle la sensibilité visuelle atteint un niveau développemental similaire à celle identifiée chez les adultes. Il est possible qu’une faible intégration visuelle entre les mécanismes de bas et de niveaux intermédiaires explique la sensibilité réduite des FFR chez les enfants. Ceci peut être attribué à des connexions descendantes et horizontales immatures ainsi qu’au sous-développement de certaines aires cérébrales du système visuel. Les résultats de la deuxième étude ont démontré que la sensibilité visuelle en autisme est influencée par la manipulation de l’information locale. Plus précisément, en présence de luminance, la sensibilité est seulement affectée pour les conditions sollicitant un traitement local chez les personnes avec un TSA. Cependant, en présence de texture, la sensibilité est réduite pour le traitement visuel global et local. Ces résultats suggèrent que la perception de formes en autisme est reliée à l’efficacité à laquelle les éléments locaux (luminance versus texture) sont traités. Les connexions latérales et ascendantes / descendantes des aires visuelles primaires sont possiblement tributaires d’un déséquilibre entre les signaux excitateurs et inhibiteurs, influençant ainsi l’efficacité à laquelle l’information visuelle de luminance et de texture est traitée en autisme. Ces résultats supportent l’hypothèse selon laquelle les altérations de la perception visuelle de bas niveaux (local) sont à l’origine des atypies de plus hauts niveaux chez les personnes avec un TSA.

Safety assessment in primary Mycobacterium tuberculosis smear microscopy centres in Blantyre Malawi: a facility based cross sectional survey

Introduction Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is transmitted mainly through aerosolization of infected sputum which puts laboratory workers at risk in spite of the laboratory workers’ risk of infection being at 3 to 9 times higher than the general public. Laboratory safety should therefore be prioritized and optimized to provide sufficient safety to laboratory workers. Objective To assess the safety for the laboratory workers in TB primary microscopy centres in Blantyre urban. Methodology TB primary microscopy centers in Blantyre urban were assessed in aspects of equipment availability, facility layout, and work practice, using a standardized WHO/AFRO ISO 15189 checklist for the developing countries which sets the minimum safety score at ≥80%. Each center was graded according to the score it earned upon assessment. Results Only one (1) microscopy center out nine (9) reached the minimum safety requirement. Four (4) centers were awarded 1 star level, four (4) centers were awarded 2 star level and only one (1) center was awarded 3 star level. Conclusion In Blantyre urban, 89% of the Tuberculosis microscopy centers are failing to provide the minimum safety to the laboratory workers. Government and other stake holders should be committed in addressing the safety challenges of TB microscopy centres in the country to ensure safety for the laboratory workers. Recommendations It is recommended that the study be conducted at the regional or national level for both public and private laboratories in order to have a general picture of safety in Tb microscopy centres possibly across the country.

The Prevalence of Depression among patients and its detection by Primary Health Care Workers at Matawale Health Centre (Zomba)

Background Little information is available on the prevalence of depression in Malawi in primary health care settings and yet there is increased number of cases of depression presenting at tertiary level in severe form. Aim The aim of the study was to determine the prevalence of depression among patients and its detection by health care workers at a primary health care clinic in Zomba. Methods A cross-sectional survey was done among patients attending outpatient department at Matawale Health Centre, in Zomba from 1st July 2009 through to 31st July 2009. A total of 350 adults were randomly selected using systematic sampling. The “Self Reporting Questionnaire”, a questionnaire measuring social demographic factors and the Structured Clinical Interview for DSM-IV Axis I disorders Non-Patient Version (SCID-NP) were administered verbally to the participants. Findings The prevalence of depression among the patients attending the outpatients department was found to be 30.3% while detection rate of depression by clinician was 0%. Conclusion The results revealed the magnitude of depression which is prevalent in the primary health care clinic that goes undiagnosed and unmanaged. It is therefore recommended that primary health care providers do thorough assessments to address common mental disorders especially depression and they should be educated to recognise and manage depression appropriately at primary care level.

Metastability and dynamics of stem cells: from direct observations to inference at the single cell level

Organismal development, homeostasis, and pathology are rooted in inherently probabilistic events. From gene expression to cellular differentiation, rates and likelihoods shape the form and function of biology. Processes ranging from growth to cancer homeostasis to reprogramming of stem cells all require transitions between distinct phenotypic states, and these occur at defined rates. Therefore, measuring the fidelity and dynamics with which such transitions occur is central to understanding natural biological phenomena and is critical for therapeutic interventions.

While these processes may produce robust population-level behaviors, decisions are made by individual cells. In certain circumstances, these minuscule computing units effectively roll dice to determine their fate. And while the 'omics' era has provided vast amounts of data on what these populations are doing en masse, the behaviors of the underlying units of these processes get washed out in averages.

Therefore, in order to understand the behavior of a sample of cells, it is critical to reveal how its underlying components, or mixture of cells in distinct states, each contribute to the overall phenotype. As such, we must first define what states exist in the population, determine what controls the stability of these states, and measure in high dimensionality the dynamics with which these cells transition between states.

To address a specific example of this general problem, we investigate the heterogeneity and dynamics of mouse embryonic stem cells (mESCs). While a number of reports have identified particular genes in ES cells that switch between 'high' and 'low' metastable expression states in culture, it remains unclear how levels of many of these regulators combine to form states in transcriptional space. Using a method called single molecule mRNA fluorescent in situ hybridization (smFISH), we quantitatively measure and fit distributions of core pluripotency regulators in single cells, identifying a wide range of variabilities between genes, but each explained by a simple model of bursty transcription. From this data, we also observed that strongly bimodal genes appear to be co-expressed, effectively limiting the occupancy of transcriptional space to two primary states across genes studied here. However, these states also appear punctuated by the conditional expression of the most highly variable genes, potentially defining smaller substates of pluripotency.

Having defined the transcriptional states, we next asked what might control their stability or persistence. Surprisingly, we found that DNA methylation, a mark normally associated with irreversible developmental progression, was itself differentially regulated between these two primary states. Furthermore, both acute or chronic inhibition of DNA methyltransferase activity led to reduced heterogeneity among the population, suggesting that metastability can be modulated by this strong epigenetic mark.

Finally, because understanding the dynamics of state transitions is fundamental to a variety of biological problems, we sought to develop a high-throughput method for the identification of cellular trajectories without the need for cell-line engineering. We achieved this by combining cell-lineage information gathered from time-lapse microscopy with endpoint smFISH for measurements of final expression states. Applying a simple mathematical framework to these lineage-tree associated expression states enables the inference of dynamic transitions. We apply our novel approach in order to infer temporal sequences of events, quantitative switching rates, and network topology among a set of ESC states.

Taken together, we identify distinct expression states in ES cells, gain fundamental insight into how a strong epigenetic modifier enforces the stability of these states, and develop and apply a new method for the identification of cellular trajectories using scalable in situ readouts of cellular state.

Primary dengue haemorrhagic fever in patients from northeast of Brazil is associated with high levels of interferon-b during acute phase

Dengue is an acute febrile disease caused by the mosquito-borne dengue virus (DENV) that according to clinical manifestations can be classified as asymptomatic, mild or severe dengue. Severe dengue cases have been associated with an unbalanced immune response characterised by an over secretion of inflammatory cytokines. In the present study we measured type I interferon (IFN-I) transcript and circulating levels in primary and secondary DENV infected patients. We observed that dengue fever (DF) and dengue haemorrhagic fever (DHF) patients express IFN-I differently. While DF and DHF patients express interferon-a similarly (52,71 ± 7,40 and 49,05 ± 7,70, respectively), high levels of circulating IFN-b were associated with primary DHF patients. On the other hand, secondary DHF patients were not able to secrete large amounts of IFN-b which in turn may have influenced the high-level of viraemia. Our results suggest that, in patients from our cohort, infection by DENV serotype 3 elicits an innate response characterised by higher levels of IFN-b in the DHF patients with primary infection, which could contribute to control infection evidenced by the low-level of viraemia in these patients. The present findings may contribute to shed light in the role of innate immune response in dengue pathogenesis.

The role of area-level deprivation and gender in participation in population-based faecal immunochemical test (FIT) colorectal cancer screening

This study aimed to investigate the effects of sex and deprivation on participation in a population-based faecal immunochemical test (FIT) colorectal cancer screening programme. The study population included 9785 individuals invited to participate in two rounds of a population-based biennial FIT-based screening programme, in a relatively deprived area of Dublin, Ireland. Explanatory variables included in the analysis were sex, deprivation category of area of residence and age (at end of screening). The primary outcome variable modelled was participation status in both rounds combined (with “participation” defined as having taken part in either or both rounds of screening). Poisson regression with a log link and robust error variance was used to estimate relative risks (RR) for participation. As a sensitivity analysis, data were stratified by screening round. In both the univariable and multivariable models deprivation was strongly associated with participation. Increasing affluence was associated with higher participation; participation was 26% higher in people resident in the most affluent compared to the most deprived areas (multivariable RR = 1.26: 95% CI 1.21–1.30). Participation was significantly lower in males (multivariable RR = 0.96: 95%CI 0.95–0.97) and generally increased with increasing age (trend per age group, multivariable RR = 1.02: 95%CI, 1.01–1.02). No significant interactions between the explanatory variables were found. The effects of deprivation and sex were similar by screening round. Deprivation and male gender are independently associated with lower uptake of population-based FIT colorectal cancer screening, even in a relatively deprived setting. Development of evidence-based interventions to increase uptake in these disadvantaged groups is urgently required.

Fatigue and Damage Tolerance in Primary Composite Aeronautical Structures

The challenging requirements set on new full composite aeronautical structures are mostly related to the demonstration of damage tolerance capability of their primary structures, required by the airworthiness bodies. And while composite-made structures inherently demonstrate exceptional fatigue properties, when put in real life working conditions, a number of external factors can lead to impact damages thus reducing drastically their fatigue resistance due to fiber delamination, disbonding or breaking. This PhD aims towards contributing to the better understanding of the behavior of the primary composite aeronautical structure after near-edge impacts which are inevitable during the service life of an aircraft. The behavior of CFRP structures after impacts in only one small piece of the big picture which is the certification of CFRP built aircraft, where several other parameters need to be evaluated in order to fulfill the airworthiness requirements. These parameters are also discussed in this PhD thesis in order to give a better understanding of the complex task of CFRP structure certification, in which behavior of the impacted structure plays an important role. An experimental and numerical campaign was carried out in order to determine the level of delamination damage in CFRP specimens after near-edge impacts. By calibrating the numerical model with experimental data, it was possible, for different configurations and energy levels, to predict the extension of a delamination in a CFRP structure and to estimate its residual static strength using a very simple but robust technique. The original contribution of this work to the analysis of CFRP structures is the creation of a model which could be applicable to wide range of thicknesses and stacking sequences of CFRP structures, thus potentially being suitable for industrial application, as well.

Prevention of binge drinking in young adolescents through the promotion of a balanced level of psychological well-being: be-dry

This doctoral thesis presents a project carried out in secondary schools located in the city of Ferrara with the primary objective of demonstrating the effectiveness of an intervention based on Well-Being Therapy (Fava, 2016) in reducing alcohol use and improving lifestyles. In the first part (chapters 1-3), an introduction on risky behaviors and unhealthy lifestyle in adolescence is presented, followed by an examination of the phenomenon of binge drinking and of the concept of psychological well-being. In the second part (chapters 4-6), the experimental study is presented. A three-arm cluster randomized controlled trial including three test periods was implemented. The study involved eleven classes that were randomly assigned to receive well-being intervention (WBI), lifestyle intervention (LI) or not receive intervention (NI). Results were analyzed by linear mixed model and mixed-effects logistic regression with the aim to test the efficacy of WBI in comparison with LI and NI. AUDIT-C total score increased more in NI in comparison with WBI (p=0.008) and LI (p=0.003) at 6-month. The odds to be classified as at-risk drinker was lower in WBI (OR 0.01; 95%CI 0.01–0.14) and LI (OR 0.01; 95%CI 0.01–0.03) than NI at 6-month. The odds to use e-cigarettes at 6-month (OR 0.01; 95%CI 0.01–0.35) and cannabis at post-test (OR 0.01; 95%CI 0.01–0.18) were less in WBI than NI. Sleep hours at night decreased more in NI than in WBI (p = 0.029) and LI (p = 0.006) at 6-month. Internet addiction scores decreased more in WBI (p = 0.003) and LI (p = 0.004) at post-test in comparison with NI. Conclusions about the obtained results, limitations of the study, and future implications are discussed. In the seventh chapter, the data of the project collected during the pandemic are presented and compared with those from recent literature.

Contribution of cytokines to the etiology and progression of Primary Myelofibrosis

Primary Myelofibrosis (PMF) is the end-stage of Philadelphia-negative myeloproliferative neoplasms (MPN) and is characterized by fibrosis and hematopoietic failure in bone marrow, with a consequential migration of the malignant hematopoietic stem cells (HSC) in the spleen where they induce ineffective haematopoiesis. To date, available therapies for PMF are still palliative and do not halt the progression of this neoplasm. During my PhD years, our laboratory investigated the factors promoting the onset and progression of PMF. In our PMF mice model, Gata1low mouse, we studied the role of the interaction of HSC niche with megakaryocytes and HSC localization in the bone marrow during their division and cycle. We observed the inflammation and the main protagonists (LNC-2, CXCL1, and TGF-β) of this process and how their level changes before and after the onset of the disease. We investigated the different megakaryocyte populations in the fibrotic environment in different organs (lung and bone marrow) to define the megakaryocytes implicated in this process. In human samples, we described different ultrastructural abnormalities of megakaryocytes from the bone marrow and the spleen, identifying a possible different metabolism in those two populations. In conclusion, we highlighted the intricated crosstalk between the megakaryocytes, the niche and HSC in PMF. We identified megakaryocytes-dependent cytokines altering the homeostasis of the niche and HSC. Those cytokines could be used as alternative therapeutic targets. Furthermore, we observed different megakaryocytic populations in different organs, providing new prospective on the role of megakaryocytes in different microenvironments.

Angiogenic Effects Of Cryosurgery With Liquid Nitrogen On The Normal Skin Of Rats, Through Morphometric Study.

Cryosurgery is an efficient therapeutic technique used to treat benign and malignant cutaneous diseases. The primary active mechanism of cryosurgery is related to vascular effects on treated tissue. After a cryosurgical procedure, exuberant granulation tissue is formed at the injection site, probably as a result of angiogenic stimulation of the cryogen and inflammatory response, particularly in endothelial cells. To evaluate the angiogenic effects of freezing, as part of the phenomenon of healing rat skin subjected to previous injury. Two incisions were made in each of the twenty rats, which were divided randomly into two groups of ten. After 3 days, cryosurgery with liquid nitrogen was performed in one of incisions. The rats' samples were then collected, cut and stained to conduct histopathological examination, to assess the local angiogenesis in differing moments and situations. It was possible to demonstrate that cryosurgery, in spite of promoting cell death and accentuated local inflammation soon after its application, induces quicker cell proliferation in the affected tissue and maintenance of this rate in a second phase, than in tissue healing without this procedure. These findings, together with the knowledge that there is a direct relationship between mononuclear cells and neovascularization (the development of a rich system of new vessels in injury caused by cold), suggest that cryosurgery possesses angiogenic stimulus, even though complete healing takes longer to occur. The significance level for statistical tests was 5% (p<0,05).

Primary Relapse Site Pattern In Women With Triple-negative Breast Cancer.

Despite the remarkable improvements in breast cancer (BC) characterization, accurate prediction of BC clinical behavior is often still difficult to achieve. Some studies have investigated the association between the molecular subtype, namely the basal-like BC and the pattern of relapse, however only few investigated the association between relapse pattern and immunohistochemical defined triple-negative breast cancers (TNBCs). The aim of this study was to evaluate the pattern of relapse in patients with TNBC, namely the primary distant relapse site. One-hundred twenty nine (129) invasive breast carcinomas with follow-up information were classified according to the molecular subtype using immunohistochemistry for ER, PgR and Her2. The association between TNBC and distant relapse primary site was analyzed by logistic regression. Using multivariate logistic regression analysis patients with TNBC displayed only 0.09 (95% CI: 0.00-0.74; p=0.02) the odds of the non-TNBC patients of developing bone primary relapse. Regarding visceral and lymph-node relapse, no differences between in this cohort were found. Though classically regarded as aggressive tumors, TNBCs rarely development primary relapse in bone when compared to non-TNBC, a clinical relevant fact when investigating a metastasis of an occult or non-sampled primary BC.

Homozygous Inactivating Mutation In Nanos3 In Two Sisters With Primary Ovarian Insufficiency.

Despite the increasing understanding of female reproduction, the molecular diagnosis of primary ovarian insufficiency (POI) is seldom obtained. The RNA-binding protein NANOS3 poses as an interesting candidate gene for POI since members of the Nanos family have an evolutionarily conserved function in germ cell development and maintenance by repressing apoptosis. We performed mutational analysis of NANOS3 in a cohort of 85 Brazilian women with familial or isolated POI, presenting with primary or secondary amenorrhea, and in ethnically-matched control women. A homozygous p.Glu120Lys mutation in NANOS3 was identified in two sisters with primary amenorrhea. The substituted amino acid is located within the second C2HC motif in the conserved zinc finger domain of NANOS3 and in silico molecular modelling suggests destabilization of protein-RNA interaction. In vitro analyses of apoptosis through flow cytometry and confocal microscopy show that NANOS3 capacity to prevent apoptosis was impaired by this mutation. The identification of an inactivating missense mutation in NANOS3 suggests a mechanism for POI involving increased primordial germ cells (PGCs) apoptosis during embryonic cell migration and highlights the importance of NANOS proteins in human ovarian biology.

Ant-caterpillar Antagonism At The Community Level: Interhabitat Variation Of Tritrophic Interactions In A Neotropical Savanna.

Ant foraging on foliage can substantially affect how phytophagous insects use host plants and represents a high predation risk for caterpillars, which are important folivores. Ant-plant-herbivore interactions are especially pervasive in cerrado savanna due to continuous ant visitation to liquid food sources on foliage (extrafloral nectaries, insect honeydew). While searching for liquid rewards on plants, aggressive ants frequently attack or kill insect herbivores, decreasing their numbers. Because ants vary in diet and aggressiveness, their effect on herbivores also varies. Additionally, the differential occurrence of ant attractants (plant and insect exudates) on foliage produces variable levels of ant foraging within local floras and among localities. Here, we investigate how variation of ant communities and of traits among host plant species (presence or absence of ant attractants) can change the effect of carnivores (predatory ants) on herbivore communities (caterpillars) in a cerrado savanna landscape. We sampled caterpillars and foliage-foraging ants in four cerrado localities (70-460 km apart). We found that: (i) caterpillar infestation was negatively related with ant visitation to plants; (ii) this relationship depended on local ant abundance and species composition, and on local preference by ants for plants with liquid attractants; (iii) this was not related to local plant richness or plant size; (iv) the relationship between the presence of ant attractants and caterpillar abundance varied among sites from negative to neutral; and (v) caterpillars feeding on plants with ant attractants are more resistant to ant predation than those feeding on plants lacking attractants. Liquid food on foliage mediates host plant quality for lepidopterans by promoting generalized ant-caterpillar antagonism. Our study in cerrado shows that the negative effects of generalist predatory ants on herbivores are detectable at a community level, affecting patterns of abundance and host plant use by lepidopterans. The magnitude of ant-induced effects on caterpillar occurrence across the cerrado landscape may depend on how ants use plants locally and how they respond to liquid food on plants at different habitats. This study enhances the relevance of plant-ant and ant-herbivore interactions in cerrado and highlights the importance of a tritrophic perspective in this ant-rich environment.

Infratentorial Gray Matter Atrophy And Excess In Primary Craniocervical Dystonia.

Primary craniocervical dystonia (CCD) is generally attributed to functional abnormalities in the cortico-striato-pallido-thalamocortical loops, but cerebellar pathways have also been implicated in neuroimaging studies. Hence, our purpose was to perform a volumetric evaluation of the infratentorial structures in CCD. We compared 35 DYT1/DYT6 negative patients with CCD and 35 healthy controls. Cerebellar volume was evaluated using manual volumetry (DISPLAY software) and infratentorial volume by voxel based morphometry of gray matter (GM) segments derived from T1 weighted 3 T MRI using the SUIT tool (SPM8/Dartel). We used t-tests to compare infratentorial volumes between groups. Cerebellar volume was (1.14 ± 0.17) × 10(2) cm(3) for controls and (1.13 ± 0.14) × 10(2) cm(3) for patients; p = 0.74. VBM demonstrated GM increase in the left I-IV cerebellar lobules and GM decrease in the left lobules VI and Crus I and in the right lobules VI, Crus I and VIIIb. In a secondary analysis, VBM demonstrated GM increase also in the brainstem, mostly in the pons. While gray matter increase is observed in the anterior lobe of the cerebellum and in the brainstem, the atrophy is concentrated in the posterior lobe of the cerebellum, demonstrating a differential pattern of infratentorial involvement in CCD. This study shows subtle structural abnormalities of the cerebellum and brainstem in primary CCD.