Neighbourhood factors and tuberculosis incidence in Cape Town: A negative binomial regression and spatial analysis.

OBJECTIVES: Although the link between poverty and tuberculosis (TB) is widely recognised, limited studies have investigated the association between neighbourhood factors and TB incidence. Since the factors influencing different episodes of TB might be different, this study focused on the first episode of TB disease (first-episode TB). METHODS: All first episodes in previously linked and geocoded TB notification data from 2007 to 2015 in Cape Town, South Africa, were aggregated at the neighbourhood level and merged with the 2011 census data. We conducted an ecological study to assess the association between neighbourhood incidence of first-episode TB and neighbourhood factors (total TB burden [all episodes] in the previous year, socioeconomic index, mean household size, mean age, and percentage males) using a negative binomial regression. We also examined the presence of hotspots in neighbourhood TB incidence with the Global Moran's I statistic and assessed spatial dependency in the association between neighbourhood factors and TB incidence using a spatial lag model. RESULTS: The study included 684 neighbourhoods with a median first-episode TB incidence rate of 114 (IQR: 0-345) per 100,000 people. We found lower neighbourhood socioeconomic index (SEI), higher neighbourhood total TB burden, lower neighbourhood mean household size, and lower neighbourhood mean age were associated with increased neighbourhood first-episode TB incidence. Our findings revealed a hotspot of first-episode TB incidence in Cape Town and evidence of spatial dependency in the association between neighbourhood factors and TB incidence. CONCLUSION: Neighbourhood TB burden and SEI were associated with first-episode TB incidence, and there was spatial dependency in this association. Our findings can inform targeted interventions to reduce TB in high-risk neighbourhoods, thereby reducing health disparities and promoting health equity.

Primary healthcare workers at risk during COVID-19: An analysis of infections in HIV service providers in five districts of South Africa.

BACKGROUND: Protecting healthcare workers (HCWs) from COVID-19 is a global priority. Anova Health Institute (Anova) is the PEPFAR (US President's Emergency Plan for AIDS Relief) District Support Partner for the Johannesburg, Cape Town, Sedibeng, Capricorn and Mopani districts in South Africa, operating in public sector primary healthcare facilities. At the time of the emergence of COVID-19, Anova employed close to 4 000 people: 41% community health workers (CHWs), 23% data staff, 20% nurses and doctors, 12% management/support and 5% allied HCWs. OBJECTIVES: To describe rates of COVID-19 diagnosis in Anova-employed HCWs in five districts. METHODS: Employees exposed to, tested for or diagnosed with COVID-19 were required to report the event. These reports were compiled into a database to monitor the impact of COVID-19 on the workforce. We kept a timeline of key events occurring at national and district level, including Anova's policies and their implementation, that was used to describe organisational response. We described the number of confirmed cases, cumulative incidence rates and testing rates, broken down by district and job category. We estimated expected deaths and the effect on time off work. RESULTS: Of Anova employees, 14% (n=562) were diagnosed with COVID-19 by the end of September 2020. Cumulative incidence was highest in Sedibeng (29%) and lowest in Mopani (5%). All HCWs experienced high incidences: data staff 17%, allied HCWs 16%, CHWs 14%, nurses and doctors 13%, and management/support 11%. At the peak of the epidemic, for 5 weeks, >5% of employees were unable to work owing to exposure or infection, significantly disrupting service delivery. The additional administrative burden on managers was substantial. CONCLUSIONS: It is critical that all cadres of HCWs are protected in the workplace, including in primary care settings, where better structuresare needed to perform risk assessments and conduct outbreak investigations. CHWs and data staff may be at higher risk owing to poor infrastructure, limited power to negotiate working conditions, and limited experience of infection prevention and control. Their working conditions must be improved to reduce their risk.

Neuronal clusterin expression is associated with cognitive protection in amyotrophic lateral sclerosis.

AIMS: Clusterin is a topologically dynamic chaperone protein with the ability to participate in both intra- and extacellular proteostasis. Clusterin has been shown to be upregulated in the spinal cord of patients with amyotrophic lateral sclerosis (ALS) and has been shown to protect against TDP-43 protein misfolding in animal and cell models. Previous studies have demonstrated an association between the pathological burden of TDP-43 misfolding and cognitive deficits in ALS, demonstrating high specificity, but correspondingly low sensitivity owing to a subset of individuals with no evidence of cognitive deficits despite a high burden of TDP-43 pathology, called mismatch cases. METHODS: Hypothesizing that differences in the ability to cope with protein misfolding in these cases may be due to differences in expression of protective mechanisms such as clusterin expression, we assessed the spatial expression of clusterin and another chaperone protein, HspB8, in post mortem brain tissue of mismatch cases. We employed a modified in situ hybridization technique called BaseScope, with single cell, single transcript resolution. RESULTS: Mismatch cases demonstrated differential spatial expression of clusterin, with a predominantly neuronal pattern, compared to cases with cognitive manifestations of their TDP-43 pathology who demonstrated a predominantly glial distribution of expression. CONCLUSIONS: Our data suggest that, in individuals with TDP-43 pathology, predominantly neuronal expression of clusterin in extra-motor brain regions may indicate a cell protective mechanism delaying clinical manifestations such as cognitive dysfunction.

Conjugal amyotrophic lateral sclerosis: a case report from Scotland.

BACKGROUND: Conjugal amyotrophic lateral sclerosis is rare, with significant effects on psychological and care needs. We report a case of conjugal amyotrophic lateral sclerosis disease from central Scotland. This case is particularly unusual as both patients were diagnosed within an 18-month period and experienced the disease simultaneously, with similar symptomatology and progression. CASE PRESENTATION: Patient A was a 71-year-old man who presented with unilateral arm weakness and wasting. Patient B was a 68-year-old woman who presented with unilateral shoulder and elbow weakness. Diagnosis of amyotrophic lateral sclerosis was made within a few months of presentation in both cases, based on typical clinical symptomatology together with supportive neurophysiological testing. Interventions included enteral feeding and non-invasive ventilation. The time period between symptom onset and death was 5 years for Patient A and 3.5 years for Patient B. CONCLUSION: This case illustrates two main points: the care issues surrounding cases of conjugal neurological disease, and the psychological issues in these patients. There are significant care issues arising when co-habiting couples both develop severe functionally limiting neurological diseases at the same time. The more slowly progressive nature of Patient A's disease may be at least partially explained by the support he was able to receive from Patient B before she developed symptoms. Secondly, there are important psychological effects of living with someone with the same - but more advanced - progressive and incurable neurological disease. Thus, Patient B was reluctant to have certain interventions that she had observed being given to her husband. Lastly, no plausible shared environmental risk factors were identified, implying that the co-occurrence of ALS in this couple was a random association.

Gist-based illusions within and across stimulus modalities in autism spectrum disorder.

Some studies have reported a low rate of false recognition (FR) in individuals with autism spectrum disorder (ASD) relative to non-autistic comparison participants (CPs). This finding, however, has not always been replicated and the source of the discrepancy remains unknown. We hypothesised that poor episodic memory functions may account for this finding. We used an adapted version of the Deese, Roediger and McDermott paradigm which presents lists of words, pictures or word-picture pairs to obtain measures of performance which reflect episodic [hits and false alarms (FAs)] and semantic (FR) memory functions. Results showed a decreased rate of FR in ASD individuals with lists of words which rose above the rate seen in non-autistic CPs with lists of word-picture pairs. This increased rate of FR in ASD was accompanied by a parallel increase in hits and a decrease in FA which reached a similar level in the two groups. Poor episodic memory functions may prevent individuals with ASD from acquiring item information which in turn precludes the formation of semantic links between items. This could render them less prone to FR.

Social cognition in neurodegenerative disorders: a systematic review.

Social cognitive neuroscience is the study of the neurobiological systems underlying effective social behaviour. The neural processes supporting effective social interactions in everyday life and the consequences of dysfunction in these processes have been the focus of intense research over the last two decades. It is becoming increasingly apparent that the identification of social cognitive deficits in neurodegenerative conditions and their neural basis may provide a better understanding of the behavioural changes observed in these disorders. In addition, accumulating data suggest that detection of early impairment in social cognitive skills may aid in the early diagnosis of cognitive or behavioural impairment in some of these disorders, and may even play a role in the investigation of new therapeutic options. In this review, we outline the basic components of social cognitive processing, provide a systematic review of the literature pertaining to common neurodegenerative conditions, discuss current controversies and make recommendations for future research.

Right hemisphere dysfunction and emotional processing in ALS: an fMRI study.

Emotional processing may be abnormal in amyotrophic lateral sclerosis (ALS). Our aim was to explore functional anatomical correlates in the processing of aversive information in ALS patients. We examined the performance of nine non-demented ALS patients and 10 healthy controls on two functional MRI (fMRI) tasks, consisting of an emotional attribution task and a memory recognition task of unpleasant versus neutral stimuli. During the emotional decision task, subjects were asked to select one of three unpleasant or neutral words. During the memory task, subjects were asked to recognize words presented during the previous task. Controls showed, as expected, greater activation in the right middle frontal gyrus during selection of unpleasant than neutral words, and a greater activation mainly in right-sided cerebral areas during the emotional recognition task. Conversely, patients showed a general increase in activation of the left hemisphere, and reduced activation in right hemisphere in both emotional tasks. Such findings may suggest extra-motor neurodegeneration involving key circuits of emotions, mostly negative, commonly involved in FTD.

Inorganic structures in space group P31m; coordinate analysis and systematic prediction of new ferroelectrics.

The 62 entries listed in ICSD release 2009/1 under polar space group P31m correspond to 31 families of inorganic crystal structures, some with only one member. Coordinate analysis reveals, over a wide confidence range, 11 of these families as ferroelectric candidates. One includes the well known improper ferroelectric GASH (guanidinium aluminum sulfate hexahydrate), [(C(NH(2))(3))Al(SO(4))(2)(H(2)O)(6)], another the previously predicted ferroelectric CsNO(3) phase II. Those remaining include K(3)Nb(3)B(2)O(12), the minerals schairerite, galeite and lizardite 1T, LaNi(5)D(6) and gamma-CaNi(5)D(6.1), Ca(OCl)(2)Ca(OH)(2), [N(CH(3))(4)](2)Mo(3)S(13), Li(17)Ag(3)Sn(6) and Cs(3)As(5)O(9). Candidate selection is based upon detecting an approach by the reported atomic arrangement to the symmetry of a corresponding nonpolar supergroup. A further 13 families are typified by their reduced predictive properties, with four others likely to remain polar at higher temperatures and the remaining three noted as having a unit cell larger than reported or a misassigned space group. The primary sources of uncertainty in structurally based predictions of ferroelectricity are the reliability of the underlying structural determination and the upper limit assigned to the cationic displacement magnitudes required to achieve supergroup symmetry.

EFNS guidelines on the use of neuroimaging in the management of motor neuron diseases.

BACKGROUND AND PURPOSE: These European Federation of Neurological Societies guidelines on neuroimaging of motor neuron diseases (MNDs) are designed to provide practical help for the neurologists to make appropriate use of neuroimaging techniques in patients with MNDs, which ranges from diagnostic and monitoring aspects to the in vivo study of the pathobiology of such conditions. METHODS: Literature searches were performed before expert members of the Task Force wrote proposal. Then, consensus was reached by circulating drafts of the manuscript to the Task Force members and by discussion of the classification of evidence and recommendations. RESULTS AND CONCLUSIONS: The use of conventional MRI in patients suspected of having a MND is yet restricted to exclude other causes of signs and symptoms of MN pathology [class IV, level good clinical practice point (GCPP)]. Although the detection of corticospinal tract hyperintensities on conventional MRI and a T2-hypointense rim in the pre-central gyrus can support a pre-existing suspicion of MND, the specific search of these abnormalities for the purpose of making a firm diagnosis of MND is not recommended (class IV, level GCPP). At present, advanced neuroimaging techniques, including diffusion tensor imaging and proton magnetic resonance spectroscopic imaging, do not have a role in the diagnosis or routine monitoring of MNDs yet (class IV, level GCPP). However, it is strongly advisable to incorporate measures derived from these techniques into new clinical trials as exploratory outcomes to gain additional insights into disease pathophysiology and into the value of these techniques in the (longitudinal) assessment of MNDs (class IV, level GCPP).

Atomic displacements at and order of all phase transitions in multiferroic YMnO3 and BaTiO3.

Coordinate analysis of the multiple phase transitions in hexagonal YMnO(3) leads to the prediction of a previously unknown aristotype phase, with the resulting phase-transition sequence: P6(3)'cm'(e.g.) <--> P6(3)cm <--> P6(3)/mcm <--> P6(3)/mmc <--> P6/mmm. Below the Néel temperature T(N) approximately = 75 K, the structure is antiferromagnetic with the magnetic symmetry not yet determined. Above T(N) the P6(3)cm phase is ferroelectric with Curie temperature T(C) approximately = 1105 K. The nonpolar paramagnetic phase stable between T(C) and approximately 1360 K transforms to a second nonpolar paramagnetic phase stable to approximately 1600 K, with unit-cell volume one-third that below 1360 K. The predicted aristotype phase at the highest temperature is nonpolar and paramagnetic, with unit-cell volume reduced by a further factor of 2. Coordinate analysis of the three well known phase transitions undergone by tetragonal BaTiO(3), with space-group sequence R3m <--> Amm2 <--> P4mm <--> Pm3m, provides a basis for deriving the aristotype phase in YMnO(3). Landau theory allows the I <--> II, III <--> IV and IV <--> V phase transitions in YMnO(3), and also the I <--> II phase transition in BaTiO(3), to be continuous; all four, however, unambiguously exhibit first-order characteristics. The origin of phase transitions, permitted by theory to be second order, that are first order instead have not yet been thoroughly investigated; several possibilities are briefly considered.

SOD1 and cognitive dysfunction in familial amyotrophic lateral sclerosis.

BACKGROUND: Sporadic Amyotrophic Lateral Sclerosis (sALS) is associated with frontotemporal dementia (ALS-FTD) or milder deficits of cognitive (predominantly executive) dysfunction (ALSCi) in some patients. Some forms of familial ALS (FALS) have a family history of FTD, ALS-FTD, or both, but there have been few reports of ALS-FTD in FALS patients with mutations of the gene superoxide dismutase-1 (SOD1 FALS). The aim of this study was to test the hypothesis that ALSCi may be found in non-SOD1 FALS, but that SOD1 FALS patients would show little or no evidence of cognitive change. METHODS: A neuropsychological test battery was administered to 41 SALS patients, 35 control participants, 7 FALS patients with a SOD1 mutation (SOD1 FALS) and 10 FALS patients without a SOD1 mutation (non-SOD1 FALS). RESULTS: Relative to control participants, non-SOD1 FALS patients had impaired performance on written verbal fluency and confrontation naming, and reported higher levels of executive behavioural problems. These deficits were absent in SOD1 FALS patients. SALS patients performed poorer than controls only on the Graded Naming Test. All ALS groups had higher levels of behavioural apathy and emotional lability than were found in control participants. Cognitive domains of memory, receptive language, and visuospatial perception were spared. Groups were matched for age, gender, premorbid full-scale IQ, anxiety and depression. DISCUSSION: Individuals with SOD1 gene mutations are less likely to have significant cognitive changes compared to non-SOD1 FALS patients. Cognitive abnormalities in ALS are heterogeneous and may reflect underlying genetic variations rather than a simple spectrum of extra-motor involvement.

Emotional Lability in MND: Relationship to cognition and psychopathology and impact on caregivers.

Emotional Lability (EL) is a well recognized symptom of cortico-bulbar pathway dysfunction in Motor Neuron Disease/Amyotrophic Lateral Sclerosis (MND/ALS), and is reported to occur in 19-49% of patients. The Emotional Lability Questionnaire (ELQ), is specifically designed to detect EL as reported by MND patients and as observed by their carers. The aims of this study were to 1) validate the Italian version of the ELQ; 2) investigate the relationship between EL and presence of cognitive dysfunction; 3) investigate the relationship between EL and presence of psychopathology. Forty one MND patients, 39 caregivers and respective control groups composed of 39 subjects and 39 partners/friends were tested. The Italian version of the ELQ was found to have good psychometric properties. Seventy-one per cent of patients reported suffering from EL. Correlations were found between bulbar involvement and EL, and between bulbar involvement and low performance on tests of fluid intelligence and working memory. However, the cognitive profile did not correlate with any aspect of EL. The findings suggests that damage to different neurological pathways underlie cognitive change and EL, which supports the concept of MND/ALS as a multisystem disorder. Moreover the outcomes suggest that EL affects patients' everyday life with the increased anxiety and emotional frailty. The findings suggest that those involved in the care of MND patients should be more aware of the effects of EL in the management of the disease.

Inorganic structures in space group P3m1; coordinate analysis and systematic prediction of new ferroelectrics.

ICSD Release 2007/1 contains 47 families of inorganic crystal structures, some single-member only, within the 311 entries listed under the polar space group P3m1. Coordinate analysis reveals 12 such families to be candidate ferroelectrics, over a range of confidence levels. Selection is based on the detection of an approach to nonpolar supergroup symmetry, within specified limits, by the atomic arrangement as reported in a confirmed polar space group. The primary source of uncertainty in such predictions is the reliability of the underlying structural determination. The candidates include In(2)ZnS(4), TlSn(2)F(5), Cu(7)Te(4), NaMnSe(2), Na(2)In(2)(Mo(3)O(8))(MoO(4))(2), Nb(3)Br(7)S, Nb(3)TeI(7), fencooperite, Bi(HCOO)(3), Li(NpO(2))(CO(3))(H(2)O)(2), LiPtD(0.66) and Ag(3)(MoO(3)F(3))(Ag(3)(MoO(4))Cl). A total of 20 structures examined are likely to be nonpolar, a further 20 have reduced predictive properties and three others are more likely to retain P3m1 symmetry over a wide thermal range. Substantial uncertainties associated with many of the listed 163 CdI(2), 69 ZnS and 10 SiC polytype structures, together with their low potential for use as possible ferroelectrics, led to their exclusion from fuller analysis.

Two case studies illustrating how relatively selective hippocampal lesions in humans can have quite different effects on memory.

Two patients, with magnetic resonance imaging (MRI)-confirmed relatively selective hippocampal damage, showed distinct patterns of performance on tests of recall, item recognition, and associative recognition. Patient AC showed a mean bilateral volume reduction of the hippocampus of 28%, but displayed no memory deficit. Both recall and recognition memory were unimpaired. In contrast, patient PR, who showed a mean bilateral hippocampal volume reduction of 59%, was more consistently impaired on recall than recognition tests, although his recognition scores were highly variable. Patients AC and PR illustrate how variable the memory deficit following seemingly selective hippocampal damage can be in humans. They highlight the need for more sophisticated imaging in future studies if the human hippocampus' role in memory is to be fully identified.

Prevalence of depression in a 12-month consecutive sample of patients with ALS.

There is an impression both in clinical practice and in research literature that patients with amyotrophic lateral sclerosis (ALS) possess 'heroic stoicism with a low frequency of depression'. Reliance on specific interview methods may have contributed to differing estimates of mood disorder in people with ALS. The objective of the current study was to compare prevalence rates of depression and anxiety in ALS using different assessment tools. The Beck Depression Inventory (BDI), The Hospital Anxiety and Depression Scale (HADS) and the Spielberger State-Trait Anxiety Inventory (STAI) were sent to a 12-month consecutive sample of 190 patients with ALS attending a tertiary referral clinic in the UK. Data were collected from 104 patients with ALS. Using BDI scores, 44% were categorized as not depressed, 37% were mild-moderately depressed, 13% were moderately-severely depressed, and 6% were severely depressed. In contrast, the HADS depression subscale identified 75% as not depressed, 13% were in the borderline range, and 13% were categorized as meeting 'caseness' for depression. Twenty-five percent of the patients were using antidepressant medication. The estimated prevalence of mood disorder amongst patients with ALS may vary significantly depending on the measure used.

Systematic prediction of new ferroelectrics in space group R3. II.

Release 2006/1 of the Inorganic Crystal Structure Database contains 155 entries under space group R3. Atomic coordinate analysis of the first 81 structures, with 52 different structure types, in Part I [Abrahams (2006). Acta Cryst. B62, 26-41] identified a total of 18 new types that satisfy the structural criteria for ferroelectricity, five that are more likely to have or undergo a transition to 3m symmetry, 19 more likely to be or undergo a transition to nonpolar symmetry and ten with a lower property predictability. Coordinate analysis of the remaining 71 entries with 54 different structure types in Part II leads to 11 materials including Al(4)B(6)O(15), PbTa(3)(PO(4))(P(2)O(7))(3.5), the KCd(4)Ga(5)S(12) family, the LiZnPO(4) family, Ca(3)Nb(1.95)O(8)V(0.05) and Mn(4)Ta(2)O(9) as new candidates which satisfy the structural criteria, together with the three known ferroelectrics Na(3)MoO(3)F(3), Pb(2)ScTaO(6), and RbTi(2)(PO(4))(3) at 6.2 GPa. Two additional ferroelectric predictions are at a lower level of confidence. The analysis also reveals nine materials, two of which are isostructural, that more likely belong or are capable of undergoing a transition to crystal class 3m. There are 14 additional structure types which are more likely to be nonpolar or undergo a transition to nonpolarity, ten have reduced predictive properties, with a further nine for which the space group is expected to remain R3 over the full thermal stability range. The increasing use of methods for identifying overlooked inversion centers in structural determinations may be extended by using coordinate analysis for detecting additional commonly overlooked symmetry elements.