Modeling fine-grained spatio-temporal pollution maps with low-cost sensors.

The use of air quality monitoring networks to inform urban policies is critical especially where urban populations are exposed to unprecedented levels of air pollution. High costs, however, limit city governments' ability to deploy reference grade air quality monitors at scale; for instance, only 33 reference grade monitors are available for the entire territory of Delhi, India, spanning 1500 sq km with 15 million residents. In this paper, we describe a high-precision spatio-temporal prediction model that can be used to derive fine-grained pollution maps. We utilize two years of data from a low-cost monitoring network of 28 custom-designed low-cost portable air quality sensors covering a dense region of Delhi. The model uses a combination of message-passing recurrent neural networks combined with conventional spatio-temporal geostatistics models to achieve high predictive accuracy in the face of high data variability and intermittent data availability from low-cost sensors (due to sensor faults, network, and power issues). Using data from reference grade monitors for validation, our spatio-temporal pollution model can make predictions within 1-hour time-windows at 9.4, 10.5, and 9.6% Mean Absolute Percentage Error (MAPE) over our low-cost monitors, reference grade monitors, and the combined monitoring network respectively. These accurate fine-grained pollution sensing maps provide a way forward to build citizen-driven low-cost monitoring systems that detect hazardous urban air quality at fine-grained granularities.

Post-vaccination outcomes in association with four COVID-19 vaccines in the Kingdom of Bahrain.

With the emergence of new SARS-Cov2 variants, critical questions have arisen about: (1) the effectiveness of the available COVID-19 vaccines developed to protect against the original Wuhan (wild type) variant and (2) the magnitude and clinical consequences of post-vaccination infections in the context of the Delta variant of SARS-Cov2. While some "real world" experiences with various vaccines have been reported, to our knowledge, few have examined comparative outcomes of various vaccines in one country as new SARS-CoV-2 variants have emerged. Here we present an analysis of COVID-19 related outcomes from a national database in Bahrain, a country with a total population of 1.51 million, where four vaccines were deployed (total vaccinated = 1,003,960 adults): AstraZeneca (AZ/Covishield), Pfizer/BioNtech, Sinopharm and Sputnik V. We compare the four vaccines, based on the following post-vaccination outcomes: SARS-CoV-2 infections, hospitalisations, ICU admissions and deaths, compared to unvaccinated individuals. We conclude that the four vaccines used in Bahrain were effective in significantly reducing all four COVID-19 related outcomes compared to unvaccinated individuals, prior to, and during the period when the Delta variant predominated in the country. However, compared to the three other vaccines, individuals vaccinated with Sinopharm vaccine had a higher risk of post-vaccination infections, hospitalisations and ICU admissions (e.g., 6.94%, 2.24%, 1.99% and 1.52% of COVID-19 cases of Sinopharm, Sputnik V, Pfizer and Covishield recipients, respectively, required hospitalisation versus 13.66% of COVID-19 cases among unvaccinated individuals); however, given the confounding factors, this needs to be confirmed by further studies. We find no evidence of biased selection for any vaccine, but note waning protection of the Pfizer/BioNtech vaccine during the January to June 2021 period in the age > 60 y cohort; however, this cannot be distinguished from the overall fall in hospitalisations overall. Our findings support the value of vaccination in preventing COVID-19 related outcomes, provide real world estimates on the outcomes and frequencies of post-vaccination infections for the four vaccines, which may inform vaccine selection in the context of the Delta variant across the globe.

Increasing Interaction of amygdalar afferents with GABAergic interneurons between birth and adulthood.

Previous work in animal models has shown that projections from the basolateral amygdala (BLA) progressively infiltrate the medial prefrontal cortex (mPFC) from birth to adulthood, with the most dramatic sprouting occurring during the postweanling period. GABAergic (gamma-aminobutyric acidergic) interneurons in the human homolog of the rat mPFC have been implicated in the pathophysiology of schizophrenia, an illness with an onset that is delayed until late adolescence. Here we investigated the interaction of BLA fibers with mPFC GABAergic interneurons from postnatal day 6 (P6) to P120 using anterograde tracing and immunocytochemistry. We found a 3-fold increase in axosomatic and an 8-fold increase in axo-dendritic contacts in both layers II and V of the mPFC. Ultrastructural analysis using a colloidal gold immunolocalization demonstrated that the greatest proportion of BLA appositions were with GABA-negative spines (30.8%) and GABA-positive dendritic shafts (35.5%). Although GABA-negative interactions demonstrated well-defined axo-spinous synapses, membrane specializations could not be identified with confidence in GABA-positive elements. Our findings suggest that GABAergic interneurons are major targets for BLA fibers projecting to the mPFC. The establishment of this circuitry, largely during adolescence, may contribute to the integration of emotional responses with attentional and other cognitive processes mediated within this region during corticolimbic development.

DNA fragmentation is increased in non-GABAergic neurons in bipolar disorder but not in schizophrenia.

UNLABELLED: Apoptosis is thought to contribute to neuronal loss in bipolar disorder and schizophrenia, although empiric evidence in support of this idea has been lacking. In this study, we investigated whether or not apoptosis is associated with GABAergic interneurons in the anterior cingulate cortex in schizophrenia (n=14) and bipolar disorder (n=14) when compared to normal controls (n=14). A double-labeling technique using the Klenow method of in situ end-labeling (ISEL) of single-stranded DNA breaks was combined with an in situ hybridization localization of mRNA for the 67 kDa isoform of glutamate decarboxylase (GAD67) and applied to the anterior cingulate cortex of 14 normal controls, 14 schizophrenics, and 14 patients with bipolar disorder matched for age and postmortem interval. An increase in Klenow-positive, GAD67-negative nuclei were observed in layer V/VI of patients with bipolar disorder, but not schizophrenics. Klenow-positive cells that were also positive for GAD67 mRNA did not show differences in either patient group. CONCLUSIONS: This is the first demonstration that there is more DNA fragmentation in cells showing no detectable GAD67 mRNA in patients with bipolar disorder than in schizophrenics or controls. These findings suggest that non-GABAergic cells may be selectively vulnerable to oxidative stress in patients with bipolar disorder.

Long-term effects of amygdala GABA receptor blockade on specific subpopulations of hippocampal interneurons.

Growing evidence indicates that the amygdala modulates hippocampal functions. To test the hypothesis that this modulation may involve long-lasting effects on interneuronal networks in the hippocampus, changes in the expression of neurochemical markers specific for different interneuronal subpopulations were assessed in adult rats 96 h following acute infusion of low doses of the GABAA receptor antagonist picrotoxin into the amygdala. The numerical density (Nd) of somata showing immunoreactivity (IR) for parvalbumin (PVB) was decreased in dentate gyrus (DG) and the CA4-2 region, while that of calretinin (CR)-IR was decreased in DG and CA2. The Nd of calbindin D28k (CB)-IR somata was decreased in CA3-2. The densities of axon terminals arising from PVB-IR and cholecystokinin (CCK)-IR basket neurons were also altered, with those of CCK-IR terminals increased across all sectors, while PVB-IR terminals were decreased only in the CA region. Increases in CCK-IR terminals were paralleled by increases of terminals with IR for the 65-kD isoform of glutamate decarboxylase (GAD65). Mixed-effects statistical models, adapted specifically for these analyses, indicated that perturbations of amygdalar inputs to the hippocampus significantly alter the drive that hippocampal PVB-, CR-, and CB-IR neurons within the dentate gyrus/CA4 region exercise on CCK-IR terminals within the same region as well as in CA3-1. These results suggest that amygdalar modulation of specific neuronal subpopulations may induce lasting and far-reaching changes in the hippocampus during normal functioning, as well as in diseases involving a disruption of amygdalar activity. In particular, changes in specific interneuronal markers within selective hippocampal sectors detected in the present results are strikingly similar to those reported in this region in schizophrenia. These similarities suggest that, in this disease, a disruption of GABAergic transmission within the amygdala may play a significant role in the induction of abnormalities in the hippocampus.

DNA fragmentation decreased in schizophrenia but not bipolar disorder.

BACKGROUND: Apoptosis is thought to play a role in neuronal pathology in schizophrenia and bipolar disorder. METHODS: To test this hypothesis, the Klenow method for in situ end-labeling of single-stranded DNA breaks was applied to anterior cingulate cortex from 18 healthy controls, 18 schizophrenic subjects, and 10 bipolar subjects. RESULTS: An unexpected reduction (71%) in Klenow-positive nuclei was found in schizophrenic but not in bipolar cortexes. CONCLUSIONS: To our knowledge to date, this is the first demonstration that there is much less DNA fragmentation in individuals with schizophrenia than in healthy controls and bipolar subjects, which raises a key question as to whether this alteration represents an adaptive or nonadaptive change in the regulation of intracellular signaling and mitochondrial oxidative pathways associated with apoptosis.

Amygdalo-cortical sprouting continues into early adulthood: implications for the development of normal and abnormal function during adolescence.

Adolescence is a critical stage for the development of emotional maturity and diverse forms of psychopathology. The posterior basolateral nucleus of the amygdala is known to mediate fear and anxiety and is important in assigning emotional valence to cognitive processes. The medial prefrontal cortex, a homologue of the human anterior cingulate cortex, mediates emotional, attentional, and motivational behaviors at the cortical level. We postulate that the development of connectivity between these two corticolimbic regions contributes to an enhanced integration of emotion and cognition during the postnatal period. In order to characterize the development of this relay, injections of the anterograde tracer biocytin were stereotaxically placed within the posterior basolateral nucleus of the amygdala of rats at successive postnatal time points (postnatal days 6-120). Labeled fibers in the medial prefrontal cortex were evaluated using a combination of brightfield, confocal, and electron microscopy. We found that the density of labeled fibers originating from the posterior basolateral nucleus shows a sharp curvilinear increase within layers II and V of the anterior cingulate cortex and the infralimbic subdivisions of medial prefrontal cortex during the late postweanling period. This increase was paralleled by a linear rise in the number of axospinous and axodendritic synapses present in the neuropil. Based on these results, we propose that late maturation of amygdalo-cortical connectivity may provide an anatomical basis for the development and integration of normal and possibly abnormal emotional behavior during adolescence and early adulthood.