Broadband infrastructure, ICT use and firm performance: evidence for UK firms

The recent economics literature has begun to recognise that ICT is a heterogeneous technology altering information storage, processing and communication in distinct ways. In this paper we use the arrival of a new communication technology, ADSL broadband, to study the effects of heterogeneous types of ICT on firm performance. To do so free from endogeneity bias, we construct instruments using postcode-level geographic variation in the infrastructure underlying broadband internet - the pre-existing telephone network. We show that after placing various restrictions on the sample, instruments based on the timing of ADSL broadband enablement and the cable distance to the local telephone exchange satisfy the conditions for instrument relevancy and validity. We find in turn, that ICT causally affects firm size (captured by either sales or employment) but not productivity

Cloud computing and firm growth

Cloud computing has shifted how firms access IT away from investment in fixed capital to pay-on-demand services that facilitate remote and simultaneous use. Using new firm-level data we examine the impact of cloud adoption on firm performance and organizational geography with an IV approach that exploits cross-section and time-series variation in fiber broadband speeds as instruments. Cloud leads younger firms to increase revenue, employment, and productivity, whereas incumbent firms experience no scale effects and weaker productivity gains. Incumbents however undergo restructuring through establishment deaths and fewer births, while both types of firms experience geographic reorganization as activity shifts farther from the headquarters

Estrogen-related and other disease diagnoses preceding Parkinson’s disease

PURPOSE: Estrogen exposure has been associated with the occurrence of Parkinson's disease (PD), as well as many other disorders, and yet the mechanisms underlying these relations are often unknown. While it is likely that estrogen exposure modifies the risk of various diseases through many different mechanisms, some estrogen-related disease processes might work in similar manners and result in association between the diseases. Indeed, the association between diseases need not be due only to estrogen-related factors, but due to similar disease processes from a variety of mechanisms. PATIENTS AND METHODS: All female Parkinson's disease cases between 1982 and 2007 (n = 12,093) were identified from the Danish National Registry of Patients, along with 10 controls matched by years of birth and enrollment. Conditional logistic regressions (CLR) were used to calculate risk of PD after diagnosis of the estrogen-related diseases, endometriosis and osteoporosis, conditioning on years of birth and enrollment. To identify novel associations between PD and any other preceding conditions, CLR was also used to calculate the odds ratios (ORs) for risk of PD for 202 different categories of preceding disease diagnoses. Empirical Bayes methods were used to identify the robust associations from the over 200 associations produced by this analysis. RESULTS: We found a positive association between osteoporosis and osteoporotic fractures and PD (OR = 1.18, 95% confidence interval [CI] of 1.08–1.28), while a lack of association was observed between endometriosis and PD (OR = 1.37, 95% CI 0.99–1.90). Using empirical Bayes analyses, 24 additional categories of diseases, likely unrelated to estrogen exposure, were also identified as potentially associated with PD. CONCLUSION: We identified several novel associations, which may provide insight into common causal mechanisms between the diseases or greater understanding of potential early preclinical signs of PD. In particular, the associations with several categories of mental disorders suggest that these may be early warning signs of PD onset or these diseases (or the causes of these diseases) may predispose to PD.US Public Health Service (R01 NS36711-09); Robert P. and Judith N. Goldberg Foundation; Aarhus University Hospital Department of Clinical Epidemiology's Research Foundatio

Risk factor studies of age-at-onset in a sample ascertained for Parkinson disease affected sibling pairs: a cautionary tale

An association between exposure to a risk factor and age-at-onset of disease may reflect an effect on the rate of disease occurrence or an acceleration of the disease process. The difference in age-at-onset arising from case-only studies, however, may also reflect secular trends in the prevalence of exposure to the risk factor. Comparisons of age-at-onset associated with risk factors are commonly performed in case series enrolled for genetic linkage analysis of late onset diseases. We describe how the results of age-at-onset studies of environmental risk factors reflect the underlying structure of the source population, rather than an association with age-at-onset, by contrasting the effects of coffee drinking and cigarette smoking on Parkinson disease age-at-onset with the effects on age-at-enrollment in a population based study sample. Despite earlier evidence to suggest a protective association of coffee drinking and cigarette smoking with Parkinson disease risk, the age-at-onset results are comparable to the patterns observed in the population sample, and thus a causal inference from the age-at-onset effect may not be justified. Protective effects of multivitamin use on PD age-at-onset are also shown to be subject to a bias from the relationship between age and multivitamin initiation. Case-only studies of age-at-onset must be performed with an appreciation for the association between risk factors and age and ageing in the source population

Risk of Parkinson's disease after tamoxifen treatment

<p>Abstract</p> <p>Background</p> <p>Women have a reduced risk of developing Parkinson's disease (PD) compared with age-matched men. Neuro-protective effects of estrogen potentially explain this difference. Tamoxifen, commonly used in breast cancer treatment, may interfere with the protective effects of estrogen and increase risk of PD. We compared the rate of PD in Danish breast cancer patients treated with tamoxifen to the rate among those not treated with tamoxifen.</p> <p>Methods</p> <p>A cohort of 15,419 breast cancer patients identified from the Danish Breast Cancer Collaborative Group database was linked to the National Registry of Patients to identify PD diagnoses. Overall risk and rate of PD following identification into the study was compared between patients treated with tamoxifen as adjuvant hormonal therapy and patients not receiving tamoxifen. Time-dependent effects of tamoxifen treatment on PD rate were examined to estimate the likely induction period for tamoxifen.</p> <p>Results</p> <p>In total, 35 cases of PD were identified among the 15,419 breast cancer patients. No overall effect of tamoxifen on rate of PD was observed (HR = 1.3, 95% CI: 0.64-2.5), but a PD hazard ratio of 5.1 (95% CI: 1.0-25) was seen four to six years following initiation of tamoxifen treatment.</p> <p>Conclusions</p> <p>These results provide evidence that the neuro-protective properties of estrogen against PD occurrence may be disrupted by tamoxifen therapy. Tamoxifen treatments may be associated with an increased rate of PD; however these effects act after four years, are of limited duration, and the adverse effect is overwhelmed by the protection against breast recurrence conferred by tamoxifen therapy.</p

Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study

Background: The presence of measles virus (MV) RNA in bowel tissue from children with autism spectrum disorders (ASD) and gastrointestinal (GI) disturbances was reported in 1998. Subsequent investigations found no associations between MV exposure and ASD but did not test for the presence of MV RNA in bowel or focus on children with ASD and GI disturbances. Failure to replicate the original study design may contribute to continued public concern with respect to the safety of the measles, mumps, and rubella (MMR) vaccine. Methodology/Principal Findings: The objective of this case-control study was to determine whether children with GI disturbances and autism are more likely than children with GI disturbances alone to have MV RNA and/or inflammation in bowel tissues and if autism and/or GI episode onset relate temporally to receipt of MMR. The sample was an age-matched group of US children undergoing clinically-indicated ileocolonoscopy. Ileal and cecal tissues from 25 children with autism and GI disturbances and 13 children with GI disturbances alone (controls) were evaluated by real-time reverse transcription (RT)-PCR for presence of MV RNA in three laboratories blinded to diagnosis, including one wherein the original findings suggesting a link between MV and ASD were reported. The temporal order of onset of GI episodes and autism relative to timing of MMR administration was examined. We found no differences between case and control groups in the presence of MV RNA in ileum and cecum. Results were consistent across the three laboratory sites. GI symptom and autism onset were unrelated to MMR timing. Eighty-eight percent of ASD cases had behavioral regression. Conclusions/Significance: This study provides strong evidence against association of autism with persistent MV RNA in the GI tract or MMR exposure. Autism with GI disturbances is associated with elevated rates of regression in language or other skills and may represent an endophenotype distinct from other ASD

Rare and Coding Region Genetic Variants Associated With Risk of Ischemic Stroke: The NHLBI Exome Sequence Project

Stroke is the second leading cause of death and the third leading cause of years of life lost. Genetic factors contribute to stroke prevalence, and candidate gene and genome-wide association studies (GWAS) have identified variants associated with ischemic stroke risk. These variants often have small effects without obvious biological significance. Exome sequencing may discover predicted protein-altering variants with a potentially large effect on ischemic stroke risk

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

A Framework for Predicting Memory Errors with a Bayesian Model of Concept Generalization

“Similarity” is often thought to dictate memory errors. For example, in visual memory, memory judgements of lures are related to their psychophysical similarity to targets: an approximately exponential function in stimulus space (Schurgin et al. 2020). However, similarity is ill-defined for more complex stimuli, and memory errors seem to depend on all the remembered items, not just pairwise similarity. Such effects can be captured by a model that views similarity as a byproduct of Bayesian generalization (Tenenbaum &amp; Griffiths, 2001). Here we ask whether the propensity of people to generalize from a set to an item predicts memory errors to that item. We use the “number game” generalization task to collect human judgements about set membership for symbolic numbers and show that memory errors for numbers are consistent with these generalization judgements rather than pairwise similarity. These results suggest that generalization propensity, rather than “similarity”, drives memory errors