Pre-eclampsia and risk of early-childhood asthma: A register study with sibling comparison and an exploration of intermediate variables

Background: We aimed to study whether pre-eclampsia is associated with childhood asthma, allergic and non-Allergic asthma, accounting for family factors and intermediate variables. Methods: The study population comprised 779 711 children born in 2005-2012, identified from Swedish national health registers (n = 14 823/7410 exposed to mild/moderate and severe pre-eclampsia, respectively). We used Cox regression to estimate the associations of mild/moderate and severe pre-eclampsia with incident asthma, before and after age 2 years. Cox regressions were controlled for familial factors using sibling comparisons, then stratified on high and low risk for intermediate variables: caesarean section, prematurity and small for gestational age. We used logistic regression for allergic and non-Allergic prevalent asthma at 6 years as a measure of more established asthma. Results: The incidence of asthma in children was 7.7% (n = 60 239). The associations varied from adjusted hazard ratio (adjHR) 1.11, 95% confidence interval (CI): 1.00, 1.24 for mild/moderate pre-eclampsia and asthma at >2 years age, to adjHR 1.78, 95% CI: 1.64, 1.95 for severe pre-eclampsia and asthma at <2 years age. Sibling comparisons attenuated most estimates except for the association between severe pre-eclampsia and asthma at <2 years age (adjHR 1.45, 95% CI: 1.10, 1.90), which also remained when stratifying for the risk of intermediates. Mild/moderate and severe pre-eclampsia were associated with prevalent non-Allergic (but not allergic) asthma at 6 years, with adjusted odds ratio (adjOR) 1.17, 95% CI: 1.00, 1.36 and adjOR 1.51, 95% CI: 1.23, 1.84, respectively. Conclusions: We found evidence that severe, but not mild/moderate, pre-eclampsia is associated with asthma regardless of familial factors and confounders

Early-Life Adversity Due to Bereavement and Inflammatory Diseases in the Next Generation: A Population Study in Transgenerational Stress Exposure

Emerging evidence suggests that trauma experienced in childhood has negative transgenerational implications for offspring mental and physical health. We aimed to investigate whether early-life adversity experienced as bereavement is associated with chronic inflammatory health in offspring. The study population included 3 generations of Swedish families with a base population of 453,516 children (generation 3) born in 2001-2012. Exposure was defined as the middle generation's (generation 2) experiencing bereavement in childhood due to the death of a parent (generation 1). Outcomes in generation 3 included 2 diagnoses of inflammatory diseases, including asthma, allergic diseases, eczema, and autoimmune diseases. Survival analysis was used to identify causal pathways, including investigation of mediation by generation 2 mood disorders and socioeconomic status (SES). We found that early-life bereavement experienced by women was associated with early-onset offspring asthma (hazard ratio = 1.15, 95% confidence interval: 1.08, 1.23); mediation analysis revealed that 28%-33% of the association may be mediated by SES and 9%-20% by mood disorders. Early-life bereavement experienced by men was associated with autoimmune diseases in offspring (hazard ratio = 1.31, 95% confidence interval: 1.06, 1.62), with no evidence of mediation. In conclusion, adversity experienced early in life may contribute to an increased risk of inflammatory diseases which is partly mediated by mood disorders and SES

The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread “natural experiment” of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic

Some methods for blindfolded record linkage

BACKGROUND: The linkage of records which refer to the same entity in separate data collections is a common requirement in public health and biomedical research. Traditionally, record linkage techniques have required that all the identifying data in which links are sought be revealed to at least one party, often a third party. This necessarily invades personal privacy and requires complete trust in the intentions of that party and their ability to maintain security and confidentiality. Dusserre, Quantin, Bouzelat and colleagues have demonstrated that it is possible to use secure one-way hash transformations to carry out follow-up epidemiological studies without any party having to reveal identifying information about any of the subjects – a technique which we refer to as "blindfolded record linkage". A limitation of their method is that only exact comparisons of values are possible, although phonetic encoding of names and other strings can be used to allow for some types of typographical variation and data errors. METHODS: A method is described which permits the calculation of a general similarity measure, the n-gram score, without having to reveal the data being compared, albeit at some cost in computation and data communication. This method can be combined with public key cryptography and automatic estimation of linkage model parameters to create an overall system for blindfolded record linkage. RESULTS: The system described offers good protection against misdeeds or security failures by any one party, but remains vulnerable to collusion between or simultaneous compromise of two or more parties involved in the linkage operation. In order to reduce the likelihood of this, the use of last-minute allocation of tasks to substitutable servers is proposed. Proof-of-concept computer programmes written in the Python programming language are provided to illustrate the similarity comparison protocol. CONCLUSION: Although the protocols described in this paper are not unconditionally secure, they do suggest the feasibility, with the aid of modern cryptographic techniques and high speed communication networks, of a general purpose probabilistic record linkage system which permits record linkage studies to be carried out with negligible risk of invasion of personal privacy

Selective cyclooxygenase-2 silencing mediated by engineered E. coli and RNA interference induces anti-tumour effects in human colon cancer cells

Colorectal cancer (CRC) has an elevated incidence worldwide and represents one of the most aggressive human tumours. Many experimental data provide the evidence of a strong association between cyclooxygenase-2 (COX-2) enzyme overexpression and colon tumorigenesis. Furthermore, it has been demonstrated that the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs, a class of COX-2 inhibitors), partially protects patients from CRC development and progression. Unfortunately, NSAIDs have been shown to induce severe side effects in chronically treated patients and, therefore, new strategies for selective COX-2 blockade are needed. In this paper we present an innovative COX-2 silencing approach mediated by RNA Interference (RNAi) which is a mechanism we have already described as a powerful tool to knockdown COX-2 protein in CRC cells. In particular, we developed an improved method to gain a highly selective COX-2 silencing in CRC cells by a tumour-dependent expression of anti-COX-2 short hairpin RNA (shCOX-2). Moreover, we efficiently delivered shCOX-2 expressing vectors in CRC cells, in vitro and ex vivo, by using engineered Escherichia coli strains, capable of infecting and invading human tumour cells (InvColi). Combining the highly selective shCOX-2 expression and the delivery of COX-2 silencers mediated by InvColi strains, we obtained a strong reduction of both proliferative and invasive behaviour of tumour cells and we also confirmed the pivotal role of COX-2 overexpression for the survival of CRC cells. Finally, ex vivo data showed a global anti-inflammatory and anti-tumour effect elicited by COX-2 silencing

Risk factors for non-atopic asthma/wheeze in children and adolescents: a systematic review.

BACKGROUND: The study of non-atopic asthma/wheeze in children separately from atopic asthma is relatively recent. Studies have focused on single risk factors and had inconsistent findings. OBJECTIVE: To review evidence on factors associated with non-atopic asthma/wheeze in children and adolescents. METHODS: A review of studies of risk factors for non-atopic asthma/wheeze which had a non-asthmatic comparison group, and assessed atopy by skin-prick test or allergen-specific IgE. RESULTS: Studies of non-atopic asthma/wheeze used a wide diversity of definitions of asthma/wheeze, comparison groups and methods to assess atopy. Among 30 risk factors evaluated in the 43 studies only 3 (family history of asthma/rhinitis/eczema, dampness/mold in the household, and lower respiratory tract infections in childhood) showed consistent associations with non-atopic asthma/wheeze. No or limited period of breastfeeding was less consistently associated with non-atopic asthma/wheeze. The few studies examining the effects of overweight/obesity and psychological/social factors showed consistent associations. We used a novel graphical presentation of different risk factors for non-atopic asthma/wheeze, allowing a more complete perception of the complex pattern of effects. CONCLUSIONS: More research using standardized methodology is needed on the causes of non-atopic asthma

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

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Measurement of top quark–antiquark pair production in association with a W or Z boson in pp collisions at √s=8 TeV

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Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV

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