A very brief history of interception

Britain is in the process of legislating a new system of control over the interception of communication. The Investigatory Powers Bill, currently being debated in draft form, aims to give an unprecedented level of transparency and accountability to the use of government surveillance powers. In this ‘long read’ piece for the Media Policy Project, LSE PhD student Bernard Keenan provides some historical context on the issue of interception, arguing that the more the law oversees secret activities, the more secretive the law becomes

Investigating the Relationship Between a District’s Tier 2 Attendance Intervention Program and Student Attendance Outcomes

The study will investigate attendance-related outcomes for Fresh Start, a Tier 2 attendance intervention program (AIP) currently being used by the Wingate Public Schools in Massachusetts to collaboratively problem-solve with parents/guardians of elementary school students (Kindergarten through 6th grade) who demonstrate chronic truancy issues. The Fresh Start program is utilized when the requesting school has been unable to make contact with the parent/guardian of a student in order to address the attendance problem via a school meeting. Membership of the Tier 2 AIP team includes school administrators, faculty, and staff, the parent/guardian, and a representative from a community agency that works directly with the parent/guardian in the collaborative problem solving process. In this study, demographic, student achievement, health, and academic services data were examined to investigate changes in attendance patterns following the AIP intervention

Genetic Risk Score Predicting Risk of Rheumatoid Arthritis Phenotypes and Age of Symptom Onset

Cumulative genetic profiles can help identify individuals at high-risk for developing RA. We examined the impact of 39 validated genetic risk alleles on the risk of RA phenotypes characterized by serologic and erosive status.We evaluated single nucleotide polymorphisms at 31 validated RA risk loci and 8 Human Leukocyte Antigen alleles among 542 Caucasian RA cases and 551 Caucasian controls from Nurses' Health Study and Nurses' Health Study II. We created a weighted genetic risk score (GRS) and evaluated it as 7 ordinal groups using logistic regression (adjusting for age and smoking) to assess the relationship between GRS group and odds of developing seronegative (RF- and CCP-), seropositive (RF+ or CCP+), erosive, and seropositive, erosive RA phenotypes. In separate case only analyses, we assessed the relationships between GRS and age of symptom onset. In 542 RA cases, 317 (58%) were seropositive, 163 (30%) had erosions and 105 (19%) were seropositive with erosions. Comparing the highest GRS risk group to the median group, we found an OR of 1.2 (95% CI = 0.8-2.1) for seronegative RA, 3.0 (95% CI = 1.9-4.7) for seropositive RA, 3.2 (95% CI = 1.8-5.6) for erosive RA, and 7.6 (95% CI = 3.6-16.3) for seropositive, erosive RA. No significant relationship was seen between GRS and age of onset.Results suggest that seronegative and seropositive/erosive RA have different genetic architecture and support the importance of considering RA phenotypes in RA genetic studies

Primase-based whole genome amplification

In vitro DNA amplification methods, such as polymerase chain reaction (PCR), rely on synthetic oligonucleotide primers for initiation of the reaction. In vivo, primers are synthesized on-template by DNA primase. The bacteriophage T7 gene 4 protein (gp4) has both primase and helicase activities. In this study, we report the development of a primase-based Whole Genome Amplification (pWGA) method, which utilizes gp4 primase to synthesize primers, eliminating the requirement of adding synthetic primers. Typical yield of pWGA from 1 ng to 10 ng of human genomic DNA input is in the microgram range, reaching over a thousand-fold amplification after 1 h of incubation at 37°C. The amplification bias on human genomic DNA is 6.3-fold among 20 loci on different chromosomes. In addition to amplifying total genomic DNA, pWGA can also be used for detection and quantification of contaminant DNA in a sample when combined with a fluorescent reporter dye. When circular DNA is used as template in pWGA, 108-fold of amplification is observed from as low as 100 copies of input. The high efficiency of pWGA in amplifying circular DNA makes it a potential tool in diagnosis and genotyping of circular human DNA viruses such as human papillomavirus (HPV)

Using discursive approaches to examine the utility and functions of language in public health and health promotion: highlighting social constructions of e-cigarettes

This article uses discursive approaches to examine the utility and functions of language in public health, focusing on social constructions of e-cigarettes. Due to the ambiguity surrounding the use of e-cigarettes, understanding may be negotiated collaboratively through co-construction in talk. Ten participants, three men and seven women aged 26–47 years, took part in two focus groups in Manchester, UK, where they discussed e-cigarettes. Data were analysed using blended discourse analysis, with a view to identifying dominant repertoires used by speakers. Participants drew from two discursive frameworks to communicate perceptions of e-cigarettes: (1) uncertainty and risk and (2) the social acceptability and stigma spectrum. The ambiguity surrounding e-cigarettes was reflected in the linguistic devices used in talk. This article demonstrates the value of drawing on discourse analysis to better understand the impact of health-related communication by providing insight into how existing messages are interpreted, co-constructed, and assigned meaning through shared interactions

A prospective study of androgen levels, hormone-related genes and risk of rheumatoid arthritis

Introduction Rheumatoid arthritis (RA) is more common in females than males and sex steroid hormones may in part explain this difference. We conducted a case–control study nested within two prospective studies to determine the associations between plasma steroid hormones measured prior to RA onset and polymorphisms in the androgen receptor (AR), estrogen receptor 2 (ESR2), aromatase (CYP19) and progesterone receptor (PGR) genes and RA risk. Methods We genotyped AR, ESR2, CYP19, PGR SNPs and the AR CAG repeat in RA case–control studies nested within the Nurses\u27 Health Study (NHS), NHS II (449 RA cases, 449 controls) and the Women\u27s Health Study (72 cases, and 202 controls). All controls were matched on cohort, age, Caucasian race, menopausal status, and postmenopausal hormone use. We measured plasma dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone binding globulin in 132 pre-RA samples and 396 matched controls in the NHS cohorts. We used conditional logistic regression models adjusted for potential confounders to assess RA risk. Results Mean age of RA diagnosis was 55 years in both cohorts; 58% of cases were rheumatoid factor positive at diagnosis. There was no significant association between plasma DHEAS, total testosterone, or calculated free testosterone and risk of future RA. There was no association between individual variants or haplotypes in any of the genes and RA or seropositive RA, nor any association for the AR CAG repeat. Conclusions Steroid hormone levels measured at a single time point prior to RA onset were not associated with RA risk in this study. Our findings do not suggest that androgens or the AR, ESR2, PGR, and CYP19 genes are important to RA risk in women

Recognizable clinical subtypes of obstructive sleep apnea across international sleep centers: a cluster analysis

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesSTUDY OBJECTIVES: A recent study of patients with moderate-severe obstructive sleep apnea (OSA) in Iceland identified three clinical clusters based on symptoms and comorbidities. We sought to verify this finding in a new cohort in Iceland and examine the generalizability of OSA clusters in an international ethnically diverse cohort. METHODS: Using data on 972 patients with moderate-severe OSA (apnea-hypopnea index [AHI] ≥ 15 events per hour) recruited from the Sleep Apnea Global Interdisciplinary Consortium (SAGIC), we performed a latent class analysis of 18 self-reported symptom variables, hypertension, cardiovascular disease, and diabetes. RESULTS: The original OSA clusters of disturbed sleep, minimally symptomatic, and excessively sleepy replicated among 215 SAGIC patients from Iceland. These clusters also generalized to 757 patients from five other countries. The three clusters had similar average AHI values in both Iceland and the international samples, suggesting clusters are not driven by OSA severity; differences in age, gender, and body mass index were also generally small. Within the international sample, the three original clusters were expanded to five optimal clusters: three were similar to those in Iceland (labeled disturbed sleep, minimal symptoms, and upper airway symptoms with sleepiness) and two were new, less symptomatic clusters (labeled upper airway symptoms dominant and sleepiness dominant). The five clusters showed differences in demographics and AHI, although all were middle-aged (44.6-54.5 years), obese (30.6-35.9 kg/m2), and had severe OSA (42.0-51.4 events per hour) on average. CONCLUSIONS: Results confirm and extend previously identified clinical clusters in OSA. These clusters provide an opportunity for a more personalized approach to the management of OSA.National Institutes of Health Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) National Center For Advancing Translational Science

Conditional targeting in mice reveals that hepatic homogentisate 1,2-dioxygenase activity is essential in reducing circulating homogentisic acid and for effective therapy in the genetic disease alkaptonuria.

Alkaptonuria is an inherited disease caused by homogentisate 1,2-dioxygenase (HGD) deficiency. Circulating homogentisic acid (HGA) is elevated and deposits in connective tissues as ochronotic pigment. In this study, we aimed to define developmental and adult HGD tissue expression and determine the location and amount of gene activity required to lower circulating HGA and rescue the alkaptonuria phenotype. We generated an alkaptonuria mouse model using a knockout-first design for the disruption of the HGD gene. Hgd tm1a -/- mice showed elevated HGA and ochronosis in adulthood. LacZ staining driven by the endogenous HGD promoter was localised to only liver parenchymal cells and kidney proximal tubules in adulthood, commencing at E12.5 and E15.5 respectively. Following removal of the gene trap cassette to obtain a normal mouse with a floxed 6th HGD exon, a double transgenic was then created with Mx1-Cre which conditionally deleted HGD in liver in a dose dependent manner. 20% of HGD mRNA remaining in liver did not rescue the disease, suggesting that we need more than 20% of liver HGD to correct the disease in gene therapy. Kidney HGD activity which remained intact reduced urinary HGA, most likely by increased absorption, but did not reduce plasma HGA nor did it prevent ochronosis. In addition, downstream metabolites of exogenous 13C6-HGA, were detected in heterozygous plasma, revealing that hepatocytes take up and metabolise HGA. This novel alkaptonuria mouse model demonstrated the importance of targeting liver for therapeutic intervention, supported by our observation that hepatocytes take up and metabolise HGA

CD33 Alzheimer’s disease locus: Altered monocyte function and amyloid biology

In our functional dissection of the CD33 Alzheimer’s disease susceptibility locus, we find that the rs3865444C risk allele is associated with greater cell surface expression of CD33 in monocytes (t50 = 10.06, pjoint=1.3×10–13) of young and older individuals. It is also associated with (1) diminished internalization of Aβ42) (2) accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging and (3), increased numbers of activated human microglia

Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity.

Study objectives: Patients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample. Methods: 1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates. Results: Patients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009). Conclusions: Time-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients. Clinical trial information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966. Keywords: autonomic nervous activity; frequency domain analysis; heart rate variability; nonlinear dynamic analysis; obstructive sleep apnea; time domain analysis; wakefulness.Peer reviewe