Mobile phones as medical devices in mental disorder treatment: an overview

Mental disorders can have a significant, negative impact on sufferers’ lives, as well as on their friends and family, healthcare systems and other parts of society. Approximately 25 % of all people in Europe and the USA experience a mental disorder at least once in their lifetime. Currently, monitoring mental disorders relies on subjective clinical self-reporting rating scales, which were developed more than 50 years ago. In this paper, we discuss how mobile phones can support the treatment of mental disorders by (1) implementing human–computer interfaces to support therapy and (2) collecting relevant data from patients’ daily lives to monitor the current state and development of their mental disorders. Concerning the first point, we review various systems that utilize mobile phones for the treatment of mental disorders. We also evaluate how their core design features and dimensions can be applied in other, similar systems. Concerning the second point, we highlight the feasibility of using mobile phones to collect comprehensive data including voice data, motion and location information. Data mining methods are also reviewed and discussed. Based on the presented studies, we summarize advantages and drawbacks of the most promising mobile phone technologies for detecting mood disorders like depression or bipolar disorder. Finally, we discuss practical implementation details, legal issues and business models for the introduction of mobile phones as medical devices

Investigation of Swedish cases reveals an outbreak of cryptosporidiosis at a Norwegian hotel with possible links to in-house water systems

<p>Abstract</p> <p>Background</p> <p>In March 2007, the Norwegian Institute of Public Health was notified of Swedish individuals diagnosed with cryptosporidiosis after staying at a Norwegian hotel. In Norway, cryptosporidiosis is not reportable, and human infections are rarely diagnosed.</p> <p>Methods</p> <p>A questionnaire on illness and exposure history was e-mailed to seven organised groups who had visited the hotel in March. Cases were defined as persons with diarrhoea for more than two days or laboratory-confirmed cryptosporidiosis during or within two weeks of the hotel visit. The risk factor analysis was restricted to two groups with the highest attack rates (AR) and same hotel stay period. Local food safety authorities conducted environmental investigations.</p> <p>Results</p> <p>In total, 25 diarrhoeal cases (10 laboratory-confirmed) were identified among 89 respondents. Although environmental samples were negative, epidemiological data suggest an association with in-house water consumption. In one group, the AR was higher amongst consumers of water from hotel dispenser (relative risk [RR] = 3.0; 95% confidence interval [CI]: 0.9–9.8), tap water (RR = 2.3; CI: 0.9–5.8), and lower amongst commercial bottled water drinkers (RR = 0.6; CI: 0.4–1.0). Consumption of ice cubes was a risk-factor (RR = 7.1; CI: 1.1–45.7) in the two groups combined.</p> <p>Conclusion</p> <p>This outbreak would probably have remained undetected without the alert from Swedish health authorities, illustrating the difficulties in outbreak detection due to low health care seeking behaviour for diarrhoea and limited parasite diagnostics in Norway. Awareness of cryptosporidiosis should be raised amongst Norwegian medical personnel to improve case and outbreak detection, and possible risks related to in-house water systems should be assessed.</p

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Analysis of long-term observations of NOx and CO in megacities and application to constraining emissions inventories

Long-term atmospheric NOx/CO enhancement ratios in megacities provide evaluations of emission inventories. A fuel-based emission inventory approach that diverges from conventional bottom-up inventory methods explains 1970–2015 trends in NOx/CO enhancement ratios in Los Angeles. Combining this comparison with similar measurements in other U.S. cities demonstrates that motor vehicle emissions controls were largely responsible for U.S. urban NOx/CO trends in the past half century. Differing NOx/CO enhancement ratio trends in U.S. and European cities over the past 25 years highlights alternative strategies for mitigating transportation emissions, reflecting Europe's increased use of light-duty diesel vehicles and correspondingly slower decreases in NOx emissions compared to the U.S. A global inventory widely used by global chemistry models fails to capture these long-term trends and regional differences in U.S. and Europe megacity NOx/CO enhancement ratios, possibly contributing to these models' inability to accurately reproduce observed long-term changes in tropospheric ozone

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

BACKGROUND : Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS : We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS : Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94–1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85–1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06–1.48) and HR = 1.59 (95% CI: 1.08–2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCUSION : Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.https://www.nature.com/bjc2020-06-19hj2020Genetic

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Abstract Introduction Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects

Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4