Families - A Summary of the Situation in Europe Today

Information brochure No. 1 on the state of knowledge on contemporary family life in Europe and key issues for policy and researc

Civil Society Perspective

Three case studies, taken from within the FAMILYPLATFORM consortium, of family organisations operating at the local, national, European, and global levels

175 GHz, 400-fs-pulse harmonically mode-locked surface emitting semiconductor laser

We report a harmonically mode-locked vertical external cavity surface emitting laser (VECSEL) producing 400 fs pulses at a repetition frequency of 175 GHz with an average output power of 300 mW. Harmonic mode-locking was established using a 300 µm thick intracavity single crystal diamond heat spreader in thermal contact with the front surface of the gain sample using liquid capillary bonding. The repetition frequency was set by the diamond microcavity and stable harmonic mode locking was achieved when the laser cavity length was tuned so that the laser operated on the 117th harmonic of the fundamental cavity. When an etalon placed intracavity next to the gain sample, but not in thermal contact was used pulse groups were observed. These contained 300 fs pulses with a spacing of 5.9 ps. We conclude that to achieve stable harmonic mode locking at repetition frequencies in the 100s of GHz range in a VECSEL there is a threshold pulse energy above which harmonic mode locking is achieved and below which groups of pulses are observed

Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in LRRK2 p.Gly2019Ser Parkinsonism.

peer reviewed[en] BACKGROUND: A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk. OBJECTIVE: To investigate the impact of the MGS and lifestyle/environment on age at onset (AAO) in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic PD (iPD). METHODS: We included N = 486 patients with LRRK2-PD and N = 9259 with iPD from the Accelerating Medicines Partnership® Parkinson's Disease Knowledge Platform (AMP-PD), Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data were used to perform the MGS analysis. Additionally, lifestyle/environmental data were obtained from the PD Risk Factor Questionnaire (PD-RFQ). Linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO. RESULTS: Our derived MGS was significantly higher in PD cases compared with controls (P = 1.1 × 10-8 ). We observed that higher MGS was significantly associated with earlier AAO in LRRK2-PD (P = 0.047, β = -1.40) and there was the same trend with a smaller effect size in iPD (P = 0.231, β = 0.22). There was a correlation between MGS and AAO in LRRK2-PD patients of European descent (P = 0.049, r = -0.12) that was visibly less pronounced in Tunisians (P = 0.449, r = -0.05). We found that the MGS interacted with caffeinated soda consumption (P = 0.003, β = -5.65) in LRRK2-PD and with tobacco use (P = 0.010, β = 1.32) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeinated soda or were non-smokers. CONCLUSIONS: The MGS was more strongly associated with earlier AAO in LRRK2-PD compared with iPD. Caffeinated soda consumption or tobacco use interacted with MGS to predict AAO. Our study suggests gene-environment interactions as modifiers of AAO in LRRK2-PD

Spotlights on Contemporary Family Life

Spotlights on Contemporary Family Life covers four issues of cross-cutting importance to families Structures and forms of families: issues relating to a diversification of families away from the ‘traditional nuclear family form’ are relatively uncontroversial from an academic perspective, but much more so for policy makers and family associations. Chapter 1 provides a thorough overview of the state of contemporary European families. Solidarities in families: too often the issue of an ‘ageing society’ is simply reduced to the problem of over-burdening social care systems, but longevity also represents opportunities for new kinds of solidarities inside families and family networks, and new relations between family members – not to mention the satisfaction felt by people who can continue to live fulfilling and rewarding lives long after they’re considered ‘elderly’. Chapter 2 gives voice to authors who identify these new opportunities and challenges. Demographic change: women are having fewer children and having them later in life. Having children is now a conscious decision and fertility rates have declined below the level required to sustain our current populations. At the same time we witness the ‘greying’ of Europe, which brings with it a whole host of opportunities and challenges. Chapter 3 raises important issues for policy makers today. Volunteering: inspired by family associations who could not survive without the support of volunteers, this chapter gives an overview of what’s known - and what isn’t - about volunteering. Coinciding with the European Year of Volunteering 2011, this chapter takes a timely look at the efforts that families put into volunteering across Europe and the important benefits that Europe gains from all of this combined voluntary effort. Linden Farrer and William Lay work for the Confederation of Family Organisations in the European Union (COFACE). This publication was produced by FAMILYPLATFORM, a project funded by the European Commission

Spotlights on Contemporary Family Life

Spotlights on Contemporary Family Life covers four issues of cross-cutting importance to families Structures and forms of families: issues relating to a diversification of families away from the ‘traditional nuclear family form’ are relatively uncontroversial from an academic perspective, but much more so for policy makers and family associations. Chapter 1 provides a thorough overview of the state of contemporary European families. Solidarities in families: too often the issue of an ‘ageing society’ is simply reduced to the problem of over-burdening social care systems, but longevity also represents opportunities for new kinds of solidarities inside families and family networks, and new relations between family members – not to mention the satisfaction felt by people who can continue to live fulfilling and rewarding lives long after they’re considered ‘elderly’. Chapter 2 gives voice to authors who identify these new opportunities and challenges. Demographic change: women are having fewer children and having them later in life. Having children is now a conscious decision and fertility rates have declined below the level required to sustain our current populations. At the same time we witness the ‘greying’ of Europe, which brings with it a whole host of opportunities and challenges. Chapter 3 raises important issues for policy makers today. Volunteering: inspired by family associations who could not survive without the support of volunteers, this chapter gives an overview of what’s known - and what isn’t - about volunteering. Coinciding with the European Year of Volunteering 2011, this chapter takes a timely look at the efforts that families put into volunteering across Europe and the important benefits that Europe gains from all of this combined voluntary effort. Linden Farrer and William Lay work for the Confederation of Family Organisations in the European Union (COFACE). This publication was produced by FAMILYPLATFORM, a project funded by the European Commission

Genome-wide association study identifies four novel loci associated with Alzheimer's endophenotypes and disease modifiers

More than 20 genetic loci have been associated with risk for Alzheimer's disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case-control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = -0.059, P = 2.08 × 10-8) and within SERPINB1 on 6p25 (β = -0.025, P = 1.72 × 10-8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10-2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10-2), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10-3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform future AD studies

Mitochondrial DNA heteroplasmy distinguishes disease manifestation in PINK1/PRKN-linked Parkinson’s disease

Biallelic mutations in PINK1/PRKN cause recessive Parkinson’s disease. Given the established role of PINK1/Parkin in regulating mitochondrial dynamics, we explored mitochondrial DNA (mtDNA) integrity and inflammation as disease modifiers in carriers of mutations in these genes. MtDNA integrity was investigated in a large collection of biallelic (n = 84) and monoallelic (n = 170) carriers of PINK1/PRKN mutations, idiopathic Parkinson’s disease patients (n = 67) and controls (n = 90). In addition, we studied global gene expression and serum cytokine levels in a subset. Affected and unaffected PINK1/PRKN monoallelic mutation carriers can be distinguished by heteroplasmic mtDNA variant load (AUC = 0.83, CI:0.74-0.93). Biallelic PINK1/PRKN mutation carriers harbor more heteroplasmic mtDNA variants in blood (p = 0.0006, Z = 3.63) compared to monoallelic mutation carriers. This enrichment was confirmed in iPSC-derived (controls, n = 3; biallelic PRKN mutation carriers, n = 4) and postmortem (control, n = 1; biallelic PRKN mutation carrier, n = 1) midbrain neurons. Lastly, the heteroplasmic mtDNA variant load correlated with IL6 levels in PINK1/PRKN mutation carriers (r = 0.57, p = 0.0074). PINK1/PRKN mutations predispose individuals to mtDNA variant accumulation in a dose- and disease-dependent manner

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease