Shortest Reconfiguration of Matchings

Imagine that unlabelled tokens are placed on the edges of a graph, such that no two tokens are placed on incident edges. A token can jump to another edge if the edges having tokens remain independent. We study the problem of determining the distance between two token configurations (resp., the corresponding matchings), which is given by the length of a shortest transformation. We give a polynomial-time algorithm for the case that at least one of the two configurations is not inclusion-wise maximal and show that otherwise, the problem admits no polynomial-time sublogarithmic-factor approximation unless P = NP. Furthermore, we show that the distance of two configurations in bipartite graphs is fixed-parameter tractable parameterized by the size $d$ of the symmetric difference of the source and target configurations, and obtain a $d^\varepsilon$-factor approximation algorithm for every $\varepsilon > 0$ if additionally the configurations correspond to maximum matchings. Our two main technical tools are the Edmonds-Gallai decomposition and a close relation to the Directed Steiner Tree problem. Using the former, we also characterize those graphs whose corresponding configuration graphs are connected. Finally, we show that deciding if the distance between two configurations is equal to a given number $\ell$ is complete for the class $D^P$, and deciding if the diameter of the graph of configurations is equal to $\ell$ is $D^P$-hard.Comment: 31 pages, 3 figure

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

The reuse of digital computer data: Transformation, recombination and generation of data mixes in big data science

This is the author accepted manuscript. the final version is available on open access from Springer via the DOI in this recordThis chapter is concerned with the relationship between the materiality of digital computer data and their reuse in scientific practice. It builds on the case study of a ‘data mash-up’ infrastructure for research with environmental, weather and population health data. I problematise the extent to which scientists reusing digital computer data heavily manipulate the sources through complex and situated calculative operations, as they attempt to re-situate data well beyond the epistemic community in which they originated, and adapt them to different theoretical frameworks, methods and evidential standards. The chapter interrogates the consequent relationship between derivative data and the data sources from which they originate. The deep relationality of scientific computer data is multi-layered and scaffolded, as it depends on relations between various kinds of data, computing technologies, assumptions, theoretical scaffoldings, hypotheses and other features of the situation at hand.European Research Council (ERC)Engineering and Physical Sciences Research Council (EPSRC

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers