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Article ; Online: The Gompertz Law emerges naturally from the inter-dependencies between sub-components in complex organisms

Pernille Yde Nielsen / Majken K Jensen / Namiko Mitarai / Samir Bhatt

Scientific Reports, Vol 14, Iss 1, Pp 1-

2024 Volume 11

Abstract: Abstract Understanding and facilitating healthy aging has become a major goal in medical research and it is becoming increasingly acknowledged that there is a need for understanding the aging phenotype as a whole rather than focusing on individual ... ...

Abstract	Abstract Understanding and facilitating healthy aging has become a major goal in medical research and it is becoming increasingly acknowledged that there is a need for understanding the aging phenotype as a whole rather than focusing on individual factors. Here, we provide a universal explanation for the emergence of Gompertzian mortality patterns using a systems approach to describe aging in complex organisms that consist of many inter-dependent subsystems. Our model relates to the Sufficient-Component Cause Model, widely used within the field of epidemiology, and we show that including inter-dependencies between subsystems and modeling the temporal evolution of subsystem failure results in Gompertizan mortality on the population level. Our model also provides temporal trajectories of mortality-risk for the individual. These results may give insight into understanding how biological age evolves stochastically within the individual, and how this in turn leads to a natural heterogeneity of biological age in a population.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pyfectious

Arash Mehrjou / Ashkan Soleymani / Amin Abyaneh / Samir Bhatt / Bernhard Schölkopf / Stefan Bauer

PLoS Computational Biology, Vol 19, Iss 1, p e

An individual-level simulator to discover optimal containment policies for epidemic diseases.

2023 Volume 1010799

Abstract: Simulating the spread of infectious diseases in human communities is critical for predicting the trajectory of an epidemic and verifying various policies to control the devastating impacts of the outbreak. Many existing simulators are based on ... ...

Abstract	Simulating the spread of infectious diseases in human communities is critical for predicting the trajectory of an epidemic and verifying various policies to control the devastating impacts of the outbreak. Many existing simulators are based on compartment models that divide people into a few subsets and simulate the dynamics among those subsets using hypothesized differential equations. However, these models lack the requisite granularity to study the effect of intelligent policies that influence every individual in a particular way. In this work, we introduce a simulator software capable of modeling a population structure and controlling the disease's propagation at an individualistic level. In order to estimate the confidence of the conclusions drawn from the simulator, we employ a comprehensive probabilistic approach where the entire population is constructed as a hierarchical random variable. This approach makes the inferred conclusions more robust against sampling artifacts and gives confidence bounds for decisions based on the simulation results. To showcase potential applications, the simulator parameters are set based on the formal statistics of the COVID-19 pandemic, and the outcome of a wide range of control measures is investigated. Furthermore, the simulator is used as the environment of a reinforcement learning problem to find the optimal policies to control the pandemic. The obtained experimental results indicate the simulator's adaptability and capacity in making sound predictions and a successful policy derivation example based on real-world data. As an exemplary application, our results show that the proposed policy discovery method can lead to control measures that produce significantly fewer infected individuals in the population and protect the health system against saturation.
Keywords	Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sex differences in health care expenditures and mortality after spousal bereavement

Alexandros Katsiferis / Samir Bhatt / Laust Hvas Mortensen / Swapnil Mishra / Rudi G J Westendorp

PLoS ONE, Vol 18, Iss 3, p e

A register-based Danish cohort study.

2023 Volume 0282892

Abstract: Background Spousal bereavement is a life event that affects older people differently. We investigated the impact of spousal bereavement on medical expenditures and mortality in the general population, emphasizing on age and sex. Methods Data are from a ... ...

Abstract	Background Spousal bereavement is a life event that affects older people differently. We investigated the impact of spousal bereavement on medical expenditures and mortality in the general population, emphasizing on age and sex. Methods Data are from a population-based, retrospective cohort study following 924,958 Danish citizens over the age of 65 years, within 2011-2016. Changes in health care expenditures in those who suffer bereavement were compared with time matched changes among those who did not. Mortality hazards were analysed with time to event analysis. Results A total of 77,722 (~8.4%) individuals experienced bereavement, 65.8% being females. Among males, bereavement was associated with increase of expenditures the year after, that was 42 Euros per week (95% CI, 36 to 48) larger than the non-bereaved group. The corresponding increase for females was 35 Euros per week (95% CI, 30 to 40). The increase of mortality hazards was highest in the first year after bereavement, higher in males than females, in young old and almost absent in the oldest old. Compared with the reference, mortality the year after spousal loss was 70% higher (HR 1.70 [95% CI 1.40 to 2.08]) for males aged 65-69 years and remained elevated for a period of six years. Mortality for females aged 65-69 years was 27% higher in the first year (HR 1.27, [1.07 to 1.52]), normalizing thereafter. Conclusion Bereavement affects older people differently with younger males being most frail with limited recovery potential.
Keywords	Medicine ; R ; Science ; Q
Subject code	590
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Inference of malaria reproduction numbers in three elimination settings by combining temporal data and distance metrics

Isobel Routledge / H. Juliette T. Unwin / Samir Bhatt

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 21

Abstract: Abstract Individual-level geographic information about malaria cases, such as the GPS coordinates of residence or health facility, is often collected as part of surveillance in near-elimination settings, but could be more effectively utilised to infer ... ...

Abstract	Abstract Individual-level geographic information about malaria cases, such as the GPS coordinates of residence or health facility, is often collected as part of surveillance in near-elimination settings, but could be more effectively utilised to infer transmission dynamics, in conjunction with additional information such as symptom onset time and genetic distance. However, in the absence of data about the flow of parasites between populations, the spatial scale of malaria transmission is often not clear. As a result, it is important to understand the impact of varying assumptions about the spatial scale of transmission on key metrics of malaria transmission, such as reproduction numbers. We developed a method which allows the flexible integration of distance metrics (such as Euclidian distance, genetic distance or accessibility matrices) with temporal information into a single inference framework to infer malaria reproduction numbers. Twelve scenarios were defined, representing different assumptions about the likelihood of transmission occurring over different geographic distances and likelihood of missing infections (as well as high and low amounts of uncertainty in this estimate). These scenarios were applied to four individual level datasets from malaria eliminating contexts to estimate individual reproduction numbers and how they varied over space and time. Model comparison suggested that including spatial information improved models as measured by second order AIC (ΔAICc), compared to time only results. Across scenarios and across datasets, including spatial information tended to increase the seasonality of temporal patterns in reproduction numbers and reduced noise in the temporal distribution of reproduction numbers. The best performing parameterisations assumed long-range transmission (> 200 km) was possible. Our approach is flexible and provides the potential to incorporate other sources of information which can be converted into distance or adjacency matrices such as travel times or molecular ...
Keywords	Medicine ; R ; Science ; Q
Subject code	550
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cancer burden among adolescents and young adults in relation to childhood adversity

Naja Hulvej Rod / Jessica Bengtsson / Leonie K. Elsenburg / Megan Davies / David Taylor-Robinson / Samir Bhatt / Andreas Rieckmann

The Lancet Regional Health. Europe, Vol 27, Iss , Pp 100588- (2023)

a nationwide life-course cohort study of 1.2 million individualsResearch in context

2023

Abstract: Summary: Background: Childhood adversity such as poverty, loss of a parent, and dysfunctional family dynamics may be associated with exposure to environmental and behavioral hazards, interfere with normal biological functions, and affect cancer care and ... ...

Abstract	Summary: Background: Childhood adversity such as poverty, loss of a parent, and dysfunctional family dynamics may be associated with exposure to environmental and behavioral hazards, interfere with normal biological functions, and affect cancer care and outcomes. To explore this hypothesis, we assessed the cancer burden among young men and women exposed to adversity during childhood. Methods: We undertook a population-based study using Danish nationwide register data on childhood adversity and cancer outcomes. Children who were alive and resident in Denmark until their 16th birthday were followed into young adulthood (16–38 years). Group-based multi-trajectory modelling was used to categorize individuals into five distinct groups: low adversity, early material deprivation, persistent material deprivation, loss/threat of loss, and high adversity. We assessed the association with overall cancer incidence, mortality, and five-year case fatality; and cancer specific outcomes for the four most common cancers in this age group in sex-stratified survival analyses. Findings: 1,281,334 individuals born between Jan 1, 1980, and Dec 31, 2001, were followed up until Dec 31, 2018, capturing 8229 incident cancer cases and 662 cancer deaths. Compared to low adversity, women who experienced persistent material deprivation carried a slightly lower risk of overall cancer (hazard ratio (HR) 0.90; 95% CI 0.82; 0.99), particularly due to malignant melanoma and brain and central nervous system cancers, while women who experienced high adversity carried a higher risk of breast cancer (HR 1.71; 95% CI 1.09; 2.70) and cervical cancer incidence (HR 1.82; 95% CI 1.18; 2.83). While there was no clear association between childhood adversity and cancer incidence in men, those men who had experienced persistent material deprivation (HR 1.72; 95% CI 1.29; 2.31) or high adversity (HR 2.27; 95% CI 1.38; 3.72) carried a disproportionate burden of cancer mortality during adolescence or young adulthood compared to men in the low adversity group. ...
Keywords	Childhood adversity ; Cancer incidence ; Cancer mortality ; Cancer case fatality ; Health inequality ; Public aspects of medicine ; RA1-1270
Subject code	610 ; 360
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Danish Pathology Life Course (PATHOLIFE) cohort

Laust Hvas Mortensen / Samir Bhatt / Majken Karoline Jensen / Pernille Yde Nielsen / Andreas Bartholdy / Lise Mette Rahbek Gjerdrum / Rudi Gerardus Johannes Westendorp

BMJ Open, Vol 13, Iss

a register based cohort extending upon a national tissue biobank

2023 Volume 4

Abstract: Purpose The Danish Pathology Life Course (PATHOLIFE) cohort was established to facilitate epidemiological research relating histological and cytological features extracted from patient tissue specimens to the rich life course histories, including both ... ...

Abstract	Purpose The Danish Pathology Life Course (PATHOLIFE) cohort was established to facilitate epidemiological research relating histological and cytological features extracted from patient tissue specimens to the rich life course histories, including both prior and future register data, of the entire Danish population. Research results may increase quality of diagnosis, prognosis and stratification of patient subtypes, possibly identifying novel routes of treatment.Participants All Danish residents from 1 January 1986 to 31 December 2019, totalling 8 593 421 individuals.Findings to date We provide an overview of the subpopulation of Danish residents who have had a tissue specimen investigated within the Danish healthcare system, including both the primary sector and hospitals. We demonstrate heterogeneity in sociodemographic and prognostic factors between the general Danish population and the above mentioned subpopulation, and also between the general Danish population and subpopulations of patients with tissue specimens from selected anatomical sites. Results demonstrate the potential of the PATHOLIFE cohort for integrating many different factors into identification and selection of the most valuable tissue blocks for studies of specific diseases and their progression. Broadly, we find that living with a partner, having higher education and income associates with having a biopsy overall. However, this association varies across different tissue and patient types, which also display differences in time-to-death and causes of death.Future plans The PATHOLIFE cohort may be used to study specified patient groups and link health related events from several national health registries, and to sample patient groups, for which stored tissue specimens are available for further research investigations. The PATHOLIFE cohort thereby provides a unique opportunity to prospectively follow people that were characterised and sampled in the past.
Keywords	Medicine ; R
Subject code	300
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: No evidence of sustained nonzoonotic Plasmodium knowlesi transmission in Malaysia from modelling malaria case data

Kimberly M. Fornace / Hillary M. Topazian / Isobel Routledge / Syafie Asyraf / Jenarun Jelip / Kim A. Lindblade / Mohammad Saffree Jeffree / Pablo Ruiz Cuenca / Samir Bhatt / Kamruddin Ahmed / Azra C. Ghani / Chris Drakeley

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 8

Abstract: Abstract Reported incidence of the zoonotic malaria Plasmodium knowlesi has markedly increased across Southeast Asia and threatens malaria elimination. Nonzoonotic transmission of P. knowlesi has been experimentally demonstrated, but it remains unknown ... ...

Abstract	Abstract Reported incidence of the zoonotic malaria Plasmodium knowlesi has markedly increased across Southeast Asia and threatens malaria elimination. Nonzoonotic transmission of P. knowlesi has been experimentally demonstrated, but it remains unknown whether nonzoonotic transmission is contributing to increases in P. knowlesi cases. Here, we adapt model-based inference methods to estimate R C , individual case reproductive numbers, for P. knowlesi, P. falciparum and P. vivax human cases in Malaysia from 2012–2020 (n = 32,635). Best fitting models for P. knowlesi showed subcritical transmission (R C < 1) consistent with a large reservoir of unobserved infection sources, indicating P. knowlesi remains a primarily zoonotic infection. In contrast, sustained transmission (R C > 1) was estimated historically for P. falciparum and P. vivax, with declines in R C estimates observed over time consistent with local elimination. Together, this suggests sustained nonzoonotic P. knowlesi transmission is highly unlikely and that new approaches are urgently needed to control spillover risks.
Keywords	Science ; Q
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

Pantelis Samartsidis / Seth Flaxman / Samir Bhatt / Daniel J Laydon / Swapnil Mishra / Wes R Hinsley / Axel Gandy / Neil M Ferguson

BMJ Open, Vol 11, Iss

Early life socioeconomic position and mortality from cardiovascular diseases: an application of causal mediation analysis in the Stockholm Public Health Cohort

2021 Volume 4

Keywords	Medicine ; R
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modelling the impact of the tier system on SARS-CoV-2 transmission in the UK between the first and second national lockdowns

Pantelis Samartsidis / Seth Flaxman / Samir Bhatt / Daniel J Laydon / Swapnil Mishra / Wes R Hinsley / Axel Gandy / Neil M Ferguson

BMJ Open, Vol 11, Iss

2021 Volume 4

Abstract: Objective To measure the effects of the tier system on the COVID-19 pandemic in the UK between the first and second national lockdowns, before the emergence of the B.1.1.7 variant of concern.Design This is a modelling study combining estimates of real- ... ...

Abstract	Objective To measure the effects of the tier system on the COVID-19 pandemic in the UK between the first and second national lockdowns, before the emergence of the B.1.1.7 variant of concern.Design This is a modelling study combining estimates of real-time reproduction number Rt (derived from UK case, death and serological survey data) with publicly available data on regional non-pharmaceutical interventions. We fit a Bayesian hierarchical model with latent factors using these quantities to account for broader national trends in addition to subnational effects from tiers.Setting The UK at lower tier local authority (LTLA) level. 310 LTLAs were included in the analysis.Primary and secondary outcome measures Reduction in real-time reproduction number Rt.Results Nationally, transmission increased between July and late September, regional differences notwithstanding. Immediately prior to the introduction of the tier system, Rt averaged 1.3 (0.9–1.6) across LTLAs, but declined to an average of 1.1 (0.86–1.42) 2 weeks later. Decline in transmission was not solely attributable to tiers. Tier 1 had negligible effects. Tiers 2 and 3, respectively, reduced transmission by 6% (5%–7%) and 23% (21%–25%). 288 LTLAs (93%) would have begun to suppress their epidemics if every LTLA had gone into tier 3 by the second national lockdown, whereas only 90 (29%) did so in reality.Conclusions The relatively small effect sizes found in this analysis demonstrate that interventions at least as stringent as tier 3 are required to suppress transmission, especially considering more transmissible variants, at least until effective vaccination is widespread or much greater population immunity has amassed.
Keywords	Medicine ; R
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Faster Adaptation in Smaller Populations

Jayna Raghwani / Samir Bhatt / Oliver G Pybus

PLoS Computational Biology, Vol 12, Iss 1, p e

Counterintuitive Evolution of HIV during Childhood Infection.

2016 Volume 1004694

Abstract: Analysis of HIV-1 gene sequences sampled longitudinally from infected individuals can reveal the evolutionary dynamics that underlie associations between disease outcome and viral genetic diversity and divergence. Here we extend a statistical framework ... ...

Abstract	Analysis of HIV-1 gene sequences sampled longitudinally from infected individuals can reveal the evolutionary dynamics that underlie associations between disease outcome and viral genetic diversity and divergence. Here we extend a statistical framework to estimate rates of viral molecular adaptation by considering sampling error when computing nucleotide site-frequencies. This is particularly beneficial when analyzing viral sequences from within-host viral infections if the number of sequences per time point is limited. To demonstrate the utility of this approach, we apply our method to a cohort of 24 patients infected with HIV-1 at birth. Our approach finds that viral adaptation arising from recurrent positive natural selection is associated with the rate of HIV-1 disease progression, in contrast to previous analyses of these data that found no significant association. Most surprisingly, we discover a strong negative correlation between viral population size and the rate of viral adaptation, the opposite of that predicted by standard molecular evolutionary theory. We argue that this observation is most likely due to the existence of a confounding third variable, namely variation in selective pressure among hosts. A conceptual non-linear model of virus adaptation that incorporates the two opposing effects of host immunity on the virus population can explain this counterintuitive result.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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