Search

The pathophysiological mechanisms underlying the seasonal dynamic and epidemic occurrence of bacterial meningitis in the African meningitis belt remain unknown. Regular seasonality (seasonal hyperendemicity) is observed for both meningococcal and pneumococcal meningitis and understanding this is critical for better prevention and modelling. The two principal hypotheses for hyperendemicity during the dry season imply (1) an increased risk of invasive disease given asymptomatic carriage of meningococci and pneumococci; or (2) an increased transmission of these bacteria from carriers and ill individuals. In this study, we formulated three compartmental deterministic models of seasonal hyperendemicity, featuring one (model1-'inv' or model2-'transm'), or a combination (model3-'inv-transm') of the two hypotheses. We parameterised the models based on current knowledge on meningococcal and pneumococcal biology and pathophysiology. We compared the three models' performance in reproducing weekly incidences of suspected cases of acute bacterial meningitis reported by health centres in Burkina Faso during 2004-2010, through the meningitis surveillance system. The three models performed well (coefficient of determination R2, 0.72, 0.86 and 0.87, respectively). Model2-'transm' and model3-'inv-transm' better captured the amplitude of the seasonal incidence. However, model2-'transm' required a higher constant invasion rate for a similar average baseline transmission rate. The results suggest that a combination of seasonal changes of the risk of invasive disease and carriage transmission is involved in the hyperendemic seasonality of bacterial meningitis in the African meningitis belt. Consequently, both interventions reducing the risk of nasopharyngeal invasion and the bacteria transmission, especially during the dry season are believed to be needed to limit the recurrent seasonality of bacterial meningitis in the meningitis belt. [ABSTRACT FROM AUTHOR]

Despite improved surveillance capacities and WHO recommendations for subdistrict analysis, routine epidemic surveillance of acute bacterial meningitis in the African meningitis belt remains largely limited to the district level. We evaluated the appropriateness and performance of analyses at higher spatial resolution. We used suspected meningitis surveillance data at health centre (HC) resolution from Burkina Faso from 14 health districts spanning years 2004-2014 and analysed them using spatio-temporal statistics and generative models. An operational analysis compared epidemic signals at district and HC-level using weekly incidence thresholds. Eighty-four percent (N = 98/116) of epidemic clusters spanned only one HC-week. Spatial propagation of epidemic clusters was mostly limited to 10-30 km. During the 2004-2009 (with serogroup A meningitis) and 2010-2014 (after serogroup A elimination) period, using weekly HC-level incidence thresholds of 100 and 50 per 100,000 respectively, we found a gain in epidemic detection and timeliness in 9 (41% of total) and 10 (67%), respectively, district years with at least one HC signal. Individual meningitis epidemics expanded little in space, suggesting that a health centre level analysis is most appropriate for epidemic surveillance. Epidemic surveillance could gain in precision and timeliness by higher spatial resolution. The optimal threshold should be defined depending on the current background incidence of bacterial meningitis., (© 2022. The Author(s).)

Our understanding of the physical principles organizing the genome in the nucleus is limited by the lack of tools to directly exert and measure forces on interphase chromosomes in vivo and probe their material nature. Here, we introduce an approach to actively manipulate a genomic locus using controlled magnetic forces inside the nucleus of a living human cell. We observed viscoelastic displacements over micrometers within minutes in response to near-piconewton forces, which are consistent with a Rouse polymer model. Our results highlight the fluidity of chromatin, with a moderate contribution of the surrounding material, revealing minor roles for cross-links and topological effects and challenging the view that interphase chromatin is a gel-like material. Our technology opens avenues for future research in areas from chromosome mechanics to genome functions.

Background: Global trends in cardiovascular disease (CVD) exhibit considerable interregional and interethnic differences, which in turn affect long-term CVD risk across diverse populations. An in-depth understanding of the interplay between ethnicity, socioeconomic status, and CVD risk factors and mortality in a contemporaneous population is crucial to informing health policy and resource allocation aimed at mitigating long-term CVD risk. Generating bespoke large-scale and reliable data with sufficient numbers of events is expensive and time-consuming but can be circumvented through utilization and linkage of data routinely collected in electronic health records (EHR)., Objective: We aimed to characterize the burden of CVD risk factors across different ethnicities, age groups, and socioeconomic groups, and study CVD incidence and mortality by EHR linkage in London., Methods: The proposed study will initially be a cross-sectional observational study unfolding into prospective CVD ascertainment through longitudinal follow-up involving linked data. The government-funded National Health System (NHS) Health Check program provides an opportunity for the systematic collation of CVD risk factors on a large scale. NHS Health Check data on approximately 200,000 individuals will be extracted from consenting general practices across London that use the Egton Medical Information Systems (EMIS) EHR software. Data will be analyzed using appropriate statistical techniques to (1) determine the cross-sectional burden of CVD risk factors and their prospective association with CVD outcomes, (2) validate existing prediction tools in diverse populations, and (3) develop bespoke risk prediction tools across diverse ethnic groups., Results: Enrollment began in January 2019 and is ongoing with initial results to be published mid-2021., Conclusions: There is an urgent need for more real-life population health studies based on analyses of routine health data available in EHRs. Findings from our study will help quantify, on a large scale, the contemporaneous burden of CVD risk factors by geography and ethnicity in a large multiethnic urban population. Such detailed understanding (especially interethnic and sociodemographic variations) of the burden of CVD risk and its determinants, including heredity, environment, diet, lifestyle, and socioeconomic factors, in a large population sample, will enable the development of tailored and dynamic (continuously learning from new data) risk prediction tools for diverse ethnic groups, and thereby enable the personalized provision of prevention strategies and care. We anticipate that this systematic approach of linking routinely collected data from EHRs to study CVD can be conducted in other settings as EHRs are being implemented worldwide., International Registered Report Identifier (irrid): PRR1-10.2196/17548., (©Kanika Dharmayat, Maria Woringer, Nikolaos Mastellos, Della Cole, Josip Car, Sumantra Ray, Kamlesh Khunti, Azeem Majeed, Kausik K Ray, Sreenivasa Rao Kondapally Seshasai. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 02.10.2020.)

Theoretical and experimental observations that catalysis enhances the diffusion of enzymes have generated exciting implications about nanoscale energy flow, molecular chemotaxis, and self-powered nanomachines. However, contradictory claims on the origin, magnitude, and consequence of this phenomenon continue to arise. To date, experimental observations of catalysis-enhanced enzyme diffusion have relied almost exclusively on fluorescence correlation spectroscopy (FCS), a technique that provides only indirect, ensemble-averaged measurements of diffusion behavior. Here, using an anti-Brownian electrokinetic (ABEL) trap and in-solution single-particle tracking, we show that catalysis does not increase the diffusion of alkaline phosphatase (ALP) at the single-molecule level, in sharp contrast to the ∼20% enhancement seen in parallel FCS experiments using p -nitrophenyl phosphate ( p NPP) as substrate. Combining comprehensive FCS controls, ABEL trap, surface-based single-molecule fluorescence, and Monte Carlo simulations, we establish that p NPP-induced dye blinking at the ∼10-ms timescale is responsible for the apparent diffusion enhancement seen in FCS. Our observations urge a crucial revisit of various experimental findings and theoretical models--including those of our own--in the field, and indicate that in-solution single-particle tracking and ABEL trap are more reliable means to investigate diffusion phenomena at the nanoscale., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

The genetic information that instructs transcription and other cellular functions is carried by the chromosomes, polymers of DNA in complex with histones and other proteins. These polymers are folded inside nuclei five orders of magnitude smaller than their linear length, and many facets of this folding correlate with or are causally related to transcription and other cellular functions. Recent advances in sequencing and imaging-based techniques have enabled new views into several layers of chromatin organization. These experimental findings are accompanied by computational modeling efforts based on polymer physics that can provide mechanistic insights and quantitative predictions. Here, we review current knowledge of the main levels of chromatin organization, from the scale of nucleosomes to the entire nucleus, our current understanding of their underlying biophysical and molecular mechanisms, and some of their functional implications.

Background: Frail individuals are at risk of significant clinical deterioration if their frailty is not identified and managed appropriately. Research suggests that any interaction between an older person and a health or social care professional should include an assessment for frailty. Many older care home residents are frail when admitted, but we have little knowledge of whether or how this is assessed. The aim of this paper is to understand and establish the characteristics of the reported 'assessments for frailty' used in care homes with nursing (nursing homes) across North-West London. This will help understand what an 'assessment for frailty' of care home residents mean in practice in North-West London., Methods: Telephone contact was made with every Care Quality Commission (CQC) (independent regulator of health and adult social care in England) regulated nursing home across North-West London [n = 87]. An online survey was sent to all that expressed interest [n = 73]. The survey was developed through conversations with healthcare professionals, based on literature and tested with academics and clinicians. Survey responses were analysed using descriptive statistics. The Mann-Whitney U test was used for statistical analyses., Results: 24/73 nursing homes completed the survey (33%). Differences in the characteristics of reported 'assessments for frailty' across nursing homes were evident. Variation in high level domains assessed (physical, social, mental and environmental) was observed. Nurses were the most common professional group completing assessments for frailty, with documentation and storage being predominantly paper based. A statistically significant difference between the number of assessments used in corporate chain owned nursing homes (3.9) versus independently owned nursing homes (2.1) was observed (U = 21, p = .005)., Conclusions: Great variation existed in the characteristics of reported 'assessments for frailty' in nursing homes. Our study suggests that not all physical, social, mental and environmental domains of frailty are routinely assessed: it appears that frailty is still primarily viewed only in terms of physical health. The consequences of this could be severe for patients, staff and healthcare settings. Research illustrates that frailty is a broad, multifactorial health state and, as such, an overall 'assessment for frailty' should reflect this.

Background: Adoption of healthy lifestyle and compliance with cholesterol-lowering medication reduces the risk of cardiovascular disease (CVD). The use of digital tools and mobile technology may be important for sustaining positive behavioral change., Objective: The primary objective of this study is to evaluate the feasibility and acceptability of administering the Cholesterol CarePlan Web app developed by the American Heart Association aimed at improving lifestyle and medication adherence among patients prescribed cholesterol-lowering medication. The secondary objective is to assess the Web app's efficacy., Methods: A prospective, observational feasibility study will be conducted to demonstrate whether the Web app may be successfully taken up by patients and will be associated with improved clinical and behavioral outcomes. The study will aim to recruit 180 study participants being prescribed cholesterol-lowering medication for at least 30 days across 14 general practices in London, England. Potentially eligible patients will be invited to use the Web app on a smartphone and visit general practice for three 20-minute clinical assessments of blood pressure, height, weight, smoking, and nonfasting cholesterol over 24 weeks. The feasibility of administering the Web app will be judged by recruitment and dropout statistics and the sociodemographic and comorbidity profile of consenting study participants, consenting nonparticipants, and all potentially eligible patients. Acceptability will be assessed using patients' readiness to embrace new technologies, the usability of the Web app, and patient satisfaction. The efficacy of the Web app will be assessed by changes in medication adherence and clinical risk factors by levels of the Web app compliance., Results: This study is currently funded by the American Heart Association. Initial study recruitment will take place between February and July 2018 followed by patient follow-up. Patient level data will be obtained in January 2019. Data analysis will be completed by February 2019. Results will be submitted for publication in March 2019., Conclusions: The potential of an app to improve patients' lifestyle and management of cholesterol may inform the design of a randomized controlled trial and the delivery of more effective CVD prevention programs., International Registered Report Identifier (irrid): PRR1-10.2196/9017., (©Maria Woringer, Kanika I Dharmayat, Geva Greenfield, Alex Bottle, Kausik K Ray. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 24.01.2019.)

Background: Bacterial meningitis causes a high burden of disease in the African meningitis belt, with regular seasonal hyperendemicity and sporadic short, but intense, localized epidemics during the late dry season occurring at a small spatial scale [i.e., below the district level, in individual health centers (HCs)]. In addition, epidemic waves with larger geographic extent occur every 7-10 y. Although atmospheric dust load is thought to be an essential factor for hyperendemicity, its role for localized epidemics remains hypothetic., Objectives: Our goal was to evaluate the association of localized meningitis epidemics in HC catchment areas with the dust load and the occurrence of cases in the same population early in the dry season., Methods: We compiled weekly reported cases of suspected bacterial meningitis at the HC resolution for 14 districts of Burkina Faso for the period 2004-2014. Using logistic regression, we evaluated the association of epidemic HC-weeks with atmospheric dust [approximated by the aerosol optical thickness (AOT) satellite product] and with the observation of early meningitis cases during October-December., Results: Although AOT was strongly associated with epidemic HC-weeks in crude analyses across all HC-weeks during the meningitis season [odds ratio (OR) [Formula: see text]; 95% CI: 4.90, 9.50], the association was no longer apparent when controlling for calendar week (OR [Formula: see text]; 95% CI: 0.60, 1.50). The number of early meningitis cases reported during October-December was associated with epidemic HC-weeks in the same HC catchment area during January-May of the following year (OR for each additional early case [Formula: see text]; 95% CI: 1.06, 1.21)., Conclusions: Spatial variations of atmospheric dust load do not seem to be a factor in the occurrence of localized meningitis epidemics, and the factor triggering them remains to be identified. The pathophysiological mechanism linking early cases to localized epidemics is not understood, but their occurrence and number of early cases could be an indicator for epidemic risk. https://doi.org/10.1289/EHP2752.

Understanding how transcription factors (TFs) regulate mammalian gene expression in space and time is a central topic in biology. To activate a gene, a TF has first to diffuse in the available space of the nucleus until it reaches a target DNA sequence or protein (target site). This eventually results in the recruitment of the whole transcriptional machinery. All these processes take place in the mammalian nucleoplasm, a highly organized and dynamic environment, in which some complexes transiently assemble and break apart, whereas others appear more stable. This diversity of dynamic behaviors arises from the number of biomolecules that make up the nucleoplasm and their pairwise interactions. Indeed, interactions energies that span several orders of magnitude, from covalent bounds to transient and dynamic interactions, can shape nuclear landscapes. Thus, the nuclear environment determines how frequently and how fast a TF contacts its target site, and it indirectly regulates gene expression. How exactly transient interactions are involved in the regulation of TF diffusion is unclear, but are reflected by live cell imaging techniques, including single-particle tracking (SPT). Overall, the macroscopic result of these microscopic interactions is almost always anomalous diffusion, a phenomenon widely studied and modeled. Here, we review the connections between the anomalous diffusion of a TF observed by SPT and the microscopic organization of the nucleus, including recently described topologically associated domains and dynamic phase-separated compartments. We propose that anomalous diffusion found in SPT data result from weak and transient interactions with dynamic nuclear substructures, and that SPT data analysis would benefit from a better description of such structures., (© 2018 The Author(s).)

Single-particle tracking (SPT) has become an important method to bridge biochemistry and cell biology since it allows direct observation of protein binding and diffusion dynamics in live cells. However, accurately inferring information from SPT studies is challenging due to biases in both data analysis and experimental design. To address analysis bias, we introduce 'Spot-On', an intuitive web-interface. Spot-On implements a kinetic modeling framework that accounts for known biases, including molecules moving out-of-focus, and robustly infers diffusion constants and subpopulations from pooled single-molecule trajectories. To minimize inherent experimental biases, we implement and validate stroboscopic photo-activation SPT (spaSPT), which minimizes motion-blur bias and tracking errors. We validate Spot-On using experimentally realistic simulations and show that Spot-On outperforms other methods. We then apply Spot-On to spaSPT data from live mammalian cells spanning a wide range of nuclear dynamics and demonstrate that Spot-On consistently and robustly infers subpopulation fractions and diffusion constants., Competing Interests: AH, MW, XD No competing interests declared, JG has filed patent applications (e.g. PCT/US2015/023953) whose value may be affected by this publication, LL Luke D Lavis: has filed patent applications (e.g. PCT/US2015/023953) whose value may be affected by this publication, RT One of the three founding funders of eLife and a member of eLife's Board of Directors, (© 2018, Hansen et al.)

Background: The National Health Service (NHS) Health Check is a cardiovascular disease (CVD) risk assessment and management programme in England aiming to increase CVD risk awareness among people at increased risk of CVD. There is no tool to assess the effectiveness of the programme in communicating CVD risk to patients., Aims: The aim of this paper was to develop a questionnaire examining patients' CVD risk awareness for use in health service research evaluations of the NHS Health Check programme., Methods: We developed an 85-item questionnaire to determine patients' views of their risk of CVD. The questionnaire was based on a review of the relevant literature. After review by an expert panel and focus group discussion, 22 items were dropped and 2 new items were added. The resulting 65-item questionnaire with satisfactory content validity (content validity indices≥0.80) and face validity was tested on 110 NHS Health Check attendees in primary care in a cross-sectional study between 21 May 2014 and 28 July 2014., Results: Following analyses of data, we reduced the questionnaire from 65 to 26 items. The 26-item questionnaire constitutes four scales: Knowledge of CVD Risk and Prevention, Perceived Risk of Heart Attack/Stroke, Perceived Benefits and Intention to Change Behaviour and Healthy Eating Intentions. Perceived Risk (Cronbach's α=0.85) and Perceived Benefits and Intention to Change Behaviour (Cronbach's α=0.82) have satisfactory reliability (Cronbach's α≥0.70). Healthy Eating Intentions (Cronbach's α=0.56) is below minimum threshold for reliability but acceptable for a three-item scale., Conclusions: The resulting questionnaire, with satisfactory reliability and validity, may be used in assessing patients' awareness of CVD risk among NHS Health Check attendees., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Meningococcal meningitis epidemics in the African meningitis belt consist of localised meningitis epidemics (LME) that reach attack proportions of 1% within a few weeks. A meningococcal serogroup A conjugate vaccine was introduced in meningitis belt countries from 2010 on, but LME due to other serogroups continue to occur. The mechanisms underlying LME are poorly understood, but an association with respiratory pathogens has been hypothesised. We analysed national routine surveillance data in high spatial resolution (health centre level) from 13 districts in Burkina Faso, 2004-2014. We defined LME as a weekly incidence rate of suspected meningitis ≥75 per 100,000 during ≥2 weeks; and high incidence episodes of respiratory tract infections (RTI) as the 5 th quintile of monthly incidences. We included 10,334 health centre month observations during the meningitis season (January-May), including 85 with LME, and 1891 (1820) high-incidence episodes of upper (lower) RTI. In mixed effects logistic regression accounting for spatial structure, and controlling for dust conditions, relative air humidity and month, the occurrence of LME was strongly associated with high incidence episodes of upper (odds ratio 23.9, 95%-confidence interval 3.1-185.3), but not lower RTI. In the African meningitis belt, meningitis epidemics may be triggered by outbreaks of upper RTI.

Objective: To determine if use of point of care testing (POCT) is less costly than laboratory testing to the National Health Service (NHS) in delivering the NHS Health Check (NHSHC) programme in the primary care setting., Design: Observational study and theoretical mathematical model with microcosting approach., Setting: We collected data on NHSHC delivered at nine general practices (seven using POCT; two not using POCT)., Participants: We recruited nine general practices offering NHSHC and a pathology services laboratory in the same area., Methods: We conducted mathematical modelling with permutations in the following fields: provider type (healthcare assistant or nurse), type of test performed (total cholesterol with either lab fasting glucose or HbA1c), cost of consumables and variable uptake rates, including rate of non-response to invite letter and rate of missed [did not attend (DNA)] appointments. We calculated total expected cost (TEC) per 100 invites, number of NHSHC conducted per 100 invites and costs for completed NHSHC for laboratory and POCT-based pathways. A univariate and probabilistic sensitivity analysis was conducted to account for uncertainty in the input parameters., Main Outcome Measures: We collected data on cost, volume and type of pathology services performed at seven general practices using POCT and a pathology services laboratory. We collected data on response to the NHSHC invitation letter and DNA rates from two general practices., Results: TEC of using POCT to deliver a routine NHSHC is lower than the laboratory-led pathway with savings of £29 per 100 invited patients up the point of cardiovascular disease risk score presentation. Use of POCT can deliver NHSHC in one sitting, whereas the laboratory pathway offers patients several opportunities to DNA appointment., Conclusions: TEC of using POCT to deliver an NHSHC in the primary care setting is lower than the laboratory-led pathway. Using POCT minimises DNA rates associated with laboratory testing and enables completion of NHSHC in one sitting., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Cardiovascular disease (CVD) is the leading cause of premature mortality and a major contributor of health inequalities in England. Compared to more affluent and white counterparts, deprived people and ethnic minorities tend to die younger due to preventable CVD associated with lifestyle. In addition, deprived, ethnic minorities and younger people are less likely to be served by CVD prevention services. This study assessed the effectiveness of community-based outreach providers in delivering England's National Health Services (NHS) Health Check programme, a CVD preventive programme to under-served groups., Methods: Between January 2008 and October 2013, community outreach providers delivered a preventive CVD programme to 50,573 individuals, in their local communities, in a single consultation without prescheduled appointments. Community outreach providers operated on evenings and weekends as well as during regular business hours in venues accessible to the general public. After exclusion criteria, we analysed and compared socio-demographic data of 43,177 Health Check attendees with the general population across 38 local authorities (LAs). We assessed variation between local authorities in terms of age, sex, deprivation and ethnicity structures using two sample t-tests and within local authority variation in terms of ethnicity and deprivation using Chi squared tests and two sample t-tests respectively., Results: Using Index of Multiple Deprivation, the mean deprivation score of the population reached by community outreach providers was 6.01 higher (p < 0.05) than the general population. Screened populations in 29 of 38 LAs were significantly more deprived (p < 0.05). No statistically significant difference among ethnic minority groups was observed between LAs. Nonetheless some LAs - namely Leicester, Thurrock, Sutton, South Tyneside, Portsmouth and Gateshead were very successful in recruiting ethnic minority groups. The mean proportion of men screened was 11.39% lower (p < 0.001) and mean proportion of 40-49 and 50-59 year olds was 9.98% and 3.58% higher (p < 0.0001 and p < 0.01 respectively) than the general population across 38 LAs., Conclusions: Community-based outreach providers effectively reach under-served groups by delivering preventive CVD services to younger, more deprived populations, and a representative proportion of ethnic minority groups. If the programme is successful in motivating the under-served groups to improve lifestyle, it may reduce health inequalities therein.

Three-dimensional fluorescence microscopy based on Nyquist sampling of focal planes faces harsh trade-offs between acquisition time, light exposure, and signal-to-noise. We propose a 3D compressed sensing approach that uses temporal modulation of the excitation intensity during axial stage sweeping and can be adapted to fluorescence microscopes without hardware modification. We describe implementations on a lattice light sheet microscope and an epifluorescence microscope, and show that images of beads and biological samples can be reconstructed with a 5-10 fold reduction of light exposure and acquisition time. Our scheme opens a new door towards faster and less damaging 3D fluorescence microscopy.

Objective: To determine coverage of NHS Health Check, a national cardiovascular risk assessment programme in England, in the first four years after implementation, and to examine prevalence of high cardiovascular disease (CVD) risk and uptake of statins in high risk patients., Method: Study sample was 95,571 patients in England aged 40-74years continuously registered with 509 practices in the Clinical Practice Research Datalink between April 2009 and March 2013. Multilevel logistic regression models were used to assess predictors of Health Check attendance; elevated CVD risk factors and statin prescribing among attendees., Results: Programme coverage was 21.4% over four years, with large variations between practices (0%-72.7%) and regions (9.4%-30.7%). Coverage was higher in older patients (adjusted odds ratio 2.88, 95% confidence interval 2.49-3.31 for patients 70-74years) and in patients with a family history of premature coronary heart disease (2.37, 2.22-2.53), but lower in Black Africans (0.75, 0.61-0.92) and Chinese (0.68, 0.47-0.96) compared with White British. Coverage was similar in patients living in deprived and affluent areas. Prevalence of high CVD risk (QRISK2≥20%) among attendees was 4.6%. One third (33.6%) of attendees at high risk were prescribed a statin after Health Checks., Conclusions: Coverage of the programme and statin prescribing in high risk individuals was low. Coverage was similar in deprived and affluent groups but lower in some ethnic minority groups, possibly widening inequalities. These findings raise a question about whether recommendations by WHO to develop CVD risk assessment programmes internationally will deliver anticipated health benefits., (Copyright © 2015. Published by Elsevier Inc.)

Gene expression control results from the combined interactions of the nearly hundred proteins forming the pre-initiation complex, thousands of transcription regulators, and genomic DNA. In the recent years, new technologies have revealed several key aspects of nuclear spatial organization that showed a fine interplay between the function of nuclear proteins, their 3D organization, and their dynamics. Here we review several concepts that link biochemical reactivity in the nucleus to its 3D spatial organization. We present the analogies between the emerging understanding of nuclear organization in the field of cell biology, and the more established disciplines of heterogeneous catalysis and the physics of random walks. We provide several recent examples showing how nuclear geometry affects protein reactivity in the nucleus., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)