Long-term effects of the interruption of the Dutch breast cancer screening program due to COVID-19:A modelling study

Due to COVID-19, the Dutch breast cancer screening program was interrupted for three months with uncertain long-term effects. The aim of this study was to estimate the long-term impact of this interruption on delay in detection, tumour size of screen-detected breast cancers, and interval cancer rate. After validation, the micro-simulation model SiMRiSc was used to calculate the effects of interruption of the breast cancer screening program for three months and for hypothetical interruptions of six and twelve months. A scenario without interruption was used as reference. Outcomes considered were tumour size of screen-detected breast cancers and interval cancer rate. Women of 55–59 and 60–64 years old at time of interruption were considered. Uncertainties were estimated using a sensitivity analysis. The three-month interruption had no clinically relevant long-term effect on the tumour size of screen-detected breast cancers. A 19% increase in interval cancer rate was found between last screening before and first screening after interruption compared to no interruption. Hypothetical interruptions of six and twelve months resulted in larger increases in interval cancer rate of 38% and 78% between last screening before and first screening after interruption, respectively, and an increase in middle-sized tumours in first screening after interruption of 26% and 47%, respectively. In conclusion, the interruption of the Dutch screening program is not expected to result in a long-term delay in detection or clinically relevant change in tumour size of screen-detected cancers, but only affects the interval cancer rate between last screening before and first screening after interruption

A Socio-Spatial Survey of Water Issues in Makondo Parish, Uganda

This report details some of the key findings of a sociological survey that was undertaken in rural Makondo Parish, Lwengo District in Uganda. The cross-sectional survey was carried out between September and November 2011 and covered all the 15 villages in the Parish. The broad aim of the survey was to assess the livelihoods, health, gender and water governance issues in Makondo Parish. Prior to the survey, several preliminary visits were made to the study area, which were then followed by a rigorous literature review on rural water governance, health and livelihoods in Uganda and globally so as to identify the major themes and variables. These themes were then used to develop a quantitative or structured questionnaire. The questionnaire was structured under the following headings: household and interviewer identification; respondents’ characteristics; household livelihoods and well-being, particularly poverty indicators like main source of income, money earned, dwelling type, and number of meals eaten; knowledge of the importance of safe water; access to safe water, such as type of water sources used, access to improved water sources, transportation of water; health issues like water-related diseases suffered, cost to the household of these diseases, steps taken to mitigate against the diseases; knowledge of hand-pump functionality; household water use and management, such as satisfaction with use, conflicts if any and decision-making on use; perceptions of safe water services and systems such as rating of safe water service delivery and why; knowledge of community-based water management systems and capacity building for sustainable utilisation of safe water. The final version was translated into Luganda, the local vernacular so as not to distort the meaning of the questions. This exercise was carried out by the Makerere University Institute of Languages, and the Luganda version was then used to train the Community Health Workers on how to administer and record standardised interviews, such as mastering the intended meaning of each and every question in the questionnaire, the expected data, recording and editing among others. The CHWs were also trained on how to use a GPS (Global Positioning System) unit so as to capture the necessary data for mapping the household locations. After training the CHWs, the questionnaire was piloted in one of the villages in a neighbouring Parish (called Nanywa) and again revised. The actual field work or data collection started with Misaana village in the North-Eastern part of Makondo Parish, then moved on to Luyiiyi-Kate, Luyiiyi-Protazio and ended with Kiguluka, the last village in the Parish on 14th November 2011. It took between three to four days on average to complete the survey in each village, and the first day of work in each village involved meeting the Village Chairpersons, explaining to then about the WIL Project, objectives of the survey and seeking their support in locating selected households for interviews. After every two-three days of data collection, meetings were held with the interviewers/CHWs to share fieldwork experiences as well as edit field questionnaires. A total of six hundred and six (606) households selected proportionately across the 15 villages in Makondo Parish were covered in the survey. Despite several challenges that were met during the survey, such as failure by interviewers/CHWs to complete their assigned households in time; heavy rains that made driving on the village roads quite difficult especially in Kiteredde, Kiyumbakimu and Kiguluka villages, the survey was a success and data collection ended quite successfully, as the originally targeted sample was attained

Spherical harmonic decomposition applied to spatial-temporal analysis of human high-density EEG

We demonstrate an application of spherical harmonic decomposition to analysis of the human electroencephalogram (EEG). We implement two methods and discuss issues specific to analysis of hemispherical, irregularly sampled data. Performance of the methods and spatial sampling requirements are quantified using simulated data. The analysis is applied to experimental EEG data, confirming earlier reports of an approximate frequency-wavenumber relationship in some bands.Comment: 12 pages, 8 figures, submitted to Phys. Rev. E, uses APS RevTeX style

Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-beta plaques

BACKGROUND: Increasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer’s disease comes from molecular and functional studies in rodent models. However, these models may not fully recapitulate human disease as human and rodent astrocytes differ considerably in morphology, functionality, and gene expression. RESULTS: To address these challenges, we established an approach to study human astrocytes within the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived astrocyte progenitors into neonatal brains. Xenografted hiPSC-derived astrocyte progenitors differentiated into astrocytes that integrated functionally within the mouse host brain and matured in a cell-autonomous way retaining human-specific morphologies, unique features, and physiological properties. In Alzheimer´s chimeric brains, transplanted hiPSC-derived astrocytes responded to the presence of amyloid plaques undergoing morphological changes that seemed independent of the APOE allelic background. CONCLUSIONS: In sum, we describe here a promising approach that consist of transplanting patient-derived and genetically modified astrocytes into the mouse brain to study human astrocyte pathophysiology in the context of Alzheimer´s disease

Topographical Organization of Mu and Beta Band Activity Associated with Hand and Foot Movements in Patients with Perirolandic Lesions

To study the topographical organization of mu and beta band event-related desynchronization (ERD) associated with voluntary hand and foot movements, we used magnetoencephalographic (MEG) recordings from 19 patients with perirolandic lesions. Synthetic aperture magnetometry (SAM) was used to detect and localize changes in the mu (7 - 11 Hz) and beta (13 - 30 Hz) frequency bands associated with repetitive movements of the hand and foot and overlaid on individual coregistered magnetic resonance (MR) images. Hand movements showed homotopic and contralateral ERD at the sensorimotor (S/M) cortex in the majority of cases for mu and to a lesser extent for beta rhythms. Foot movements showed an increased heterotopic distribution with bilateral and ipsilateral ERD compared to hand movements. No systematic topographical segregation between mu and beta ERD could be observed. In patients with perirolandic lesions, the mu and beta band spatial characteristics associated with hand movements retain the expected functional-anatomical boundaries to a large extent. Foot movements have altered patterns of mu and beta band ERD, which may give more insight into the differential functional role of oscillatory activity in different voluntary movements

Diagnosis of Cystic Fibrosis in Screened Populations

Objective Cystic fibrosis (CF) can be difficult to diagnose, even when newborn screening (NBS) tests yield positive results. This challenge is exacerbated by the multitude of NBS protocols, misunderstandings about screening vs diagnostic tests, and the lack of guidelines for presumptive diagnoses. There is also confusion regarding the designation of age at diagnosis. Study design To improve diagnosis and achieve standardization in definitions worldwide, the CF Foundation convened a committee of 32 experts with a mission to develop clear and actionable consensus guidelines on diagnosis of CF with an emphasis on screened populations, especially the newborn population. A comprehensive literature review was performed with emphasis on relevant articles published during the past decade. Results After reviewing the common screening protocols and outcome scenarios, 14 of 27 consensus statements were drafted that apply to screened populations. These were approved by 80% or more of the participants. Conclusions It is recommended that all diagnoses be established by demonstrating dysfunction of the CF transmembrane conductance regulator (CFTR) channel, initially with a sweat chloride test and, when needed, potentially with newer methods assessing membrane transport directly, such as intestinal current measurements. Even in babies with 2 CF-causing mutations detected via NBS, diagnosis must be confirmed by demonstrating CFTR dysfunction. The committee also recommends that the latest classifications identified in the Clinical and Functional Translation of CFTR project [http://www.cftr2.org/index.php] should be used to aid with CF diagnosis. Finally, to avoid delays in treatment, we provide guidelines for presumptive diagnoses and recommend how to determine the age of diagnosis