Assessing the effectiveness of non-pharmaceutical interventions (NPIs) to mitigate the spread of SARS-CoV-2 is critical to inform future preparedness response plans. Here we quantify the impact of ...6,068 hierarchically coded NPIs implemented in 79 territories on the effective reproduction number, R
, of COVID-19. We propose a modelling approach that combines four computational techniques merging statistical, inference and artificial intelligence tools. We validate our findings with two external datasets recording 42,151 additional NPIs from 226 countries. Our results indicate that a suitable combination of NPIs is necessary to curb the spread of the virus. Less disruptive and costly NPIs can be as effective as more intrusive, drastic, ones (for example, a national lockdown). Using country-specific 'what-if' scenarios, we assess how the effectiveness of NPIs depends on the local context such as timing of their adoption, opening the way for forecasting the effectiveness of future interventions.
Active mobility is considered a key aspect of the mobility revolution and is therefore elementary in combating the climate crisis. However, a lot of research is needed to improve the situation of ...active mobility, especially concerning inhibiting factors in the choice of active means of transport. For reasons such as the high volume and speed of motorised traffic, heavy noise, and pollution levels, urban space is often associated with increased stress. The generation and provision of stress data are therefore of particularly high importance for urban planning. The citizen-science approach of the BMDV1- project ESSEM implements a triangulating approach that uses biological markers and standardized questionnaires to make statements about individual ‘stress’. In the future, this should help identify vulnerable groups and better address them in project development and planning. The presented study describes the use of participatory methods based on three ‘stress hotspots’ in Osnabrück, taking into account different forms of cycling infrastructure.
Multimorbidity, the co-occurrence of two or more diseases in one patient, is a frequent phenomenon. Understanding how different diseases condition each other over the lifetime of a patient could ...significantly contribute to personalised prevention efforts. However, most of our current knowledge on the long-term development of the health of patients (their disease trajectories) is either confined to narrow time spans or specific (sets of) diseases. Here, we aim to identify decisive events that potentially determine the future disease progression of patients.
Health states of patients are described by algorithmically identified multimorbidity patterns (groups of included or excluded diseases) in a population-wide analysis of 9,000,000 patient histories of hospital diagnoses observed over 17 years. Over time, patients might acquire new diagnoses that change their health state; they describe a disease trajectory. We measure the age- and sex-specific risks for patients that they will acquire certain sets of diseases in the future depending on their current health state.
In the present analysis, the population is described by a set of 132 different multimorbidity patterns. For elderly patients, we find 3 groups of multimorbidity patterns associated with low (yearly in-hospital mortality of 0.2-0.3%), medium (0.3-1%) and high in-hospital mortality (2-11%). We identify combinations of diseases that significantly increase the risk to reach the high-mortality health states in later life. For instance, in men (women) aged 50-59 diagnosed with diabetes and hypertension, the risk for moving into the high-mortality region within 1 year is increased by the factor of 1.96 ± 0.11 (2.60 ± 0.18) compared with all patients of the same age and sex, respectively, and by the factor of 2.09 ± 0.12 (3.04 ± 0.18) if additionally diagnosed with metabolic disorders.
Our approach can be used both to forecast future disease burdens, as well as to identify the critical events in the careers of patients which strongly determine their disease progression, therefore constituting targets for efficient prevention measures. We show that the risk for cardiovascular diseases increases significantly more in females than in males when diagnosed with diabetes, hypertension and metabolic disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Many studies on cancer patients investigate the impact of treatment on health-related quality of life (QoL). Typically, QoL is measured longitudinally, at baseline and at predefined ...timepoints thereafter. The question is whether, at a given timepoint, patients who return their questionnaire (available cases, AC) have a different QoL than those who do not return their questionnaire (non-AC).
Methods
We employed augmented inverse probability weighting (AIPW) to estimate the average QoL of non-AC in two studies on advanced-stage cancer patients. The AIPW estimator assumed data to be missing at random (MAR) and used machine learning (ML)-based methods to estimate answering probabilities of individuals at given timepoints as well as their reported QoL, as a function of auxiliary variables. These auxiliary variables were selected by medical oncologists based on domain expertise. We aggregated results both by timepoint and by time until death and compared AIPW estimates to the AC averages. Additionally, we used a pattern mixture model (PMM) to check sensitivity of our AIPW estimates against violation of the MAR assumption.
Results
Our study included 1927 patients with advanced pancreatic and 797 patients with advanced breast cancer. The AIPW estimate for average QoL of non-AC was below the average QoL of AC when aggregated by timepoint. The difference vanished when aggregated by time until death. PMM estimates were below AIPW estimates.
Conclusions
Our results indicate that non-AC have a lower average QoL than AC. However, estimates for QoL of non-AC are subject to unverifiable assumptions about the missingness mechanism.
Abstract There are no clear guidelines regarding the optimal treatment sequence for advanced pancreatic cancer, as head‐to‐head phase III randomised trials are missing. We assess real‐world ...effectiveness of three common sequential treatment strategies by emulating a hypothetical randomised trial. This analysis included 1551 patients with advanced pancreatic cancer from the prospective, clinical cohort study Tumour Registry Pancreatic Cancer receiving FOLFIRINOX ( n = 613) or gemcitabine/nab‐paclitaxel (GEMNAB; n = 938) as palliative first‐line treatment. We used marginal structural modelling to compare overall survival (OS) and time to deterioration (TTD) of health‐related quality of life (HRQoL) between three common first‐ to second‐line treatment sequences, adjusting for time‐varying potential confounding. The sequences were: FOLFIRINOX→GEMNAB, GEMNAB→FOLFOX/OFF and GEMNAB→nanoliposomal irinotecan (NALIRI) + 5‐fluorouracil. Outcome was also calculated stratified by patients' prognostic risk according to the Pancreatic Cancer Score. Median OS and TTD of HRQoL independent of risk were 10.7 8.9, 11.9 and 6.4 4.8, 7.7 months for FOLFIRINOX→GEMNAB, 8.4 7.4, 9.7 and 5.8 4.6, 7.1 months for GEMNAB→FOLFOX/OFF and 8.9 7.8, 10.4 and 4.6 4.1, 6.1 months for GEMNAB→NALIRI+5‐fluorouracil. Compared to FOLFIRINOX→GEMNAB, OS and TTD were worse for poor‐risk patients with GEMNAB→FOLFOX/OFF (OS: HR 2.09 1.47, 2.98; TTD: HR 1.97 1.19, 3.27) and those with GEMNAB→NALIRI+5‐fluorouracil (OS: HR 1.35, 0.76, 2.39; TTD: HR 2.62 1.56, 4.42). Brackets denote 95%‐confidence intervals. The estimated real‐world effectiveness of the three treatment sequences evaluated were largely comparable. Poor‐risk patients might benefit from intensified treatment with FOLFIRINOX→GEMNAB in terms of clinical and patient‐reported outcomes. Future randomised trials on sequential treatments in advanced pancreatic cancer are warranted.
We introduce a deformed version of Dyck paths (DDP), where additional to the steps allowed for Dyck paths, ‘jumps’ orthogonal to the preferred direction of the path are permitted. We consider the ...generating function of DDP, weighted with respect to their half-length, area and number of jumps. This represents the first example of an exactly solvable two-dimensional lattice vesicle model showing a higher-order multicritical point. Applying the generalized method of steepest descents, we see that the associated two-variable scaling function is given by the logarithmic derivative of a generalized (higher-order) Airy integral.
Denne masteroppgaven handler om hvordan pedagogiske ledere i barnehagen stimulerer til barns læring. Oppgavens utgangspunkt har vært Rammeplan for barnehagens innhold og oppgaver (2006), og dens vekt ...på barns læring. Det presenteres også relevante politiske dokumenter som har betydning for barnehagens virksomhet.
Studien er basert på empirisk materiale, der datainnsamlingen har foregått ved kvalitative forskningsintervju av tre pedagogiske ledere i ulike barnehager. Ut fra de tre intervjuene så jeg tre felles kategorier som kjennetegner det pedagogiske arbeidet i barnehagen. Disse tre kategoriene er: observasjon, barns medvirkning og mestring . Den første kategorien i undersøkelsen viser at de pedagogiske lederne gjennomfører en omfattende observasjon av barnet, dette for å kunne vite hva og hvordan stimulere til læring. Den andre viser at det enkelte barns meninger og interesser blir tatt hensyn til slik at barnet får utvikle seg på de områder det er opptatt av. Den tredje kategorien viser at de pedagogiske lederne sørger i størst mulig grad for at miljøet blir utformet slik at alle barn får muligheten til å få en opplevelse av mestring. Konklusjonen av denne studien er at pedagogiske ledere i barnehagen stimulerer til barns læring ved å tilrettelegge miljøet ut fra det enkelte barnets behov.
Denne masteroppgaven handler om hvordan pedagogiske ledere i barnehagen stimulerer til barns læring. Oppgavens utgangspunkt har vært Rammeplan for barnehagens innhold og oppgaver (2006), og dens vekt på barns læring. Det presenteres også relevante politiske dokumenter som har betydning for barnehagens virksomhet.
Studien er basert på empirisk materiale, der datainnsamlingen har foregått ved kvalitative forskningsintervju av tre pedagogiske ledere i ulike barnehager. Ut fra de tre intervjuene så jeg tre felles kategorier som kjennetegner det pedagogiske arbeidet i barnehagen. Disse tre kategoriene er: observasjon, barns medvirkning og mestring . Den første kategorien i undersøkelsen viser at de pedagogiske lederne gjennomfører en omfattende observasjon av barnet, dette for å kunne vite hva og hvordan stimulere til læring. Den andre viser at det enkelte barns meninger og interesser blir tatt hensyn til slik at barnet får utvikle seg på de områder det er opptatt av. Den tredje kategorien viser at de pedagogiske lederne sørger i størst mulig grad for at miljøet blir utformet slik at alle barn får muligheten til å få en opplevelse av mestring. Konklusjonen av denne studien er at pedagogiske ledere i barnehagen stimulerer til barns læring ved å tilrettelegge miljøet ut fra det enkelte barnets behov.
This master crawl deals with the teaching of a child’s læring. The opposition gangway has vært Rammeplan for barnehagens innhold og oppgaver (2006), og dens vect on children’s læring. It is presented with a good sense of political doctrine that has a meaning for the virginity of childcare.
The studies are based on empirical materials, der dataine collection has foregone wood qualitative research interview of three pedagogical students in ulike barnehager. Out fra the three interviewed so jeg three felles categories as kjennetegner the pedagogical heritage in the kindergarten. Disse three categories you: observasjon, children’s contagion og mestring The første categorien in the miracle viser at de pedagogiske lederne gjennomfører a covered observasjon of the child, dette for å kunne vite hva og hvordan stimulere til læring. The other viser at the single child’s meninger og interesser becomes tatt hensyn til slik at the child gets out of touch on the areas it you opptatt of. The third category sees at de pedagogiske lederne sørger in størst mulig grad for at köøet becomes the design slik at alle children get the muktii til å get an upswing of mestring. The conclus ion of this study you at pedagogical stage in the kindergarten stimuli til barn læring ved å tilrettelegge köøet ut fra the single child’s needs.
Denne masteroppgaven handler om hvordan pedagogiske ledere i barnehagen stimulerer til barns læring. Oppgavens utgangspunkt har vært Rammeplan for barnehagens innhold og oppgaver (2006), og dens vekt ...på barns læring. Det presenteres også relevante politiske dokumenter som har betydning for barnehagens virksomhet. Studien er basert på empirisk materiale, der datainnsamlingen har foregått ved kvalitative forskningsintervju av tre pedagogiske ledere i ulike barnehager. Ut fra de tre intervjuene så jeg tre felles kategorier som kjennetegner det pedagogiske arbeidet i barnehagen. Disse tre kategoriene er: observasjon, barns medvirkning og mestring. Den første kategorien i undersøkelsen viser at de pedagogiske lederne gjennomfører en omfattende observasjon av barnet, dette for å kunne vite hva og hvordan stimulere til læring. Den andre viser at det enkelte barns meninger og interesser blir tatt hensyn til slik at barnet får utvikle seg på de områder det er opptatt av. Den tredje kategorien viser at de pedagogiske lederne sørger i størst mulig grad for at miljøet blir utformet slik at alle barn får muligheten til å få en opplevelse av mestring. Konklusjonen av denne studien er at pedagogiske ledere i barnehagen stimulerer til barns læring ved å tilrettelegge miljøet ut fra det enkelte barnets behov.
Loss of sensory hair cells leads to deafness and balance deficiencies. In contrast to mammalian hair cells, zebrafish ear and lateral line hair cells regenerate from poorly characterized support ...cells. Equally ill-defined is the gene regulatory network underlying the progression of support cells to differentiated hair cells. scRNA-Seq of lateral line organs uncovered five different support cell types, including quiescent and activated stem cells. Ordering of support cells along a developmental trajectory identified self-renewing cells and genes required for hair cell differentiation. scRNA-Seq analyses of
mutants, in which hair cell regeneration is increased, demonstrates that Fgf and Notch signaling inhibit proliferation of support cells in parallel by inhibiting Wnt signaling. Our scRNA-Seq analyses set the foundation for mechanistic studies of sensory organ regeneration and is crucial for identifying factors to trigger hair cell production in mammals. The data is searchable and publicly accessible via a web-based interface.
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