Financial incentives for vaccination do not have negative unintended consequences.

Financial incentives to encourage healthy and prosocial behaviours often trigger initial behavioural change1-11, but a large academic literature warns against using them12-16. Critics warn that financial incentives can crowd out prosocial motivations and reduce perceived safety and trust, thereby reducing healthy behaviours when no payments are offered and eroding morals more generally17-24. Here we report findings from a large-scale, pre-registered study in Sweden that causally measures the unintended consequences of offering financial incentives for taking the first dose of a COVID-19 vaccine. We use a unique combination of random exposure to financial incentives, population-wide administrative vaccination records and rich survey data. We find no negative consequences of financial incentives; we can reject even small negative impacts of offering financial incentives on future vaccination uptake, morals, trust and perceived safety. In a complementary study, we find that informing US residents about the existence of state incentive programmes also has no negative consequences. Our findings inform not only the academic debate on financial incentives for behaviour change but also policy-makers who consider using financial incentives to change behaviour.

Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib.

We explored the impact of early molecular response (EMR; BCR-ABL ≤10% on the international scale [BCR-ABL(IS)] at 3 or 6 months) on outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with nilotinib or imatinib based on 4 years of follow up in Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients. Patients (n = 846) received nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, or imatinib 400 mg once daily. At 3 months, more patients had EMR failure (ie, BCR-ABL(IS) >10%) on imatinib (33%) than on nilotinib (9%-11%); similarly at 6 months, 16% of patients in the imatinib arm vs 3% and 7% in the nilotinib arms had EMR failure. In all arms, EMR failure was associated with lower rates of molecular response, an increased risk of progression, and lower overall survival compared with EMR achievement. We also analyzed patient and treatment characteristics associated with EMR and found distinct patterns in the nilotinib arms vs the imatinib arm. High Sokal risk score was associated with a high rate of EMR failure on imatinib, but not on nilotinib. In contrast, reduced dose intensity and dose interruptions were strongly associated with EMR failure in nilotinib-treated, but not imatinib-treated, patients. This study is registered at www.clinicaltrials.gov as #NCT00471497.

Poverty and Economic Decision-Making: Evidence from Changes in Financial Resources at Payday.

We study the effect of financial resources on decision-making. Low-income U.S. households are randomly assigned to receive an online survey before or after payday. The survey collects measures of cognitive function and administers risk and intertemporal choice tasks. The study design generates variation in cash, checking and savings balances, and expenditures. Before-payday participants behave as if they are more present-biased when making intertemporal choices about monetary rewards but not when making intertemporal choices about non-monetary real-effort tasks. Nor do we find before-after differences in risk-taking, the quality of decision-making, the performance in cognitive function tasks, or in heuristic judgments.

Numerical ability predicts mortgage default.

Unprecedented levels of US subprime mortgage defaults precipitated a severe global financial crisis in late 2008, plunging much of the industrialized world into a deep recession. However, the fundamental reasons for why US mortgages defaulted at such spectacular rates remain largely unknown. This paper presents empirical evidence showing that the ability to perform basic mathematical calculations is negatively associated with the propensity to default on one's mortgage. We measure several aspects of financial literacy and cognitive ability in a survey of subprime mortgage borrowers who took out loans in 2006 and 2007, and match them to objective, detailed administrative data on mortgage characteristics and payment histories. The relationship between numerical ability and mortgage default is robust to controlling for a broad set of sociodemographic variables, and is not driven by other aspects of cognitive ability. We find no support for the hypothesis that numerical ability impacts mortgage outcomes through the choice of the mortgage contract. Rather, our results suggest that individuals with limited numerical ability default on their mortgage due to behavior unrelated to the initial choice of their mortgage.

The rubella virus capsid protein inhibits mitochondrial import.

The rubella virus (RV) capsid is an RNA-binding protein that functions in nucleocapsid assembly at the Golgi complex, the site of virus budding. In addition to its role in virus assembly, pools of capsid associate with mitochondria, a localization that is not consistent with virus assembly. Here we examined the interaction of capsid with mitochondria and showed that this viral protein inhibits the import and processing of mitochondrial precursor proteins in vitro. Moreover, RV-infected cells were found to contain lower intramitochondrial levels of matrix protein p32. In addition to inhibiting the translocation of substrates into mammalian mitochondria, capsid efficiently blocked import into yeast mitochondria, thereby suggesting that it acts by targeting a highly conserved component of the translocation apparatus. Finally, mutation of a cluster of five arginine residues in the amino terminus of capsid, though not interfering with its binding to mitochondria, abrogated its ability to block protein import into mitochondria. This is the first report of a viral protein that affects the import of proteins into mitochondria.

Monetary incentives increase COVID-19 vaccinations.

The stalling of COVID-19 vaccination rates threatens public health. To increase vaccination rates, governments across the world are considering the use of monetary incentives. Here we present evidence about the effect of guaranteed payments on COVID-19 vaccination uptake. We ran a large preregistered randomized controlled trial (with 8286 participants) in Sweden and linked the data to population-wide administrative vaccination records. We found that modest monetary payments of 24 US dollars (200 Swedish kronor) increased vaccination rates by 4.2 percentage points (P = 0.005), from a baseline rate of 71.6%. By contrast, behavioral nudges increased stated intentions to become vaccinated but had only small and not statistically significant impacts on vaccination rates. The results highlight the potential of modest monetary incentives to raise vaccination rates.

School and kindergarten attendance and home schooling of pediatric cancer patients before and during the SARS-CoV-2 pandemic: results of a survey of the German Society for Pediatric Oncology and Hematology.

In this multicenter survey (July 07 to August 08, 2020) in pediatric oncology centers (POCs) belonging to the German Society for Pediatric Oncology and Hematology (GPOH), 36 POCs participated (response rate 70.6%). Home schooling practice was judged as satisfying by 79% prior to and by 38% during the pandemic (P=0.0007). The individual risk of a SARS-CoV-2 infection and the risk of transmission to other patients/caregivers were arguments against attendance. Most POCs recommended regular social participation/school attendance after the end of intensive therapy. 81% stated that persisting restrictions result in serious negative psychosocial consequences for the patients and their families. In-hospital school education, home schooling and re-attendance of school and kindergarten among pediatric cancer patients have suffered a severe setback during the SARS-CoV-2 pandemic. Continuous communication and education concerning protective measures as well as an individual risk assessment are required to avoid the detrimental exclusion of pediatric oncology patients from kindergarten and school.

Proline residues of transmembrane domains determine the sorting of inner membrane proteins in mitochondria.

Most inner membrane proteins of mitochondria are synthesized in the cytosol and reach the inner membrane using one of two alternative sorting pathways. On the stop transfer route, proteins are arrested during import at the level of the inner membrane. The conservative sorting pathway involves translocation through the inner membrane and insertion from the matrix. It is unclear how the translocase of the inner membrane 23 protein translocation machinery differentiates between the two classes of proteins. Here we show that proline residues in hydrophobic stretches strongly disfavor the translocation arrest of transmembrane domains (TMDs) and favor the transfer of preproteins to the matrix. We propose that proline residues, together with the hydrophobicity of the TMD and the presence of charged residues COOH-terminally flanking the TMD, are determinants of the intramitochondrial sorting of inner membrane proteins.

Commercial applicability of cell microancapsulation: a review of intellectual property rights.

Maturity and applicability of a distinct field of science can be estimated, using a review of current filing statistics of patent applications. Therefore, hereby a search based on international classifications has been directed to the world intellectual property organization (WIPO) to determine the amount and content of patent applications related to the field of cell microencapsulation. The search was evaluated with regard to the distinct indications envisaged and an evaluation of possible technology gaps for fostering further progress was conducted.

Intravenous tezosentan improves gas exchange and hemodynamics in acute lung injury secondary to meconium aspiration.

OBJECTIVE: Meconium aspiration induces acute lung injury (ALI) and subsequent pulmonary arterial hypertension (PAH) which may lead to right ventricular failure. Increase of endothelin-1, thromboxane-A, and phosphodiesterases are discussed molecular mechanisms. We investigated the intrapulmonary and hemodynamic effects of the intravenous dual endothelin A and B receptor blocker tezosentan and inhalational iloprost in a model of ALI due to meconium aspiration. DESIGN: Animal study. SETTING: University-affiliated research laboratory. SUBJECTS: White farm pigs. INTERVENTIONS: Acute lung injury was induced in 24 pigs by instillation of meconium. Animals were randomly assigned to four groups to receive either intravenous tezosentan, inhalational iloprost, or combined tezosentan and iloprost, or to serve as controls. MEASUREMENTS AND RESULTS: After meconium aspiration-induced lung injury each treatment increased oxyhemoglobin saturations (TEZO: 88 +/- 6% (p = 0.02), ILO: 85 +/- 13% (p = 0.05), TEZO-ILO: 89 +/- 6% (p = 0.02), control: 70 +/- 18%). TEZO but not ILO significantly decreased pulmonary arterial pressure and pulmonary vascular resistance (both p < 0.01). ILO alone decreased intrapulmonary shunt blood flow (p < 0.01). Compared with control, TEZO-ILO yielded the highest arterial partial pressure of oxygen (70 +/- 6 torr vs.49 +/- 9 torr, p = 0.04), although it decreased arterial blood pressure (change from 71 +/- 13 mmHg to 62 +/- 12 mmHg vs.85 +/- 14 mmHg to 80 +/- 11 mmHg (p = 0.01). CONCLUSIONS: Intravenous TEZO improves pulmonary gas exchange and hemodynamics in experimental acute lung injury secondary to meconium aspiration. Inhaled ILO improves gas exchange only, thereby reducing intrapulmonary shunt blood flow. Combination of TEZO and ILO marginally improves pulmonary gas exchange at the disadvantage of pulmonary selectivity.

Ion beam degradation analysis of poly(3-hexylthiophene) (P3HT): can cryo-FIB minimize irradiation damage?

In this study, to assess the influence of the temperature on the ion beam degradation, irradiation experiments on organic semiconductor materials were performed for both cryogenic and room temperature conditions. Thin P3HT films on silicon substrates were exposed to increasing ion doses in dual beam FIB. The degradation behaviour by means of a decrease in the C[double bond, length as m-dash]C band which corresponds to a loss of conjugation was investigated by means of Raman spectroscopy. In addition, atomic force microscopy (AFM) and Kelvin probe force microscopy (KPFM) were used for a characterization of morphology and surface potential which provide information on temperature and ion dose dependent degradation behaviour.

Single-cell-bioreactors as end of miniaturization approaches in biotechnology: progresses with characterised bioreactors and a glance into the future.

Incidents with single cells and their genesis have not been the major focus of science up to now. This fact is supported by the difficulties one faces when wanting to monitor and cultivate small populations of cells in a defined compartment under controlled conditions, in vitro. Several approaches of up- and down-scaling have often led to poorly understood results which might be better elucidated by understanding the cellular genesis as a function of its microenvironment. This review of the approaches of scale-up and scale-down processes illustrates technical possibilities and shows up their limitations with regard to obtainable data for the characterisation of cellular genesis and impact of the cellular microenvironment. For example, stem cell research advances underline the lack of information about the impact of the microenvironment on cellular development. Finally, a proposal of future research efforts is given on how to overcome this lack of data via a novel bioreactor setup.

Conserved N-terminal negative charges in the Tim17 subunit of the TIM23 translocase play a critical role in the import of preproteins into mitochondria.

The TIM23 complex of the mitochondrial inner membrane mediates the import of preproteins that contain positively charged targeting signals. This translocase consists of the two phylogenetically related membrane-embedded subunits Tim17 and Tim23 to which four largely hydrophilic subunits, Tim50, Tim44, Tim16, and Tim14, are attached. Whereas in vitro reconstitution experiments have suggested a pore-forming capacity of recombinant Tim23, virtually nothing is known about the properties and function of Tim17. We employed a combined genetic and biochemical approach to address the function of Tim17 in preprotein translocation. Tim17 exposes an N-terminal hydrophilic stretch into the intermembrane space. Truncation of the first 11 amino acid residues of this stretch did not affect the stability or integrity of TIM23 subunits but strongly impaired the import of preproteins. Moreover, expression of the truncated Tim17 variant led to a dominant negative effect on the mitochondrial membrane potential. By an alanine-scanning approach we identified two conserved negative charges in the N terminus of Tim17 as critical for Tim17 function. The replacement of these positions by positively charged residues results in a strong growth defect, which can be cured by reverting two conserved positive charges into aspartate residues between transmembrane domains two and three of Tim17. On the basis of these observations we propose that charged residues in Tim17 are critical for the preprotein-induced gating of the TIM23 translocase.

Mitochondrial targeting signals and mature peptides of 3-methylcrotonyl-CoA carboxylase.

Inherited deficiency of 3-methylcrotonyl-CoA carboxylase (MCC), an enzyme of leucine degradation, is an organic acidemia detectable by expanded newborn screening with a variable phenotype that ranges from asymptomatic to death in infancy. Here, we show that the two subunits of the enzyme (MCCalpha; MCCbeta) are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences. We identified the cleavage sites (Tyr41/Thr42 and Ala22/Tyr23 for MCCalpha and MCCbeta, respectively) of the targeting signals and the amino-termini of the mature polypeptides of MCC and propionyl-CoA carboxylase, a mitochondrial paralog. The amino-termini containing 39 (MCCalpha) or 20 amino acids (MCCbeta) were both necessary and sufficient for targeting. Structural requirements for mitochondrial import were defined by site-directed mutagenesis. Our studies provide the prerequisite to understand the impact of specific mutations on the clinical phenotype of MCC deficiency.