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Philip J Smith

Publications and source records attributed to Philip J Smith.

At least 19 recordsLinked to original sources

An increased specificity score matrix for the prediction of SF2/ASF-specific exonic splicing enhancers.

Numerous disease-associated point mutations exert their effects by disrupting the activity of exonic splicing enhancers (ESEs). We previously derived position weight matrices to predict putative ESEs specific for four human SR proteins. The score matrices are part of ESEfinder, an online resource to identify ESEs in query sequences. We have now carried out a refined functional SELEX screen for motifs that can act as ESEs in response to the human SR protein SF2/ASF. The test BRCA1 exon under selection was internal, rather than the 3'-terminal IGHM exon used in our earlier studies. A naturally occurring heptameric ESE in BRCA1 exon 18 was replaced with two libraries of random sequences, one seven nucleotides in length, the other 14. Following three rounds of selection for in vitro splicing via internal exon inclusion, new consensus motifs and score matrices were derived. Many winner sequences were demonstrated to be functional ESEs in S100-extract-complementation assays with recombinant SF2/ASF. Motif-score threshold values were derived from both experimental and statistical analyses. Motif scores were shown to correlate with levels of exon inclusion, both in vitro and in vivo. Our results confirm and extend our earlier data, as many of the same motifs are recognized as ESEs by both the original and our new score matrix, despite the different context used for selection. Finally, we have derived an increased specificity score matrix that incorporates information from both of our SF2/ASF-specific matrices and that accurately predicts the exon-skipping phenotypes of deleterious point mutations.

Alternative Splicing↗

Measuring immunization coverage among preschool children: past, present, and future opportunities.

Control of vaccine-preventable diseases depends on maintaining high levels of immunization coverage. Immunization coverage among preschool children remains suboptimal in some areas and sociodemographic subgroups, as well as for more recently introduced vaccines, leaving susceptible young children vulnerable to complications from vaccine-preventable diseases. This paper reviews approaches historically used to measure immunization coverage among preschool children in the United States. The strengths and weaknesses of various approaches to measuring immunization coverage among preschool children are explored, with emphasis on the current means to measure national immunization coverage-the National Immunization Survey. Methods for measuring immunization coverage among preschool children at local and state levels are also evaluated. Future opportunities and challenges for measuring immunization coverage at the local, state, and national levels are explored.

Centers for Disease Control and Prevention, U.S.↗

Associations between childhood vaccination coverage, insurance type, and breaks in health insurance coverage.

OBJECTIVES: This study explored how vaccination coverage is associated with not being insured and with insurance type among children who are insured and to show how these associations are modified by race/ethnicity. METHODS: We determined whether 8324 children sampled in the National Immunization Survey in 2001 and 2002 were covered by private insurance only, Medicaid/State Children's Health Insurance Program, or another insurance type or were uninsured at the time of the National Immunization Survey interview or were uninsured at some time before the interview. Children were up to date if, by the date of the interview, their vaccination providers had administered > or =4 doses of diphtheria-tetanus toxoids-acellular pertussis vaccine, > or =3 doses of polio vaccine, > or =1 dose of measles-mumps-rubella vaccine, > or =3 doses of Haemophilus influenzae type b vaccine, and > or =3 doses of hepatitis B vaccine. To evaluate the association between insurance type and breaks in insurance with timely completion of the recommended vaccination schedule soon after 19 months of age, we restricted our analyses to children 19 to 24 months of age. RESULTS: Nationally, 12.6 +/- 1.6% of all children 19 to 24 months of age were uninsured at some time. Children who were uninsured at the time of the National Immunization Survey interview had significantly lower vaccination coverage than did children with Medicaid/State Children's Health Insurance Program coverage or children with private insurance only (52.6% vs 70.0% and 75.6%). Children who had never been insured and children who were insured but had a break in insurance coverage in the 12 months immediately preceding the National Immunization Survey interview had significantly lower vaccination coverage than did children who had been insured continuously (47.4% and 64.8% vs 73.5%). CONCLUSIONS: Approximately 1 of 8 children were uninsured at some time, and those children were at greater risk of not being vaccinated on time as recommended.

Black or African American↗

Association between health care providers' influence on parents who have concerns about vaccine safety and vaccination coverage.

OBJECTIVES: Parents who have concerns about vaccine safety may be reluctant to have their children vaccinated. The purpose of this study was to explore how vaccination coverage among children 19 to 35 months of age is associated with health care providers' influence on parents' decision to vaccinate their children, and with parents' beliefs about vaccine safety. METHODS: Parents of 7695 children 19 to 35 months of age sampled by the National Immunization Survey were administered the National Immunization Survey Parental Knowledge Module between the third quarter of 2001 and the fourth quarter of 2002. Health care providers were defined as a physician, nurse, or any other type of health care professional. Parents provided responses that summarized the degree to which they believed vaccines were safe, and the influence providers had on their decisions to vaccinate their children. Children were determined to be up-to-date if their vaccination providers reported administering > or = 4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine, > or = 3 doses of polio vaccine, > or = 1 dose of measles-mumps-rubella vaccine, > or = 3 doses of Haemophilus influenzae type b vaccine, and > or = 3 doses of hepatitis B vaccine. RESULTS: Of all of the parents, 5.7% thought that vaccines were not safe, and 21.5% said that their decision to vaccinate their children was not influenced by a health care provider. Compared with parents who responded that providers were not influential in their decision to vaccinate their children, parents who responded that providers were influential were twice as likely to respond that vaccines were safe for children. Among children whose parents believed that vaccines were not safe, those whose parents' decision to vaccinate was influenced by a health care provider had an estimated vaccination coverage rate that was significantly higher than the estimated coverage rate among children whose parents' decision was not influenced by a health care provider (74.4% vs 50.3%; estimated difference: 24.1%). CONCLUSIONS: Health care providers have a positive influence on parents to vaccinate their children, including parents who believe that vaccinations are unsafe. Physicians, nurses, and other health care professionals should increase their efforts to build honest and respectful relationships with parents, especially when parents express concerns about vaccine safety or have misconceptions about the benefits and risks of vaccinations.

Child, Preschool↗

Distribution of SR protein exonic splicing enhancer motifs in human protein-coding genes.

Exonic splicing enhancers (ESEs) are pre-mRNA cis-acting elements required for splice-site recognition. We previously developed a web-based program called ESEfinder that scores any sequence for the presence of ESE motifs recognized by the human SR proteins SF2/ASF, SRp40, SRp55 and SC35 (http://rulai.cshl.edu/tools/ESE/). Using ESEfinder, we have undertaken a large-scale analysis of ESE motif distribution in human protein-coding genes. Significantly higher frequencies of ESE motifs were observed in constitutive internal protein-coding exons, compared with both their flanking intronic regions and with pseudo exons. Statistical analysis of ESE motif frequency distributions revealed a complex relationship between splice-site strength and increased or decreased frequencies of particular SR protein motifs. Comparison of constitutively and alternatively spliced exons demonstrated slightly weaker splice-site scores, as well as significantly fewer ESE motifs, in the alternatively spliced group. Our results underline the importance of ESE-mediated SR protein function in the process of exon definition, in the context of both constitutive splicing and regulated alternative splicing.

Alternative Splicing↗

Methods for capture-recapture analysis when cases lack personal identifiers.

Methods for estimating the size of a closed population from a capture-recapture study require the availability of unique identifiers on each of two lists. These identifiers are used to identify the number of individuals appearing on both lists. When the number of individuals appearing on both lists cannot be determined with certainty from the data, matching between the lists is problematic. In this paper, we develop a weighted estimator to account for all possible matches between two lists. A bootstrap procedure is proposed for estimation. To illustrate the methods, we used two lists that recorded New York State (NYS) hospitalizations due to pertussis in 1996 to estimate the number of persons hospitalized for pertussis in NYS that year.

Algorithms↗

Ranking states' immunization coverage: an example from the National Immunization Survey.

The National Immunization Survey (NIS) provides state-level estimates of preschool immunization coverage. These coverages are frequently presented in ranked lists, and ranks are frequently over-interpreted. In this paper, we highlight the difficulty in interpreting ranked point estimates. To demonstrate the uncertainty of ranks, parametric bootstrap methods were used to derive 90 per cent confidence intervals for ranks of state vaccination coverage levels among preschool children. We graphically compared states to a reference state. If NIS data are used to rank states, one should consider presenting confidence intervals for rank and the results of comparisons of one state with another graphically.

Child, Preschool↗

Parent attitudes toward immunizations and healthcare providers the role of information.

BACKGROUND: Lack of information has been associated with patient anxiety or concern in a number of healthcare areas. OBJECTIVES: (1) Identify the proportion of parents who agreed, were neutral, and disagreed that they had access to enough information to make a decision about immunizing their child; (2) examine how parents who agreed and disagreed differed with respect to sociodemographic characteristics, and their attitudes about immunizations, their child's healthcare provider, immunization requirements/exemptions, and immunization policymakers; and (3) identify if differences exist in specific immunization concerns. METHODS: A sample of parents with at least one child aged < or =6 years (n=642) was analyzed using data from the HealthStyles survey conducted during July and August 2003. Odds ratios and the Mantel-Haenszel chi-square test were used for analysis. RESULTS: Response rate for HealthStyles was 69% (4035/5845). The largest proportion of parents agreed they had access to enough information (67%) compared to parents who were neutral (20%) or who disagreed (13%). Compared to parents who agreed, parents who disagreed were more likely to be less confident in the safety of childhood vaccines (odds ratio [OR]=5.4, 95% confidence interval [CI]=3.3-8.9), and to disagree that their child's main healthcare provider is easy to talk to (OR=10.3, 95% CI=3.7-28.1). There was a significant linear trend in the percentage of parents expressing immunization concerns among those who agreed, were neutral, and who disagreed they had access to enough information (p<0.05; df=1). CONCLUSIONS: While most parents agreed that they had access to enough immunization information, approximately a third did not. Perceived lack of information was associated with negative attitudes about immunizations and toward healthcare providers. Basic information about the benefits and risks of vaccines presented by a trusted provider could go a long way toward maintaining and/or improving confidence in the immunization process.

Adolescent↗

The association between having a medical home and vaccination coverage among children eligible for the vaccines for children program.

BACKGROUND: The Vaccines for Children (VFC) program is designed to reduce the cost of vaccines for vulnerable children, including Medicaid-eligible children, American Indian/Alaska Native children, uninsured children, and underinsured children whose health insurance does not cover the cost of vaccinations. A desired consequence of the program is to promote comprehensive continuous medical care within a medical home for these children. OBJECTIVES: To explore how having a medical home is associated with vaccination coverage among children eligible for the program. PARTICIPANTS: A total of 24514 children 19 to 35 months of age sampled by the National Immunization Survey. DESIGN: VFC eligibility was evaluated for 24514 children 19 to 35 months of age who were sampled by the National Immunization Survey. Children were considered to have a medical home if they had a doctor, nurse, or physician's assistant who provided them with ongoing routine care, including well-child care, preventive care, and sick care, according to their parents. Sampled children were determined to be 4:3:1:3:3 up-to-date (UTD) if their vaccination providers reported administering >or=4 doses of diphtheria-tetanus toxoids-acellular pertussis vaccine, >or=3 doses of polio vaccine, >or=1 dose of measles-mumps-rubella vaccine, >or=3 doses of Haemophilus influenzae type b vaccine, and >or=3 doses of hepatitis B vaccine. RESULTS: Nationally, 44.9% of all children were VFC eligible and 93.0% of the VFC-eligible children received all vaccine doses at a provider enrolled in the VFC program. Compared with children who were not VFC eligible, VFC-eligible children were less likely to be UTD (70.8% vs 77.7%) and less likely to have a medical home (82.1% vs 95.0%). However, among VFC-eligible children, children who had a medical home were significantly more likely to be UTD, compared with children who did not have a medical home (72.3% vs 63.5%). Also, among VFC-eligible children who had a medical home, children who used their medical home consistently to receive all of their vaccination doses were significantly more likely to be UTD, compared with children who did not receive all of their doses from their medical home (75.3% vs 65.7%). Finally, the 4:3:1:3:3 vaccination coverage rate among VFC-eligible children who received all of their vaccination doses from their medical home was not significantly different from that among non-VFC-eligible children, after controlling for significant differences in sociodemographic factors between these groups (adjusted difference: 2.8%; 95% confidence interval: -0.1% to 5.7%). CONCLUSIONS: Although the vaccination coverage rate among VFC-eligible children who had a medical home and received all vaccine doses from their medical home was essentially equivalent to that of non-VFC-eligible children, substantial percentages of VFC-eligible children either did not have a medical home or did not use their medical home to receive all of their recommended vaccinations. The vaccination coverage rate among these children was significantly lower. This suggests that there may be opportunities to increase vaccination coverage by removing barriers that prevent the adoption and consistent use of a medical home among these children.

Child Health Services↗

Statistical methodology of the National Immunization Survey, 1994-2002.

OBJECTIVES: Since 1994 the National Immunization Survey (NIS) has monitored progress toward the Healthy People 2000 and 2010 vaccination goals. The NIS collects data in two phases: first, a random-digit-dialing (RDD) telephone survey to identify households with children 19-35 months old and, second, a mail survey to vaccination providers to obtain vaccination histories used to estimate vaccination coverage rates. This report reviews the methodologies used in the 1994-2002 NIS to obtain official estimates of vaccination coverage and describes the methodology used for the first three topical modules of the NIS. METHODS: From 1994 to 1997 the NIS used a variation of a two-phase estimator to compensate for missing provider-reported vaccination histories. Between 1998 and 2001 a weighting-class estimator was used. In 2002 and thereafter the weighting-class approach was refined to account for households that do not have telephones and for unvaccinated children. To collect data on immunization-related topics, the NIS sample was randomized among three topical modules: health insurance and ability to pay for vaccinations (HIM); parental knowledge and experiences about vaccinations (PKM); and daycare attendance, breastfeeding practices, and participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (DCM). RESULTS: In 2001 among children with completed RDD interviews, 0.3 percent were entirely unvaccinated. Together, the new nontelephone adjustment and the refinement for unvaccinated children yielded revised estimates that were within 1.5 percentage points of the original estimates obtained using the 1998-2001 methodology. Over the six quarters during which the first three topical modules were fielded (from mid-2001 through 2002), 21,163 children were randomized to the HIM, 3576 to the PKM, and 3511 to the DCM.

Adolescent↗

Evaluation of invalid vaccine doses.

BACKGROUND: The 2002 Recommended Childhood Immunization Schedule clarified the definition of an invalid dose of vaccine as any dose administered >/=5 days before the minimum age or interval had elapsed. Any invalid dose of vaccine should be repeated. OBJECTIVE: Determine the proportion of U.S. children who received an invalid dose of vaccine, evaluate the impact on vaccination coverage levels if invalid doses were not counted, and determine the vaccine purchase cost if at least one invalid dose is repeated. METHODS: Provider-reported vaccination histories of children aged 19 to 35 months sampled by the 2000 National Immunization Survey were evaluated. Analyses were performed in 2002 after the 2002 Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule was released. Any vaccine dose administered >/=5 days before the recommended minimum age or interval was classified as invalid. Change in vaccination coverage was determined by subtracting estimated valid-dose coverage (based on number of valid doses received) from the estimated up-to-date coverage (based on number of doses received regardless of age or spacing). RESULTS: Overall, 10.5% (+/-0.6%) of children had received at least one invalid dose of vaccine. Of the invalid doses, 51% were hepatitis B, 100% of which were the third dose; 19% were diphtheria-tetanus-pertussis (DTP/DTaP), 92% of which were the fourth dose; 12% were measles-containing vaccine (MCV); 15% were varicella vaccine; and 4% were polio vaccine, 96% of which were the first dose. Excluding invalid doses resulted in a small change in vaccination coverage: 2.2% for DTP/DTaP, 0.7% for polio, 6.5% for hepatitis B, 1.4% for MCV, and 1.7% for varicella. The vaccine purchase cost to repeat at least one invalid dose ranged from approximately $10 million (public-purchased) to approximately $18 million (private-purchased). CONCLUSIONS: Nationally about 595,000 of children aged 19 to 35 months, born between February 1997 and May 1999, received at least one invalid dose of vaccine. The cost of revaccinating these children is substantial and may have a negative impact on parents, physicians, and vaccine purchasers. Educating immunization providers regarding proper immunization timing should be conducted to reduce the administration of invalid doses of vaccines.

Child, Preschool↗

Improving the immunization and health status of children in the Women, Infants, and Children (WIC) Program.

Maintaining enrollment in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and continued exposure of these children to immunization-promoting and nutritional benefits within the program is essential to improve the health status of this vulnerable population. Logistic regression was used to determine characteristics of 2 groups of children: those who dropped out of the program despite being eligible and those who remained in the program but were underimmunized. Of over 20,000 children 19-35 months old, 49% had participated in WIC but only 50% were still enrolled. Factors most strongly associated with dropping out of the program were older age of child; white, black, or American Indian race; living in an urban or suburban area; higher socioeconomic status but still eligible for the program; having only 1 child at home; and having mothers who were unmarried or less than 30 years old (p<0.05). Among current participants, factors most strongly associated with under-vaccination included younger age of the child; black or Asian race; moving from another state since birth; mother with less than a high-school education; and having 2 or more children under 18 years old living in the household (p<0.05). Routinely collected child/family information can be used to target outreach and immunization-promoting interventions toward children most likely to drop out of the program or to be underimmunized.

Aid to Families with Dependent Children↗

Children who have received no vaccines: who are they and where do they live?

CONTEXT: Each year 2.1 million children 19 to 35 months of age are undervaccinated. Among these are children who have received no vaccinations. Unvaccinated children are at increased risk of acquiring and transmitting vaccine-preventable diseases. OBJECTIVES: To assess whether the characteristics of children with no vaccinations differ from those of undervaccinated children, to monitor trends in the numbers of unvaccinated children, and to identify states with high rates and counties with large numbers of unvaccinated children. DESIGN: A nationally representative probability sample of children 19 to 35 months of age was collected annually between 1995 and 2001. Vaccination histories were ascertained from children's medical providers. Undervaccinated children had received > or =1 dose of diphtheria-tetanus-pertussis, polio, measles, Haemophilus influenzae type b, hepatitis B, or varicella vaccine but were not fully vaccinated. Unvaccinated children were children who were reported as having no medical providers and having received no vaccinations or children whose medical providers reported administering no vaccinations. PARTICIPANTS: A total of 151,720 children sampled between 1995 and 2001, 795 of whom were unvaccinated. RESULTS: Undervaccinated children tended to be black, to have a younger mother who was not married and did not have a college degree, to live in a household near the poverty level, and to live in a central city. Unvaccinated children tended to be white, to have a mother who was married and had a college degree, to live in a household with an annual income exceeding 75,000 dollars, and to have parents who expressed concerns regarding the safety of vaccines and indicated that medical doctors have little influence over vaccination decisions for their children. Unvaccinated children were more likely to be male than female. Annually, approximately 17,000 children were unvaccinated. The largest numbers of unvaccinated children lived in counties in California, Illinois, New York, Washington, Pennsylvania, Texas, Oklahoma, Colorado, Utah, and Michigan. States that allowed philosophical exemptions to laws mandating vaccinations for children as they entered school had significantly higher estimated rates of unvaccinated children. CONCLUSIONS: Unvaccinated children have characteristics that are distinctly different from those of undervaccinated children. Unvaccinated children are clustered geographically, increasing the risk of transmitting vaccine-preventable diseases to both unvaccinated and undervaccinated children.

Attitude to Health↗

Racial/ethnic disparities in preschool immunizations: United States, 1996-2001.

OBJECTIVES: We examined current racial/ethnic differences in immunization coverage rates among US preschool children. METHODS: Using National Immunization Survey data from 1996 through 2001, we compared vaccination coverage rates between non-Hispanic White, non-Hispanic Black, Hispanic, and Asian preschool children. RESULTS: During the 6-year study period, the immunization coverage gap between White and Black children widened by an average of 1.1% each year, and the gap between White and Hispanic children widened by an average of 0.5% each year. The gap between White and Asian children narrowed by an average of 0.8% each year. CONCLUSIONS: Racial/ethnic disparities in preschool immunization coverage rates have increased significantly among some groups; critical improvements in identifying, understanding, and addressing race/ethnicity-specific health care differences are needed to achieve the Healthy People 2010 goal of eliminating disparities.

Child, Preschool↗

Insurance status and vaccination coverage among US preschool children.

BACKGROUND: Insurance status has been shown to have an impact on children's use of preventive and acute health services. The objective of this study was to determine the relationship between insurance status and vaccination coverage among US preschool children aged 19 to 35 months. METHODS: We linked data from 2 national telephone surveys, the National Immunization Survey and the National Survey of Early Childhood Health, conducted during the first half of 2000. Children were considered up to date (UTD) when they had received at least 4 diphtheria-tetanus-acellular pertussis/diphtheria-tetanus-pertussis vaccines, 3 poliovirus vaccines, 1 MMR vaccine, 3 Haemophilus influenza vaccines, and 3 hepatitis B vaccines at the time the interview was conducted. RESULTS: Among the 735 children in our study sample, 72% were UTD. The vast majority (94%) reported some type of health insurance at the time of the survey. Children with private insurance were more likely to be UTD (80%) than those with public insurance (56%) or no insurance (64%). In a multivariate analysis that controlled for child's race/ethnicity; household income; maternal age/marital status/educational level; location of usual care; and Special Supplemental Nutrition Program for Women, Infants, and Children participation, insurance was no longer an independent predictor of vaccination. CONCLUSIONS: The disparity in vaccination coverage among publicly, privately, and uninsured children is dramatic, underscoring its importance as a marker for underimmunization, despite the multivariate findings. The Vaccines for Children Program, a partnership between public health and vaccination providers who serve uninsured children and those enrolled in Medicaid, is well suited to target and improve vaccination coverage among these vulnerable children.

Child, Preschool↗

Implementation and applications of bootstrap methods for the National Immunization Survey.

In complex probability sample surveys, numerous adjustments are customarily made to the survey weights to reduce potential bias in survey estimates. These adjustments include sampling design (SD) weight adjustments, which account for features of the sampling plan, and non-sampling design (NSD) weight adjustments, which account for non-sampling errors and other effects. Variance estimates prepared from complex survey data customarily account for SD weight adjustments, but rarely account for all NSD weight adjustments. As a result, variance estimates may be biased and standard confidence intervals may not achieve their nominal coverage levels. We describe the implementation of the bootstrap method to account for the SD and NSD weight adjustments for complex survey data. Using data from the National Immunization Survey (NIS), we illustrate the use of the bootstrap (i). for evaluating the use of standard confidence intervals that use Taylor series approximations to variance estimators that do not account for NSD weight adjustments, (ii). for obtaining confidence intervals for ranks estimated from weighted survey data, and (iii). for evaluating the predictive power of logistic regressions using receiver operating characteristic curve analyses that account for the SD and NSD adjustments made to the survey weights.

Analysis of Variance↗

Adjustments for non-telephone bias in random-digit-dialling surveys.

Telephone surveys are widely used in the U.S.A. for the study of health-related topics. They are subject to 'coverage bias' because they cannot sample households that do not have telephones. Although only around 5 per cent of households do not have a telephone, rates of telephone coverage show substantial variation by geography, demographic factors and socio-economic factors. In particular, lack of telephone service is more common among households that contain ethnic and racial minorities or that have lower socio-economic status with fewer opportunities for access to medical care and poorer health outcomes. Thus, failure to adequately account for households without telephones in health surveys may yield estimates of health outcomes that are misleading, particularly in states with at least moderate telephone non-coverage. The dynamic nature of the population of households without telephones offers a way of accounting for such households in telephone surveys. At any given time the population of telephone households includes households that have had a break or interruption in telephone service. Empirical results strongly suggest that these households are very similar to households that have never had telephone service. Thus, sampled households that report having had an interruption in telephone service may be used also to represent the portion of the population that has never had telephone service. This strategy can lead to a reduction in non-coverage bias in random-digit-dialling surveys. This paper presents two methods of adjusting for non-coverage of non-telephone households. The effectiveness of these methods is examined using data from the National Health Interview Survey. The interruption-in-telephone-service methods reduce non-coverage bias and can also result in a lower mean squared error. The application of the interruption-in-telephone-service methods to the National Immunization Survey is also discussed. This survey produces estimates for the 50 states and 28 urban areas. The interruption-in-telephone-service estimates tend be slightly lower than estimates resulting from poststratification and from another non-coverage adjustment method. The results suggest that the reduction in bias is greatest for variables that are highly correlated with the presence or absence of telephone service.

Bias↗