The utilization of therapuetic pharmaceutical agents by optometrists for the treatment of ocular disease

On April 18, 1989 Washington legislation legalized the use of therapeutic pharmaceutical agents by optometrists. It is now three years later, and therapeutic privileges have enabled optometrists to broaden the scope of optometry. This study summarizes the utilization of TPAs on 660 applications by TPA certified optometrists during the entire month of November 1992, in the state of Washington. Results of the study demonstrate the incidence of ocular diseases being effectively managed by optometrists. From this study, a practical list of therapeutical agents was generated,· to establish a drug of first choice in a clinical setting. Furthermore, it was shown that TPAs have allowed optometrists to treat 80% of ocular disease independently. The percentage of cases being referred and not treated was 11.06%. The percentage of ocular disease cases that were being co-managed was 9.85%. The percentage of ocular disease cases that were treated and referred was 7%. The optometric profile of a practice has a great influence on the amount of patients seen with ocular disease. The mode of practice consisting of group practice with one ophthalmologist had the highest amount of patients per practice but the lowest amount of hours per practice. The corporate practice saw the least number of ocular disease patients. The greater the number of ocular disease cases seen per practice the higher the income. The communities with a population size of less than 5,000 saw the highest number of ocular disease patients per practice and had the longest hours per practice

Concomitant diagnosis of immune deficiency and Pseudomonas sepsis in a 19 month old with ecthyma gangrenosum by host whole-genome sequencing.

X-linked agammaglobulinemia (XLA, OMIM#300300) is a rare monogenic primary immunodeficiency caused by mutations in the Bruton tyrosine kinase (BTK) gene. XLA is characterized by insufficient immunoglobulin levels and susceptibility to life-threatening bacterial infections. We report on a patient that presented with ecthyma gangrenosum and septicemia. Rapid trio whole-genome sequencing (rWGS) revealed an apparently de novo hemizygous pathogenic variant (c.726dupT; p.Ile243TyrfsTer15) in the BTK gene. Metagenomic analysis of rWGS sequences that did not align to the human genome revealed 770 aligned to the Pseudomonas aeruginosa PAO1 genome. The patient was diagnosed with XLA and pseudomonal sepsis

Actionable, Pathogenic Incidental Findings in 1,000 Participants’ Exomes

The incorporation of genomics into medicine is stimulating interest on the return of incidental findings (IFs) from exome and genome sequencing. However, no large-scale study has yet estimated the number of expected actionable findings per individual; therefore, we classified actionable pathogenic single-nucleotide variants in 500 European- and 500 African-descent participants randomly selected from the National Heart, Lung, and Blood Institute Exome Sequencing Project. The 1,000 individuals were screened for variants in 114 genes selected by an expert panel for their association with medically actionable genetic conditions possibly undiagnosed in adults. Among the 1,000 participants, 585 instances of 239 unique variants were identified as disease causing in the Human Gene Mutation Database (HGMD). The primary literature supporting the variants’ pathogenicity was reviewed. Of the identified IFs, only 16 unique autosomal-dominant variants in 17 individuals were assessed to be pathogenic or likely pathogenic, and one participant had two pathogenic variants for an autosomal-recessive disease. Furthermore, one pathogenic and four likely pathogenic variants not listed as disease causing in HGMD were identified. These data can provide an estimate of the frequency (∼3.4% for European descent and ∼1.2% for African descent) of the high-penetrance actionable pathogenic or likely pathogenic variants in adults. The 23 participants with pathogenic or likely pathogenic variants were disproportionately of European (17) versus African (6) descent. The process of classifying these variants underscores the need for a more comprehensive and diverse centralized resource to provide curated information on pathogenicity for clinical use to minimize health disparities in genomic medicine

Proton Beam Therapy for Large Hepatocellular Carcinoma

PurposeTo investigate the safety and efficacy of proton beam therapy (PBT) in patients with large hepatocellular carcinoma (HCC).Methods and MaterialsTwenty-two patients with HCC larger than 10 cm were treated with proton beam therapy at our institution between 1985 and 2006. Twenty-one of the 22 patients were not surgical candidates because of advanced HCC, intercurrent disease, or old age. Median tumor size was 11 cm (range, 10–14cm), and median clinical target volume was 567 cm3 (range, 335–1,398 cm3). Hepatocellular carcinoma was solitary in 18 patients and multifocal in 4 patients. Tumor types were nodular and diffuse in 18 and 4 patients, respectively. Portal vein tumor thrombosis was present in 11 patients. Median total dose delivered was 72.6 GyE in 22 fractions (range, 47.3–89.1 GyE in 10–35 fractions).ResultsThe median follow-up period was 13.4 months (range, 1.5–85 months). Tumor control rate at 2 years was 87%. One-year overall and progression-free survival rates were 64% and 62%, respectively. Two-year overall and progression-free survival rates were 36% and 24%, respectively. The predominant tumor progression pattern was new hepatic tumor development outside the irradiated field. No late treatment-related toxicity of Grade 3 or higher was observed.ConclusionsThe Bragg peak properties of PBT allow for improved conformality of the treatment field. As such, large tumor volumes can be irradiated to high doses without significant dose exposure to surrounding normal tissue. Proton beam therapy therefore represents a promising modality for the treatment of large-volume HCC. Our study shows that PBT is an effective and safe method for the treatment of patients with large HCC

Actionable exomic incidental findings in 6503 participants: challenges of variant classification

Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base

Response thresholds alone cannot explain empirical patterns of division of labor in social insects

The effects of heterogeneity in group composition remain a major hurdle to our understanding of collective behavior across disciplines. In social insects, division of labor (DOL) is an emergent, colony-level trait thought to depend on colony composition. Theoretically, behavioral response threshold models have most commonly been employed to investigate the impact of heterogeneity on DOL. However, empirical studies that systematically test their predictions are lacking because they require control over colony composition and the ability to monitor individual behavior in groups, both of which are challenging. Here, we employ automated behavioral tracking in 120 colonies of the clonal raider ant with unparalleled control over genetic, morphological, and demographic composition. We find that each of these sources of variation in colony composition generates a distinct pattern of behavioral organization, ranging from the amplification to the dampening of inherent behavioral differences in heterogeneous colonies. Furthermore, larvae modulate interactions between adults, exacerbating the apparent complexity. Models based on threshold variation alone only partially recapitulate these empirical patterns. However, by incorporating the potential for variability in task efficiency among adults and task demand among larvae, we account for all the observed phenomena. Our findings highlight the significance of previously overlooked parameters pertaining to both larvae and workers, allow the formulation of theoretical predictions for increasing colony complexity, and suggest new avenues of empirical study.ISSN:1544-9173ISSN:1545-788

Emergent behavioral organization in heterogeneous groups of a social insect

The composition of social groups has profound effects on their function, from collective decision-making to foraging efficiency. But few social systems afford sufficient control over group composition to precisely quantify its effects on individual and collective behavior. Here we combine experimental and theoretical approaches to study the effect of group composition on individual behavior and division of labor (DOL) in a social insect. Experimentally, we use automated behavioral tracking to monitor 120 colonies of the clonal raider ant, Ooceraea biroi, with controlled variation in three key correlates of social insect behavior: genotype, age, and morphology. We find that each of these sources of heterogeneity generates a distinct pattern of behavioral organization, including the amplification or dampening of inherent behavioral differences in colonies with mixed types. Theoretically, we use a well-studied model of DOL to explore potential mechanisms underlying the experimental findings. We find that the simplest implementation of this model, which assumes that heterogeneous individuals differ only in response thresholds, could only partially recapitulate the empirically observed patterns of behavior. However, the full spectrum of observed phenomena was recapitulated by extending the model to incorporate two factors that are biologically meaningful but theoretically rarely considered: variation among workers in task performance efficiency and among larvae in task demand. Our results thus show that different sources of heterogeneity within social groups can generate different, sometimes non-intuitive, behavioral effects, but that relatively simple models can capture these dynamics and thereby begin to elucidate the basic organizational principles of DOL in social insects