The National Medical Association’s Call For Responsibility During the Progressive Era: The Duty of Black Physicians to Improve Conditions in Black Communities to Combat Tuberculosis Mortality Rates.

The National Medical Association (NMA) was founded in 1895 after the American Medical Association denied a group of black physicians membership. Black physicians used this organization as a platform to launch a three-tiered approach to combating the tuberculosis epidemic: debunking popular beliefs of black biological inferiority, proactive education of the black community on proper hygiene and behavior, and lobbying to gain support from social reforms and campaigns by targeting white anxieties and morals. The NMA identified the causes of high death rates among black populations from tuberculosis as environmental, economic and social conditions. They placed the primary responsibility of changing these conditions and improving health on black physicians rather than depending solely on white run social reforms and aid. In order to improve the conditions and health of blacks, the NMA encouraged black physicians to educate the black community about tuberculosis causes, prevention and treatment. As tuberculosis mortality rates in black communities held constant, the NMA realized they needed the support of established social reform movements to effectively combat the disease. Many Progressive Era social reform movements improved environmental and economic conditions for whites but often excluded black communities. Whites dominated the Anti-Tuberculosis Movement’s campaigns and usually excluded blacks from the aid they provided to tuberculosis patients. The NMA in turn played off of white anxieties concerning contamination and moral obligation in order to gain resources to improve black conditions. The NMA felt that black physicians’ held the responsibility to educate the public and gain support from previously racially exclusive social movements

Variation in ampicillin dosing for lower respiratory tract infections and neonatal bacterial infections in US children\u27s hospitals

OBJECTIVE: We examined ampicillin dosing in pediatric patients across 3 conditions: (1) bacterial lower respiratory tract infections (LRTIs) in infants and children \u3e3 months, (2) neonates with suspected or proven sepsis, and (3) neonates with suspected central nervous system (CNS) infections. We compared our findings to dosing guidance for these specific indications. DESIGN: Retrospective cohort study. SETTING: The study included data from 32 children\u27s hospitals in the United States. METHODS: We reviewed prescriptions from the SHARPS study of antimicrobials, a survey of antibiotic prescribing from July 2016 to December 2017. Prescriptions were analyzed for indication, total daily dose per kilogram, and presence of antimicrobial stewardship program (ASP) review. LRTI prescriptions were compared to IDSA recommendations for community-acquired pneumonia. Neonatal prescriptions were compared to recommendations from the American Academy of Pediatrics (AAP). Prescriptions were categorized as optimal (80%-120% of recommended dosing), suboptimal (\u3c80% of recommended dosing), or excessive (\u3e120% of recommended dosing). RESULTS: Among 1,038 ampicillin prescriptions, we analyzed 88 prescriptions for LRTI, 499 prescriptions for neonatal sepsis, and 27 prescriptions for neonatal CNS infection. Of the LRTI prescriptions, 77.3%were optimal. Of prescriptions for neonatal sepsis, 81.6% were excessive compared to AAP bacteremia recommendations but 78.8% were suboptimal compared to AAP meningitis guidelines. Also, 48.1% of prescriptions for neonatal CNS infection were suboptimal, and 50.6% of prescriptions were not reviewed by the ASP. CONCLUSIONS: LRTI dosing is generally within the IDSA-recommended range. However, dosing for neonatal sepsis often exceeds the recommendation for bacteremia but is below the recommendation for meningitis. This variability points to an important opportunity for future antimicrobial stewardship efforts

Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: An economic evaluation alongside a randomised controlled trial

Objective: To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device ('LNG-IUS') and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. Methods: 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov) model with a 24 month follow-up. The model structure was informed by the trial women's pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY) estimated using both EQ-5D and SF-6D. Results: Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100) and generated 0.002 more QALYs. Conclusion: Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most costeffective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial. Copyright: © 2014 Sanghera et al

Signs of a vector's adaptive choice: on the evasion of infectious hosts and parasite-induced mortality

Laboratory and field experiments have demonstrated in many cases that malaria vectors do not feed randomly, but show important preferences either for infected or non-infected hosts. These preferences are likely in part shaped by the costs imposed by the parasites on both their vertebrate and dipteran hosts. However, the effect of changes in vector behaviour on actual parasite transmission remains a debated issue. We used the natural associations between a malaria-like parasite Polychromophilus murinus, the bat fly Nycteribia kolenatii and a vertebrate host the Daubenton's bat Myotis daubentonii to test the vector's feeding preference based on the host's infection status using two different approaches: 1) controlled behavioural assays in the laboratory where bat flies could choose between a pair of hosts; 2) natural bat fly abundance data from wild-caught bats, serving as an approximation of realised feeding preference of the bat flies. Hosts with the fewest infectious stages of the parasite were most attractive to the bat flies that did switch in the behavioural assay. In line with the hypothesis of costs imposed by parasites on their vectors, bat flies carrying parasites had higher mortality. However, in wild populations, bat flies were found feeding more based on the bat's body condition, rather than its infection level. Though the absolute frequency of host switches performed by the bat flies during the assays was low, in the context of potential parasite transmission they were extremely high. The decreased survival of infected bat flies suggests that the preference for less infected hosts is an adaptive trait. Nonetheless, other ecological processes ultimately determine the vector's biting rate and thus transmission. Inherent vector preferences therefore play only a marginal role in parasite transmission in the field. The ecological processes rather than preferences per se need to be identified for successful epidemiological predictions

Optimisation of pharmacy content in clinical cancer research protocols: Experience of the United Kingdom Chemotherapy and Pharmacy Advisory Service

Background: Clarity and accuracy of the pharmacy aspects of cancer clinical trial protocols is essential. Inconsistencies and ambiguities in such protocols have the potential to delay research and jeopardise both patient safety and collection of credible data. The Chemotherapy and Pharmacy Advisory Service was established by the UK National Cancer Research Network, currently known as National Institute for Health Research Clinical Research Network, to improve the quality of pharmacy-related content in cancer clinical research protocols. This article reports the scope of Chemotherapy and Pharmacy Advisory Service, its methodology of mandated protocol review and pharmacy-related guidance initiatives and its current impact. Methods: Over a 6-year period (2008–2013) since the inception of Chemotherapy and Pharmacy Advisory Service, cancer clinical trial protocols were reviewed by the service, prior to implementation at clinical trial sites. A customised Review Checklist was developed and used by a panel of experts to standardise the review process and report back queries and inconsistencies to chief investigators. Based on common queries, a Standard Protocol Template comprising specific guidance on drug-related content and a Pharmacy Manual Template were developed. In addition, a guidance framework was established to address ‘ad hoc’ pharmacy-related queries. The most common remarks made at protocol review have been summarised and categorised through retrospective analysis. In order to evaluate the impact of the service, chief investigators were asked to respond to queries made at protocol review and make appropriate changes to their protocols. Responses from chief investigators have been collated and acceptance rates determined. Results: A total of 176 protocols were reviewed. The median number of remarks per protocol was 26, of which 20 were deemed clinically relevant and mainly concerned the drug regimen, support medication, frequency and type of monitoring and drug supply aspects. Further analysis revealed that 62% of chief investigators responded to the review. All responses were positive with an overall acceptance rate of 89% of the proposed protocol changes. Conclusion: Review of pharmacy content of cancer clinical trial protocols is feasible and exposes many undetected clinically relevant issues that could hinder efficient trial conduct. Our service audit revealed that the majority of suggestions were effectively incorporated in the final protocols. The refinement of existing and development of new pharmacy-related guidance documents by Chemotherapy and Pharmacy Advisory Service might aid in better and safer clinical research

Ultrasonographic risk stratification of indeterminate thyroid nodules; a comparison of an artificial intelligence algorithm with radiologist performance

Background, Motivation and Objective: Thyroid nodules with indeterminate or suspicious cytology are commonly encountered in clinical practice and their clinical management is controversial. Recently, genetical analysis of thyroid fine needle aspiration (FNAs) was implemented at some institutions to differentiate thyroid nodules as high and low risk based on the presence of certain oncogenes commonly associated with aggressive tumor behavior and poor patient outcomes. Our group recently detailed the performance of a machine-learning model based on ultrasonography images of thyroid nodules for the prediction of high and low risk mutations. This study evaluated the performance of a second-generation machine-learning algorithm incorporating both object detection analysis and image classification and subsequently compared performance against blinded radiologists. Statement of Contribution/Methods: This retrospective study was conducted at Thomas Jefferson University and included an evaluation of 262 thyroid nodules that underwent ultrasound imaging, ultrasound-guided FNA and next-generation sequencing (NGS) or surgical pathology after resection. An object detection and image classification model were employed to first identify the location of nodules and then to assess the malignancy. A Google cloud platform (AutoML Vision; Google LLC) was used for this purpose. Either NGS or surgical pathology was considered as reference standard upon availability. 211 nodules were used for model development and the unused 51 nodules for model testing. Diagnostic performance in 47 nodules for which pathology or NGS were available was compared to blinded reads by 3 radiologists and performance expressed as mean ± standard deviation %. Results/Discussion: The algorithm achieved positive predictive value (PPV) of 68.31% and sensitivity of 86.81% within the training model. The model was tested on images of 51 unused nodules and all 51 nodules were correctly located (100%). For risk stratification, the model demonstrated a sensitivity of 73.9%, specificity of 70.8%, positive predictive value (PPV) of 70.8%, negative predictive value (NPV) of 73.9% and overall accuracy of 66.7% in the 47 nodules. For comparison, the 3 radiologist performance in this same dataset demonstrated a sensitivity of, specificity of, PPV of, NPV of, and overall accuracy of This work demonstrates that a machine-learning algorithm using image classification performed similarly, if not slightly better than 3 experienced radiologists. Future research will focus on incorporating machine learning findings within radiologist interpretation to potentially improve diagnostic accuracy

Incorporation of a Machine Learning Algorithm With Object Detection Within the Thyroid Imaging Reporting and Data System Improves the Diagnosis of Genetic Risk.

Background: The role of next generation sequencing (NGS) for identifying high risk mutations in thyroid nodules following fine needle aspiration (FNA) biopsy continues to grow. However, ultrasound diagnosis even using the American College of Radiology\u27s Thyroid Imaging Reporting and Data System (TI-RADS) has limited ability to stratify genetic risk. The purpose of this study was to incorporate an artificial intelligence (AI) algorithm of thyroid ultrasound with object detection within the TI-RADS scoring system to improve prediction of genetic risk in these nodules. Methods: Two hundred fifty-two nodules from 249 patients that underwent ultrasound imaging and ultrasound-guided FNA with NGS with or without resection were retrospectively selected for this study. A machine learning program (Google AutoML) was employed for both automated nodule identification and risk stratification. Two hundred one nodules were used for model training and 51 reserved for testing. Three blinded radiologists scored the images of the test set nodules using TI-RADS and assigned each nodule as high or low risk based on the presence of highly suspicious imaging features on TI-RADS (very hypoechoic, taller-than-wide, extra-thyroidal extension, punctate echogenic foci). Subsequently, the TI-RADS classification was modified to incorporate AI for T4 nodules while treating T1-3 as low risk and T5 as high risk. All diagnostic predictions were compared to the presence of a high-risk mutation and pathology when available. Results: The AI algorithm correctly located all nodules in the test dataset (100% object detection). The model predicted the malignancy risk with a sensitivity of 73.9%, specificity of 70.8%, positive predictive value (PPV) of 70.8%, negative predictive value (NPV) of 73.9% and accuracy of 72.4% during the testing. The radiologists performed with a sensitivity of 52.1 ± 4.4%, specificity of 65.2 ± 6.4%, PPV of 59.1 ± 3.5%, NPV of 58.7 ± 1.8%, and accuracy of 58.8 ± 2.5% when using TI-RADS and sensitivity of 53.6 ± 17.6% (p=0.87), specificity of 83.3 ± 7.2% (p=0.06), PPV of 75.7 ± 8.5% (p=0.13), NPV of 66.0 ± 8.8% (p=0.31), and accuracy of 68.7 ± 7.4% (p=0.21) when using AI-modified TI-RADS. Conclusions: Incorporation of AI into TI-RADS improved radiologist performance and showed better malignancy risk prediction than AI alone when classifying thyroid nodules. Employing AI in existing thyroid nodule classification systems may help more accurately identifying high-risk nodules

Stakeholders' Participation in Planning and Priority Setting in the Context of a Decentralised Health Care system: the case of prevention of mother to child Transmission of HIV Programme in Tanzania.

In Tanzania, decentralisation processes and reforms in the health sector aimed at improving planning and accountability in the sector. As a result, districts were given authority to undertake local planning and set priorities as well as allocate resources fairly to promote the health of a population with varied needs. Nevertheless, priority setting in the health care service has remained a challenge. The study assessed the priority setting processes in the planning of the prevention of mother to child transmission of HIV (PMTCT) programme at the district level in Tanzania. This qualitative study was conducted in Mbarali district, south-western Tanzania. The study applied in-depth interviews and focus group discussions in the data collection. Informants included members of the Council Health Management Team, regional PMTCT managers and health facility providers. Two plans were reported where PMTCT activities could be accommodated; the Comprehensive Council Health Plan and the Regional PMTCT Plan that was donor funded. As donors had their own globally defined priorities, it proved difficult for district and regional managers to accommodate locally defined PMTCT priorities in these plans. As a result few of these were funded. Guidelines and main priority areas of the Ministry of Health and Social Welfare (MoHSW) also impacted on the ability of the districts and regions to act, undermining the effectiveness of the decentralisation policy in the health sector. The challenges in the priority setting processes revealed within the PMTCT initiative indicate substantial weaknesses in implementing the Tanzania decentralisation policy. There is an urgent need to revive the strategies and aims of the decentralisation policy at all levels of the health care system with a view to improving health service delivery

Lethal iron deprivation induced by non-neutralizing antibodies targeting transferrin receptor 1 in malignant B cells

A number of antibodies have been developed that induce lethal iron deprivation (LID) by targeting the transferrin receptor 1 (TfR1/CD71) and either neutralizing transferrin (Tf) binding, blocking internalization of the receptor and/or inducing its degradation. We have developed recombinant antibodies targeting human TfR1 (ch128.1 and ch128.1Av), which induce receptor degradation and are cytotoxic to certain malignant B-cells. We now show that internalization of TfR1 bound to these antibodies can lead to its sequestration and degradation, as well as reduced Tf uptake, and the induction of a transcriptional response consistent with iron deprivation, which is mediated in part by downstream targets of p53. Cells resistant to these antibodies do not sequester and degrade TfR1 after internalization of the antibody/receptor complex, and accordingly maintain their ability to internalize Tf. These findings are expected to facilitate the rational design and clinical use of therapeutic agents targeting iron import via TfR1 in hematopoietic malignancies.Fil: Rodríguez, José A.. University of California at Los Angeles; Estados UnidosFil: Luria Pérez, Rosendo. University of California at Los Angeles; Estados Unidos. Hospital infantil de México “Federico Gómez”; MéxicoFil: López Valdés, Héctor E.. University of California at Los Angeles; Estados UnidosFil: Casero, David. University of California at Los Angeles; Estados UnidosFil: Daniels, Tracy R.. University of California at Los Angeles; Estados UnidosFil: Patel, Shabnum. University of California at Los Angeles; Estados UnidosFil: Avila, David. University of California at Los Angeles; Estados UnidosFil: Leuchter, Richard. University of California at Los Angeles; Estados UnidosFil: So, Sokuntheavy. University of California at Los Angeles; Estados UnidosFil: Ortiz Sánchez, Elizabeth. University of California at Los Angeles; Estados UnidosFil: Bonavida, Benjamin. University of California at Los Angeles; Estados UnidosFil: Martínez Maza, Otoniel. University of California at Los Angeles; Estados UnidosFil: Charles, Andrew C.. University of California at Los Angeles; Estados UnidosFil: Pellegrini, Matteo. University of California at Los Angeles; Estados UnidosFil: Helguera, Gustavo Fernando. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Penichet, Manuel L.. University of California at Los Angeles; Estados Unido

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap