scholarly journals The impact of Fishers Reproductive Compensation on raising equilibrium frequencies of semi-dominant, non-lethal mutations under mutation/selection balance.

2021 ◽  
Author(s):  
Ian M Hastings

Fishers reproductive compensation (fRC) occurs when a species demography means the death of an individual allows increased survival of his/her relatives, usually assumed to be full sibs. This likely occurs in many species, including humans. Several important recessive human genetic diseases cause early foetal/infant death allowing fRC to act on these mutations. The impact of fRC on these genetic conditions has been calculated and shown to be substantial as quantified by w, the fold increase in equilibrium frequencies of the mutation under fRC compared to its absence i.e. w=1.22 and w =1.33 for autosomal and sex-linked loci, respectively. However, the impact of fRC on the frequency of the much large class of semi-dominant, non-lethal mutations is unknown. This is calculated here by a mixture of simulation and algebra and shown that w is approximately 2-h*s and 2-0.19s-0.85h*s for autosomal and sex-linked loci respectively where h is dominance (varied between 0.05 and 0.95) and s is selection coefficient (varied between 0.05 and 0.9). These results show that the actions of fRC can almost double equilibrium frequency of mutations with low values of h and/or s. The dynamics of fRC acting on this type of mutation are also identified and discussed.

2020 ◽  
Vol 12 ◽  
Author(s):  
Sai Akilesh M ◽  
Ashish Wadhwani

: Infectious diseases have been prevalent since many decades and viral pathogens have caused global health crisis and economic meltdown on a devastating scale. High occurrence of newer viral infections in the recent years, in spite of the progress achieved in the field of pharmaceutical sciences defines the critical need for newer and more effective antiviral therapies and diagnostics. The incidence of multi-drug resistance and adverse effects due to the prolonged use of anti-viral therapy is also a major concern. Nanotechnology offers a cutting edge platform for the development of novel compounds and formulations for biomedical applications. The unique properties of nano-based materials can be attributed to the multi-fold increase in the surface to volume ratio at the nano-scale, tunable surface properties of charge and chemical moieties. Idealistic pharmaceutical properties such as increased bioavailability and retention times, lower toxicity profiles, sustained release formulations, lower dosage forms and most importantly, targeted drug delivery can be achieved through the approach of nanotechnology. The extensively researched nano-based materials are metal and polymeric nanoparticles, dendrimers and micelles, nano-drug delivery vesicles, liposomes and lipid based nanoparticles. In this review article, the impact of nanotechnology on the treatment of Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus (HSV) viral infections during the last decade are outlined.


2020 ◽  
Vol 41 (S1) ◽  
pp. s111-s112
Author(s):  
Mohammed Alsuhaibani ◽  
Mohammed Alzunitan ◽  
Kyle Jenn ◽  
Daniel Diekema ◽  
Michael Edmond ◽  
...  

Background: Surveillance for surgical site infections (SSI) is recommended by the CDC. Currently, colon and abdominal hysterectomy SSI rates are publicly available and impact hospital reimbursement. However, the CDC NHSN allows surgical procedures to be abstracted based on International Classification of Diseases, Tenth Revision (ICD-10) or current procedural terminology (CPT) codes. We assessed the impact of using ICD and/or CPT codes on the number of cases abstracted and SSI rates. Methods: We retrieved administrative codes (ICD and/or CPT) for procedures performed at the University of Iowa Hospitals & Clinics over 1 year: October 2018–September 2019. We included 10 procedure types: colon, hysterectomy, cesarean section, breast, cardiac, craniotomy, spinal fusion, laminectomy, hip prosthesis, and knee prosthesis surgeries. We then calculated the number of procedures that would be abstracted if we used different permutations in administration codes: (1) ICD codes only, (2) CPT codes only, (3) both ICD and CPT codes, and (4) at least 1 code from either ICD or CPT. We then calculated the impact on SSI rates based on any of the 4 coding permutations. Results: In total, 9,583 surgical procedures and 180 SSIs were detected during the study period using the fourth method (ICD or CPT codes). Denominators varied according to procedure type and coding method used. The number of procedures abstracted for breast surgery had a >10-fold difference if reported based on ICD only versus ICD or CPT codes (104 vs 1,109). Hip prosthesis had the lowest variation (638 vs 767). For SSI rates, cesarean section showed almost a 3-fold increment (2.6% when using ICD only to 7.32% with both ICD & CPT), whereas abdominal hysterectomy showed nearly a 2-fold increase (1.14% when using CPT only to 2.22% with both ICD & CPT codes). However, SSI rates remained fairly similar for craniotomy (0.14% absolute difference), hip prosthesis (0.24% absolute difference), and colon (0.09% absolute difference) despite differences in the number of abstracted procedures and coding methods. Conclusions: Denominators and SSI rates vary depending on the coding method used. Variations in the number of procedures abstracted and their subsequent impact on SSI rates were not predictable. Variations in coding methods used by hospitals could impact interhospital comparisons and benchmarking, potentially leading to disparities in public reporting and hospital penalties.Funding: NoneDisclosures: None


2021 ◽  
Vol 14 (5) ◽  
pp. 453
Author(s):  
Gabriela Wiergowska ◽  
Dominika Ludowicz ◽  
Kamil Wdowiak ◽  
Andrzej Miklaszewski ◽  
Kornelia Lewandowska ◽  
...  

To improve physicochemical properties of vardenafil hydrochloride (VAR), its amorphous form and combinations with excipients—hydroxypropyl methylcellulose (HPMC) and β-cyclodextrin (β-CD)—were prepared. The impact of the modification on physicochemical properties was estimated by comparing amorphous mixtures of VAR to their crystalline form. The amorphous form of VAR was obtained as a result of the freeze-drying process. Confirmation of the identity of the amorphous dispersion of VAR was obtained through the use of comprehensive analysis techniques—X-ray powder diffraction (PXRD) and differential scanning calorimetry (DSC), supported by FT-IR (Fourier-transform infrared spectroscopy) coupled with density functional theory (DFT) calculations. The amorphous mixtures of VAR increased its apparent solubility compared to the crystalline form. Moreover, a nearly 1.3-fold increase of amorphous VAR permeability through membranes simulating gastrointestinal epithelium as a consequence of the changes of apparent solubility (Papp crystalline VAR = 6.83 × 10−6 cm/s vs. Papp amorphous VAR = 8.75 × 10−6 cm/s) was observed, especially for its combinations with β-CD in the ratio of 1:5—more than 1.5-fold increase (Papp amorphous VAR = 8.75 × 10−6 cm/s vs. Papp amorphous VAR:β-CD 1:5 = 13.43 × 10−6 cm/s). The stability of the amorphous VAR was confirmed for 7 months. The HPMC and β-CD are effective modifiers of its apparent solubility and permeation through membranes simulating gastrointestinal epithelium, suggesting a possibility of a stronger pharmacological effect.


Author(s):  
Carolyn R. Ahlers-Schmidt ◽  
Christy Schunn ◽  
Ashley M. Hervey ◽  
Maria Torres ◽  
Cherie Sage ◽  
...  

Sleep-related infant deaths, including Sudden Infant Death Syndrome (SIDS), are the number one cause of death in infants between 28 days and one year of life. Nearly half of families experiencing a sleep-related infant death in Kansas were involved with the Department of Children and Families Child Protective Services (CPS), making CPS staff a priority for safe sleep training. This study assessed the impact of the two-day Kansas Infant Death and SIDS (KIDS) Network Safe Sleep Instructor (SSI) train-the-trainer program on CPS staffs’ knowledge of the American Academy of Pediatrics safe sleep recommendations. Training was attended by 43 participants, 27 (63%) of whom were employed by CPS. CPS staff had significantly lower baseline knowledge on the 10-item pretest (t = 3.33, p = 0.002), but both CPS and other attendees showed significant improvement by posttest (t = 8.53, p < 0.001 and t = 4.44, p < 0.001, respectively). Following SSI certification, CPS SSIs provided more safe sleep training to professionals than other SSIs (1051 vs. 165, respectively), and both groups of SSIs were able to significantly increase the knowledge of their trainees. Overall, the KIDS Network SSI training was successful. The innovative partnership with CPS allowed for provision of training to a group not historically targeted for safe sleep education.


Author(s):  
Marta Oliveira ◽  
Sílvia Capelas ◽  
Cristina Delerue-Matos ◽  
Simone Morais

Grilling activities release large amounts of hazardous pollutants, but information on restaurant grill workers’ exposure to polycyclic aromatic hydrocarbons (PAHs) is almost inexistent. This study assessed the impact of grilling emissions on total workers’ exposure to PAHs by evaluating the concentrations of six urinary biomarkers of exposure (OHPAHs): naphthalene, acenaphthene, fluorene, phenanthrene, pyrene, and benzo(a)pyrene. Individual levels and excretion profiles of urinary OHPAHs were determined during working and nonworking periods. Urinary OHPAHs were quantified by high-performance liquid-chromatography with fluorescence detection. Levels of total OHPAHs (∑OHPAHs) were significantly increased (about nine times; p ≤ 0.001) during working comparatively with nonworking days. Urinary 1-hydroxynaphthalene + 1-hydroxyacenapthene and 2-hydroxyfluorene presented the highest increments (ca. 23- and 6-fold increase, respectively), followed by 1-hydroxyphenanthrene (ca. 2.3 times) and 1-hydroxypyrene (ca. 1.8 times). Additionally, 1-hydroxypyrene levels were higher than the benchmark, 0.5 µmol/mol creatinine, in 5% of exposed workers. Moreover, 3-hydroxybenzo(a)pyrene, biomarker of exposure to carcinogenic PAHs, was detected in 13% of exposed workers. Individual excretion profiles showed a cumulative increase in ∑OHPAHs during consecutive working days. A principal component analysis model partially discriminated workers’ exposure during working and nonworking periods showing the impact of grilling activities. Urinary OHPAHs were increased in grill workers during working days.


2015 ◽  
Vol 17 (01) ◽  
pp. 1550003 ◽  
Author(s):  
FRANK VANCLAY

Over 150 forms of impact assessment can be identified using Google searches, with several new forms appearing since 2003. Since then, the popularity of the various members of the impact assessment family has changed, partly in response to legislative and regulatory changes, and general trends in society. The information explosion and expansion of the internet has resulted in a 32 fold increase in the number of hits for "impact assessment", now over 12 million. The conventional methods most frequently mentioned in 2003 had relatively low proportional change over the last 10 years but remain amongst the most frequently mentioned in 2014: risk assessment, public participation, cost-benefit analysis, public involvement, environmental monitoring, and project evaluation. The terms with highest proportional change (i.e. the super-hot topics) were primarily social concerns, including: equality impact assessment, welfare impact assessment, mental health impact assessment, disability impact assessment, human impact assessment, social impact assessment, and social risk assessment. Other terms that had high proportional change included life cycle impact assessment. Information about the relative popularity of the various forms of impact assessment is used in this paper to discuss issues and trends in the broad field of impact assessment.


2014 ◽  
Vol 598 ◽  
pp. 141-146
Author(s):  
Adam Lipski ◽  
Zbigniew Lis

The aim of this paper is to assess the impact of the rivet hole sizing process on the fatigue life based on the example of the structural connections characteristic for riveted joints used in aviation industry. Test specimens reflected the structural connection consisting in a riveted lap joint of an airplane plating stiffened with a T-bar. Connected plates and the T-bar are made of D16CzATW aluminum alloy. 3 mm diameter oval head solid rivets for aviation-related purposes were made of PA24 aluminum. During fatigue tests, individual specimens with non-sized holes and with sized holes were subjected to uniaxial, one-sided, fixed-amplitude loading (R = 0). It can be concluded from the fatigue life comparison that introduction of an additional operation in the riveting process, i.e. the hole sizing, results in significant, about two-fold increase of the fatigue life of the riveted structural connection, even at slight sizing degree. The difference of the specimen damage nature was observed between specimens with sized and non-sized holes.


2018 ◽  
Vol 219 (9) ◽  
pp. 1499-1509 ◽  
Author(s):  
Victor Chaumeau ◽  
Ladda Kajeechiwa ◽  
Bénédicte Fustec ◽  
Jordi Landier ◽  
Saw Naw Nyo ◽  
...  

Abstract Background The objective of mass antimalarial drug administration (MDA) is to eliminate malaria rapidly by eliminating the asymptomatic malaria parasite reservoirs and interrupting transmission. In the Greater Mekong Subregion, where artemisinin-resistant Plasmodium falciparum is now widespread, MDA has been proposed as an elimination accelerator, but the contribution of asymptomatic infections to malaria transmission has been questioned. The impact of MDA on entomological indices has not been characterized previously. Methods MDA was conducted in 4 villages in Kayin State (Myanmar). Malaria mosquito vectors were captured 3 months before, during, and 3 months after MDA, and their Plasmodium infections were detected by polymerase chain reaction (PCR) analysis. The relationship between the entomological inoculation rate, the malaria prevalence in humans determined by ultrasensitive PCR, and MDA was characterized by generalized estimating equation regression. Results Asymptomatic P. falciparum and Plasmodium vivax infections were cleared by MDA. The P. vivax entomological inoculation rate was reduced by 12.5-fold (95% confidence interval [CI], 1.6–100-fold), but the reservoir of asymptomatic P. vivax infections was reconstituted within 3 months, presumably because of relapses. This was coincident with a 5.3-fold (95% CI, 4.8–6.0-fold) increase in the vector infection rate. Conclusion Asymptomatic infections are a major source of malaria transmission in Southeast Asia.


Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Shih-Chieh Chien ◽  
Chien-Yi Hsu ◽  
Hung-Yi Liu ◽  
Chao-Feng Lin ◽  
Chung-Lieh Hung ◽  
...  

Abstract Background This study investigated temporal trends in the treatment and mortality of patients with cardiogenic shock (CS) in Taiwan in relation to acute myocardial infarction (AMI) accreditation implemented in 2009 and the unavailability of percutaneous ventricular assist devices. Methods Data of patients diagnosed as having CS between January 2003 and December 2017 were collected from Taiwan’s National Health Insurance Research Database. Each case was followed from the date of emergency department arrival or hospital admission for the first incident associated with a CS diagnosis up to a 1-year interval. Measurements included demographics, comorbidities, treatment, mortality, and medical costs. Using an interrupted time-series (ITS) design with multi-level mixed-effects logistic regression model, we assessed the impact of AMI accreditation implementation on the mortality of patients with AMI and CS overall and stratified by the hospital levels. Results In total, 64 049 patients with CS (mean age:70 years; 62% men) were identified. The incidence rate per 105 person-years increased from 17 in 2003 to 25 in 2010 and plateaued thereafter. Average inpatient costs increased from 159 125 points in 2003 to 240 993 points in 2017, indicating a 1.5-fold increase. The intra-aortic balloon pump application rate was approximately 22–25% after 2010 (p = 0.093). Overall, in-hospital, 30-day, and 1-year mortality declined from 60.3%, 63.0%, and 69.3% in 2003 to 47.9%, 50.8% and 59.8% in 2017, respectively. The decline in mortality was more apparent in patients with AMI-CS than in patients with non-AMI-CS. The ITS estimation revealed a 2% lower in-hospital mortality in patients with AMI-CS treated in district hospitals after the AMI accreditation had been implemented for 2 years. Conclusions In Taiwan, the burden of CS has consistently increased due to high patient complexity, advanced therapies, and stable incidence. Mortality declined over time, particularly in patients with AMI-CS, which may be attributable to advancements in AMI therapies and this quality-improving policy.


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