Natural Forest Regeneration Algorithm for Optimum Design of Truss Structures with Continuous and Discrete Variables

In  this  paper  the  recently  developed  nature  inspired  metaheuristic algorithm is utilized for optimum design of truss structures with continuous and discrete variables.  This algorithm is inspired  by  the  natural  process  happening  in  the  forests  with the  rapidly  change  of  environment  and  their  natural  regeneration.   Based  on  this  process  a  simple  powerful  optimization technique is introduced so-called Natural Forest Regeneration (NFR).  Some  well-studied  benchmark  structural  problems  are investigated with both continuous and discrete sizing variables and the results of the NRF are compared to those of some previously developed algorithms

A Biallelic Frameshift Indel in PPP1R35 as a Cause of Primary Microcephaly

Protein phosphatase 1 regulatory subunit 35 (PPP1R35) encodes a centrosomal protein required for recruiting microtubule-binding elongation machinery. Several proteins in this centriole biogenesis pathway correspond to established primary microcephaly (MCPH) genes, and multiple model organism studies hypothesize PPP1R35 as a candidate MCPH gene. Here, using exome sequencing (ES) and family-based rare variant analyses, we report a homozygous, frameshifting indel deleting the canonical stop codon in the last exon of PPP1R35 [Chr7: c.753_*3delGGAAGCGTAGACCinsCG (p.Trp251Cysfs*22)]; the variant allele maps in a 3.7 Mb block of absence of heterozygosity (AOH) in a proband with severe MCPH (-4.3 SD at birth, -6.1 SD by 42 months), pachygyria, and global developmental delay from a consanguineous Turkish kindred. Droplet digital PCR (ddPCR) confirmed mutant mRNA expression in fibroblasts. In silico prediction of the translation of mutant PPP1R35 is expected to be elongated by 18 amino acids before encountering a downstream stop codon. This complex indel allele is absent in public databases (ClinVar, gnomAD, ARIC, 1000 genomes) and our in-house database of 14,000+ exomes including 1800+ Turkish exomes supporting predicted pathogenicity. Comprehensive literature searches for PPP1R35 variants yielded two probands affected with severe microcephaly (-15 SD and -12 SD) with the same homozygous indel from a single, consanguineous, Iranian family from a cohort of 404 predominantly Iranian families. The lack of heterozygous cases in two large cohorts representative of the genetic background of these two families decreased our suspicion of a founder allele and supports the contention of a recurrent mutation. We propose two potential secondary structure mutagenesis models for the origin of this variant allele mediated by hairpin formation between complementary GC rich segments flanking the stop codon via secondary structure mutagenesis

The impact of rural health system reform on hospitalization rates in the Islamic Republic of Iran: an interrupted time series

OBJECTIVE: To assess the effects on hospital utilization rates of a major health system reform – a family physician programme and a social protection scheme – undertaken in rural areas of the Islamic Republic of Iran in 2005. METHODS: A “tracer” province that was not a patient referral hub was selected for the collection of monthly hospitalization data over a period of about 10 years, beginning two years before the rural health system reform (the “intervention”) began. An interrupted time series analysis was conducted and segmented regression analysis was used to assess the immediate and gradual effects of the intervention on hospitalization rates in an intervention group composed of rural residents and a comparison group composed of urban residents primarily. FINDINGS: Before the intervention, the hospitalization rate in the rural population was significantly lower than in the comparison group. Although there was no significant increase or decline in hospitalization rates in the intervention or comparison group before the intervention, after the intervention a significant increase in the hospitalization rate – of 4.6 hospitalizations per 100 000 insured persons per month on average – was noted in the intervention group (P < 0.001). The monthly increase in the hospitalization rate continued for over a year and stabilized thereafter. No increase in the hospitalization rate was observed in the comparison group. CONCLUSION: The primary health-care programme instituted as part of the health system reform process has increased access to hospital care in a population that formerly underutilized hospital services. It has not reduced hospitalizations or hospitalization-related expenditure