Generation of two hiPSCs lines of two patients carrying truncating mutations in the dimerization domain of filamin C.

Here we introduce the human induced pluripotent stem cell lines (hiPSCs), HIMRi004-A and HIMRi005-A from dermal fibroblasts of a 48-year-old female (HIMRi004-A) carrying missense mutation that translate to the first described filamin C isoform p.W2710X and from a 56-year-old female (HIMRi005-A) carrying a recently described mutation in the same domain p.Y2704X. Both lines are generated via lentiviral expression of OCT4, SOX2, KLF4 and c-MYC. The lines display a typical embryonic stem cell-like morphology, express pluripotency markers, retain a normal karyotype (46, XX) and have the differentiation capacity in all three germ layers. The two lines can be used to elucidate the pathomechanisms of FLNC myofibrillar myopathies and to develop novel therapeutic options.

Active shooter mitigation techniques.

This paper looks at current active shooter mitigation techniques employed by schools throughout the country in an attempt to mitigate casualties during an active shooter event. The researchers modified an existing Columbine High School agent-based model created by Jae Lee, MS, to examine if the introduction of a school resource officer (SRO), concealed carry weapon (CCW) holder, or both would change the outcome of the previous research. RUN.HIDE.FIGHT® scenarios were modeled with the same parameters of the previous work, but now included armed first responders during the incident to assess whether their presence decreased casualties through a reduction in response time. The researchers determined that the addition of either an SRO, CCW holder, or both significantly reduced casualty rates during an active shooter scenario.

Software library for agent-based modeling and simulation of active shooter events.

Software libraries have been used for decades to produce code in a quick and cost-effective manner. The use of well-designed libraries permits software developers and other professionals to create applications due in part to code reusability. Also, good libraries grant lesser skilled developers the opportunity to make high-quality applications they otherwise could not produce. In the field of active shooting incident (ASI) research, various tools have been used for years that give researchers the ability to conduct exploratory research. However, as good as these tools might be, there has been little thought about reusability of these models and associated code. This has hindered the proper advancement of the research field given that researchers must often start from nothing when building a new model. Constant repetition of the same basic tasks has not enabled researchers to expand model fidelity and has limited time to dedicate toward the problem set. This paper proposes the creation of a new agent-based ASI library, made for the AnyLogic® system. The library assists researchers in quickly creating models using a well-defined application programming interface. It also abstracts away implementation details so that the library user does not get waylaid in development. The authors also recreated parts of a large and powerful AnyLogic model to observe the resultant library employment. It was determined that a significant amount of time can be saved building new models, even with the initial version of the library implementation.

Magazine capacity limits and home security.

In response to several mass-casualty shootings in the United States, multiple legislative bodies have promoted or adopted laws that restrict the magazine capacity of firearms. The stated intent of these laws is to reduce the number of rounds a bad actor can fire in a mass-casualty situation. However, objectors argue that the laws not only are ineffective but could also cause an undue burden on the ability of law-abiding gun owners to protect themselves. Using agent-based simulation modeling, a home-invasion model including two-armed bad actors and a one-armed homeowner was created to test this hypothesis. The homeowner engaged the bad actors with different capacity magazines, and the survival rate was recorded and compared across the spectrum of capacities. This model showed that reducing the homeowner's magazine capacity resulted in an increased casualty rate for the homeowner.

Active shooter mitigation strategies in small rural churches.

Gun violence in places of worship (POW) has long been an issue and has been addressed repeatedly in the literature. Contextually, most of the research has been pertinent to relatively large POW, situated in an urban setting. However, rural churches have not been addressed, and they appear to have a far less defensive posture, mainly because of their remote location and the extended time required for first responders to arrive, which in turn requires a higher level of independent operation in terms of defense and medical response. Having retained an off-duty officer is a strong deterrent and provides the ability to handle any issues that may arise, including lower violence level events. If retaining an officer is not an option, having a well-trained volunteer armed team and a clear plan of action is vital to surviving such an event. Furthermore, due to the extended response and transport time, it is critical to have proper medical training, such as Stop the Bleed® and cardio-pulmonary resuscitation. This article's focus is not only on response but preparedness, which reinforces the response, as well as prevention and deterrence. An exhaustive best practices review has informed the solutions offered, supplemented by experience and recommendations of a highly experienced physical security expert and a police officer member of a Special Weapons and Tactics (SWAT) team.

Disaster response using the circular economy: A timeline review of the literature.

Construction materials are, by the very nature of building something, an investment in the future. Every project highlights the possibilities of the building or structure, but when a catastrophic event renders it useless, the landfills grow, and the resources' potential is lost. The end of a building does not need to mean the end of those materials in it. As part of the growing momentum behind sustainability metrics sought out by investment and construction firms alike, the potential for returns on investment already exists. The United States has the National Response Framework and international commitments like the Sendai Framework for Disaster Risk Reduction that signify the appetite to embrace the latest innovations in response techniques and technologies. This literature review will focus on how the construction and demolition industry can lead as the primary ameliorators and enablers of remedying this shortfall in innovative adoption uptake by engaging and applying the growing practice of the circular economy to their own debris management regimens.

[Periprosthetic infection after total hip replacement : Risk factors for an early infection after primary implantation]. / Periprothetischer Infekt nach Hüftprothesenimplantation : Risikofaktoren für die Entwicklung einer Frühinfektion nach Primärimplantation.

BACKGROUND: Periprosthetic infection is one of the most serious complications in primary arthroplasty. The infection rates reported in the current literature range from 0.36 to 2.23%. OBJECTIVES: The aim of this retrospective case-control study was to determine preoperative risk factors for the occurrence of early periprosthetic infection after primary hip arthroplasty. MATERIALS AND METHODS: The influence of patient age, gender, body mass index (BMI), C­reactive protein, preoperative leukocyte count and morbidity level (American Society of Anaesthesiologists score) on the occurrence of periprosthetic early infection of the hip joint was examined, and their correlation was investigated. RESULTS: Of the 1383 patients followed up, 25 were diagnosed with early infection. With an increase in BMI of 1 kg/m2, the risk of periprosthetic early infection increased by 12.1% (p < 0.001). In addition, using the receiver operating characteristic (ROC) curve, a BMI ≥ 29 kg/m2 is identified as a significant cut-off for the increased likelihood of periprosthetic hip infection. Using the ROC curve, a preoperative CrP value > 5 mg/l can be validated as a cut-off value for an increased risk of early infection. Using binary logistic regression, no influence of CrP > 5 mg/l on the development of early infection was statistically proven (p = 0.065). CONCLUSIONS: Patients with a BMI ≥ 29 kg/m2 should be informed about the increased risk of periprosthetic early infection after hip prosthesis implantation and a risk assessment should be performed. Furthermore, the determination of the preoperative CrP value should be considered standard.

Agent-based modeling for theme park evacuation.

Each year theme parks can see up to 20 million patrons, but often little effort is put into planning for an emergency evacuation. In this study, we built a multiagent simulation model using AnyLogic® 8.5.1. The model was based on a preliminary design of a theme park provided by AOA Builds, Orlando. This research had two goals: the first was to compare evacuation time when the park is full (1) using only the main guest gate and (2) using all seven available exits. The second goal was to model first responder response time between various start and end locations within the park. Using only the main gate, evacuation took an average of 14 minutes and 51 seconds. Using all seven gates results in an average evacuation time of 11 minutes and 58 seconds. This was due to a gate being overwhelmed causing a delay in overall evacuation time. If that gate is not included in the calculation, the average evacuation time drops to 6 minutes and 44 seconds. For the purpose of measuring response times, four starting locations were chosen with the guidance of a subject matter expert. These locations included response teams positioned at the front gate, at a police station, at the service area behind a main attraction, and mobile patrol walking around the park. Based on our testing, walking around the park was the best option in terms of response time, using the main gate was 53.7 percent faster than other options and, using all seven gates, was 60.7 percent faster during an evacuation using all seven exits.

POD variant comparisons.

Points of distribution, also known as points of dispensing (POD), are a means for public and private organizations to assist their communities in times of crisis. There are two principal categories of PODs, open and closed, but all PODs differ in design, properties, and application. This study investigates two POD variations: drive-through and supervisor, which have their own unique requirements for being stood up, run, and shut down, as well as differing requirements for planning, staffing, and logistics. There are also similarities in the requirements that each POD category share which lead to certain efficiencies in planning for POD standup, execution, and shutdown. The primary findings of this paper are that planners cannot rely on one POD design and its properties to accommodate every situation, and each POD design has its own strengths and weaknesses. These are related to staffing, security, space requirements, and material logistics needs. Flexibility should be exercised when choosing the correct design, and implementing the proper strategy is key to standing up and executing a POD that will best serve a community. Every situation is different and factors such as population, available infrastructure, resource requirements, and individual skill of the POD staff all influence the design of a POD. Planners should consider resources such as available volunteers, trained personnel (medical and security), and buildings or outdoor space available to run a POD. With proper planning, a POD is an excellent tool to effectively and efficiently serve the public.

A case for standardized communications for point of distribution operations.

OBJECTIVE: Propose standardized communication formats and procedures at the point of distribution (POD) sites to facilitate the effective management and alleviate friction points that may occur while responding to a widespread medical incident within the National Incident Management System (NIMS). DESIGN: Through observation of POD operations and interviews with key personnel in Indiana and county emergency management agencies (EMA), identify current communication practices and propose a structured command and control (C2) framework that would streamline management requirements during a widespread activation. SETTING: The State of Indiana, various counties throughout Indiana. CONCLUSIONS: Current C2 practices are adequate for small-scale events. However, a standardized approach to the C2 and reporting framework may provide more responsive situational awareness and incident management of larger-scale medical incidents within Indiana.

Cystinuria in the maned wolf of South America.

Of 42 maned wolves in zoos or live-trapped in Brazil, 34 had excessive cystine in their urine. Renal clearance studies of five of the affected wolves revealed a variable defect for the reabsorption of cystine and dibasic amino acids. The renal tubular handling of other solutes including glucose, phosphate, sodium, potassium, and uric acid was considered normal. Urinary calculi composed of cystine were found in four wolves and proved fatal in three of them. With the exception of the high incidence in this species, this hereditary disease resembles the disorder described in dogs and humans.

Impact of HBV genotype and mutations on HBV DNA and qHBsAg levels in patients with HBeAg-negative chronic HBV infection.

BACKGROUND: HBV DNA and quantitative (q)HBsAg levels as prognostic markers for HBV-related disease are mostly validated in Asia and their significance in Western populations is uncertain. AIM: To analyse the impact of the HBV genotype and frequent mutations in precore (PC), basal core promoter (BCP) and preS on HBV DNA and qHBsAg levels. METHODS: HBV DNA and qHBsAg serum levels of 465 patients with HBeAg-negative chronic HBV infection were correlated with the HBV genotype and mutations in PC, BCP and preS. For a detailed analysis of the molecular virology, genotype A2 genomes harbouring these mutations were analysed for replication efficacy and HBsAg release in cell culture. RESULTS: While no impact of the HBV genotype on HBV DNA levels was observed, qHBsAg levels differed up to 1.4 log among the genotypes (P < 0.001), reflected by large differences regarding the 1000 IU/mL HBsAg cut-off. While PC mutations were associated with higher (P < 0.001), BCP mutations were associated with lower HBV DNA levels (P < 0.001). Higher qHBsAg levels were associated with preS and lower levels with PC mutations (P < 0.001 and P = 0.001, respectively). The cell culture experiments revealed a higher HBsAg release and shorter filaments in case of a HBV genome harbouring a preS deletion. In contrast, a perinuclear HBsAg accumulation was detected for the PC and BCP-variants, reflecting an impaired HBsAg release. CONCLUSIONS: qHBsAg serum levels depend on the HBV genotype and together with HBV DNA levels on frequent mutations in PC, BCP and preS in HBeAg-negative patients. qHBsAg cut-offs when used as prognostic markers require genotype-dependent validation.

Comparison of ticarcillin and piperacillin in Kenney's semen extender.

Ticarcillin and piperacillin were compared to determine their effect on sperm motility and bacterial growth of equine semen samples diluted in Kenney's glucose skim milk semen extender. Each ejaculate (n=11) was divided into three portions and glucose skim milk semen extender solution was added. The control semen extender solution contained extended semen and no antibiotic, whereas ticarcillin and piperacillin solutions contained extended semen plus 1.0mg/mL of ticarcillin or piperacillin, respectively. An aliquot was removed (1h after collection) to evaluate sperm motility and microbial concentration. All three solutions were stored at 4 degrees C and aliquots were obtained at 24 and 48 h to determine sperm motility and microbial concentration. Mean percentages of motile and progressively motile sperm did not differ significantly among control and antibiotic-containing solutions after storage. Control-extended semen samples from ejaculates of stallions (n=11) were contaminated with aerobic gram-positive and gram-negative bacteria. In solutions that contained either antibiotic, growth of these microbes was inhibited after 1, 24, and 48 h at 4 degrees C. Semen samples from stallions (n=5) were extended with Kenney's glucose skim milk extender containing no antibiotic, ticarcillin or piperacillin and then inoculated with approximately 5 x 10(2)CFU/mL Klebsiella pneumoniae or Pseudomonas aeruginosa; there was no significant difference between antibiotics in the inhibition of microbial growth. In conclusion, piperacillin was an appropriate alternative to ticarcillin in extenders for equine semen.

Selective growth of transformed cell lines by rat liver perfusate.

Perfused rat liver releases growth-promoting activity for viral, spontaneous, and chemically transformed cells. After 5 days of incubation with perfusate, cell lines 3T12-NY (a spontaneous fibroblast transformant), NQ-T1 (a chemically transformed fibroblast line), W-8 (a chemically transformed epithelial rat liver cell line increase in cell growth above controls. Their respective normal counterparts: 3T3 Cl 42, A31-714, K-16, and HEF are not so stimulated. Within another set, the virally transformed mouse fibroblast cell line, SV3T3, exhibits a 27-fold increase in growth; however, 3T3 (mouse, fibroblasts), Py3T3 (polyomatransformed 3T3 cells), SV-Fl2-101 (a flat revertant line), and SV-Py-3T3 (a doubly transformed line) are nonresponsive. Perfused rat liver also release survival activity for SV-3T3 cells. The growth-stimulating activity in liver perfusate is selective for transformed cells. It is suggested that the liver may play a role in suporting neoplasia in vivo.

Cutaneous and Subcutaneous Soft Tissue Tumours in Snakes: A Retrospective Study of 33 Cases.

Cutaneous and subcutaneous soft tissue tumours have been rarely described in detail in snakes. Several malignant entities show strikingly similar histological patterns and therefore the term soft tissue sarcoma (STS) has become a standard histopathological diagnosis. The present study characterizes soft tissue tumours in 33 snakes. Samples included 29 surgically excised masses and four carcasses. Additionally, six animals were humanely destroyed and submitted for necropsy examination following tumour recurrence. Benign neoplasms (n = 8) were described as lipomas of varying differentiation. Recurrence was observed in two of five snakes in which the clinical course was recorded. Malignant neoplasms (n = 25) were diagnosed as STS and graded according to a three-point system previously applied to canine STS. Five (20%) of the primary tumours were classified as grade 1, eleven (44%) as grade 2 and nine (36%) as grade 3 sarcomas. Clinically, recurrence of STS was observed in 11 of 17 cases with available follow-up information. Pathologically, multiple cutaneous metastases were found in one grass snake (Natrix natrix), while visceral metastases were observed in one carpet python (Morelia spilota) and two corn snakes (Pantherophis guttatus). Metastatic risk appears to increase with histological grade. Surgical excision generally represents the current therapy of choice for STS. This study includes the first reports of conventional lipomas in a ribbon snake (Thamnophis radix), angiolipomas in a black-headed python (Aspidites melanocephalus) and a corn snake as well as of STS in a Jamaican boa (Epicrates subflavus), emerald tree boa (Corallus caninus), grass snake (N. natrix), African house snake (Lamprophis fuliginosus), California kingsnake (Lampropeltis getula californiae) and common garter snake (Thamnophis sirtalis).

Integration of proviral DNA into the PDGF beta-receptor gene in HTLV-I-infected T-cells results in a novel tyrosine kinase product with transforming activity.

We have previously shown that noninfected human T-cell lines express the canonical 5.7 kb mRNA coding for the type beta platelet-derived growth factor-receptor (PDGF beta-receptor), whereas HTLV-I-infected T-cell lines express a novel PDGF beta-receptor mRNA of 3.8 kb. In this report, we have extended those studies to molecularly characterize the 3.8 kb PDGF beta-receptor mRNA and show that it has resulted from integration of an apparently undeleted HTLV-I provirus into the PDGF beta-receptor gene in an orientation enabling expression of a truncated PDGF beta-receptor mRNA using the 3' HTLV-I long terminal repeat as a promoter. Further, NIH3T3 cells transfected with a plasmid containing the truncated PDGF beta-receptor ORF plasmid generate colonies in soft agar with more cells per colony than untransfected cells, or cells transfected with the Tax 1 or PDGF-B (c-sis) plasmids. These results indicate that the truncated PDGF beta-receptor protein acquires transforming capability and that HTLV-I-induced truncation of PDGF beta-receptor may correlate with HTLV-I-associated neoplasia of human T-cells.

Transposable element insertions respecify alternative exon splicing in three Drosophila myosin heavy chain mutants.

Insertions of transposable elements into the myosin heavy chain (Mhc) locus disrupt the regulation of alternative pre-mRNA splicing for multi-alternative exons in the Mhc2, Mhc3, and Mhc4 mutants in Drosophila. Sequence and expression analyses show that each inserted element introduces a strong polyadenylation signal that defines novel terminal exons, which are then differentially recognized by the alternative splicing apparatus. Mhc2 and Mhc4 have insertion elements located within intron 7c and exon 9a, respectively, and each expresses a single truncated transcript that contains an aberrant terminal exon defined by the poly(A) signal of the inserted element and the 3' acceptor of the upstream common exon. In Mhc3, a poly(A) signal inserted into Mhc intron 7d defines terminal exons using either the upstream 3' acceptor of common exon 6 or the 7d acceptor, leading to the expression of 4.1- and 1.7-kb transcripts, respectively. Acceptor selection is regulated in Mhc3 transcripts, where the 3' acceptor of common Mhc exon 6 is preferentially selected in larvae, whereas the alternative exon 7d acceptor is favored in adults. These results reflect the adult-specific use of exon 7d and suggest that the normal exon 7 alternative splicing mechanism continues to influence the selection of exon 7d in Mhc3 transcripts. Overall, transposable element-induced disruptions in alternative processing demonstrate a role for the nonconsensus 3' acceptors in Mhc exons 7 and 9 alternative splicing regulation.

Impact of RO-desalted water on distribution water qualities.

A large-scale pilot distribution study was conducted to investigate the impacts of blending different source waters on distribution water qualities, with an emphasis on metal release (i.e. corrosion). The principal source waters investigated were conventionally treated ground water (G1), surface water processed by enhanced treatment (S1), and desalted seawater by reverse osmosis membranes (RO). Due to the nature of raw water quality and associated treatment processes, G1 water had high alkalinity, while S1 and RO sources were characterized as high sulfate and high chloride waters, respectively. The blending ratio of different treated waters determined the quality of finished waters. Iron release from aged cast iron pipes increased significantly when exposed to RO and S1 waters: that is, the greater iron release was experienced with alkalinity reduced below the background of G1 water. Copper release to drinking water, however, increased with increasing alkalinity and decreasing pH. Lead release, on the other hand, increased with increasing chloride and decreasing sulfate. The effect of pH and alkalinity on lead release was not clearly observed from pilot blending study. The flat and compact corrosion scales observed for lead surface exposed to S1 water may be attributable to lead concentration less than that of RO water blends.

Mitigating active shooter impact: Analysis for policy options based on agent/computer-based modeling.

UNLABELLED: Active shooting violence at confined settings, such as educational institutions, poses serious security concerns to public safety. In studying the effects of active shooter scenarios, the common denominator associated with all events, regardless of reason/intent for shooter motives, or type of weapons used, was the location chosen and time expended between the beginning of the event and its culmination. This in turn directly correlates to number of casualties incurred in any given event. The longer the event protracts, the more casualties are incurred until law enforcement or another barrier can react and culminate the situation. OBJECTIVE: Using AnyLogic technology, devise modeling scenarios to test multiple hypotheses against free-agent modeling simulation to determine the best method to reduce casualties associated with active shooter scenarios. DESIGN, SETTING, SUBJECTS: Test four possible scenarios of responding to active shooter in a public school setting using agent-based computer modeling techniques-scenario 1: basic scenario where no access control or any type of security is used within the school; scenario 2, scenario assumes that concealed carry individual(s) (5-10 percent of the work force) are present in the school; scenario 3, scenario assumes that the school has assigned resource officer; scenario 4, scenario assumes that the school has assigned resource officer and concealed carry individual(s) (5-10 percent) present in the school. MAIN OUTCOMES MEASURED: Statistical data from modeling scenarios indicating which tested hypothesis resulted in fewer casualties and quicker culmination of event. RESULTS: The use of AnyLogic proved the initial hypothesis that a decrease on response time to an active shooter scenario directly reduced victim casualties. CONCLUSIONS: Modeling tests show statistically significant fewer casualties in scenarios where on scene armed responders such as resource officers and concealed carry personnel were present.