Computational Design of Nucleic Acid Feedback Control Circuits

The design of synthetic circuits for controlling molecular-scale processes is an important goal of synthetic biology, with potential applications in future in vitro and in vivo biotechnology. In this paper, we present a computational approach for designing feedback control circuits constructed from nucleic acids. Our approach relies on an existing methodology for expressing signal processing and control circuits as biomolecular reactions. We first extend the methodology so that circuits can be expressed using just two classes of reactions: catalysis and annihilation. We then propose implementations of these reactions in three distinct classes of nucleic acid circuits, which rely on DNA strand displacement, DNA enzyme and RNA enzyme mechanisms, respectively. We use these implementations to design a Proportional Integral controller, capable of regulating the output of a system according to a given reference signal, and discuss the trade-offs between the different approaches. As a proof of principle, we implement our methodology as an extension to a DNA strand displacement software tool, thus allowing a broad range of nucleic acid circuits to be designed and analyzed within a common modeling framework

What God Has Joined Together: The One Threefold Purpose of Marriage

Modern married couples and marriage-minded individuals are often left awash in a sea of confusion aimlessly groping about for a purpose for their marriage, with disastrous societal results. Whereas long-standing Christian tradition has taught a unified threefold marital purpose of three equal elements—procreation, mutual help, and remedy for sin—Enlightenment thinkers and their ideological descendants have introduced a hierarchical marriage teleology with a self-chosen purpose (usually companionship) at the top in order to correct for an alleged countervailing overemphasis on procreation in premodern marital teleology. This thesis will challenge the claim of a relative deficiency in the companionate aspect of premodern marriage teleology by demonstrating a robust theology of unified threefold purpose in key theological writings on marriage, primarily from Augustine, John Chrysostom, Martin Luther, and the marriage rite in the Anglican Book of Common Prayer. Then, an exegesis of 1 Tim. 2:15, one flesh union passages, and other Scriptures pertaining to the purpose of marriage will bolster the joined-together nature of the threefold purpose of marriage elucidated in the historical investigation. Finally, consideration will be given to the significant vocational, ethical, and liturgical implications of the unified threefold purpose of marriage

Long-term psychosocial impact reported by childhood critical illness survivors: a systematic review

Aim: To undertake a qualitative systematic review that explores psychological and social impact, reported directly from children and adolescents at least 6 months after their critical illness. Background: Significant advances in critical care have reduced mortality from childhood critical illness, with the majority of patients being discharged alive. However, it is widely reported that surviving critical illness can be traumatic for both children and their family. Despite a growing body of literature in this field, the psychological and social impact of life threatening critical illness on child and adolescent survivors, more than 6 months post event, remains under-reported. Data sources: Searches of six online databases were conducted up to February 2012. Review methods: Predetermined criteria were used to select studies. Methodological quality was assessed using a standardized checklist. An adapted version of the thematic synthesis approach was applied to extract, code and synthesize data. Findings: Three studies met the inclusion criteria, which were all of moderate methodological quality. Initial coding and synthesis of data resulted in five descriptive themes: confusion and uncertainty, other people’s narratives, focus on former self and normality, social isolation and loss of identity, and transition and transformation. Further synthesis culminated in three analytical themes that conceptualize the childhood survivors’ psychological and social journey following critical illness. Conclusions: Critical illness in childhood can expose survivors to a complex trajectory of recovery, with enduring psychosocial adversity manifesting in the long term. Nurses and other health professionals must be aware and support the potential multifaceted psychosocial needs that may arise. Parents and families are identified as fundamental in shaping psychological and social well-being of survivors. Therefore intensive care nurses must take opportunities to raise parents’ awareness of the journey of survival and provide appropriate support. Further empirical research is warranted to explore the deficits identified with the existing literature

Perceptions of parents on satisfaction with care in the pediatric intensive care unit: the EMPATHIC study

Abstract: PURPOSE: To identify parental perceptions on pediatric intensive care-related satisfaction items within the framework of developing a Dutch pediatric intensive care unit (PICU) satisfaction instrument. METHODS: Prospective cohort study in tertiary PICUs at seven university medical centers in The Netherlands. PARTICIPANTS: Parents of 1,042 children discharged from a PICU. RESULTS: A 78-item questionnaire was sent to 1,042 parents and completed by 559 (54%). Seventeen satisfaction items were rated with mean scores or =1.65, and thus considered of limited value. The empirical structure of the items was in agreement with the theoretically formulated domains: Information, Care a

Identifying patient‐ and family‐centered outcomes relevant to inpatient versus at‐home management of neutropenia in children with acute myeloid leukemia

Efficacy of therapeutic strategies relative to patient‐ and family‐centered outcomes in pediatric oncology must be assessed. We sought to identify outcomes important to children with acute myeloid leukemia and their families related to inpatient versus at‐home management of neutropenia. We conducted qualitative interviews with 32 children ≥8 years old and 54 parents. Analysis revealed the impact of neutropenia management strategy on siblings, parent anxiety, and child sleep quality as being outcomes of concern across respondents. These themes were used to inform the design of a questionnaire that is currently being used in a prospective, multiinstitutional comparative effectiveness trial.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142562/1/pbc26927.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142562/2/pbc26927_am.pd

Crystal structures of 2,6-dibromo-4-methylbenzonitrile and 2,6-dibromo-4-methylphenyl isocyanide

In the title crystals, C8H5Br2N, which are isomorphous, the steric bulk of the methyl group causes neighboring molecules to become mutually inclined. This prevents the formation of planar or nearly planar sheets, which were observed in the trichloro and tribromo analogs. Instead of CN/NC...Br contacts, tetrameric Br...Br contacts are observed. These contacts form tetragonally puckered sheets parallel to (001). The CN/NC and methyl groups are grouped at the peaks and troughs. Both molecules lie across crystallographic mirror planes; thus, the methyl H atoms are disordered over two sets of sites with equal occupancy. The title nitrile is a redetermination. The refinement converged atR[F2&gt; 2σ(F2)] = 0.020, whereas the original determination [Gleason &amp; Britton, (1976).Cryst. Struct. Commun.5, 229–232] hadR= 0.112.</jats:p

Controlled and Efficient Hybridization Achieved with DNA Probes Immobilized Solely through Preferential DNA-Substrate Interactions

Quantitatively correlating the response of DNA sensors to clinically and biologically significant sample abundances requires optimizing the reproducibility of hybridization between DNA targets and surface-bound DNA probes. 1,2 Although gold surfaces are not used in commercial fluorescence-based DNA arrays, gold offers many useful properties as a model substrate 3 and has been successfully used in systematic studies of the interactions governing DNA hybridization near interfaces. 4-8 The hybridization behavior of surface-immobilized DNA probes strongly depends on the probe conformation and on the lateral spacing between adjacent probes. Hybridization is generally enhanced for DNA probes that extend away from a surface, in part because steric hindrance is lower for such brushlike probes than for DNA directly adsorbed on gold. At surface densities e5 × 10 12 cm -2 , typical probe sequences (15-30 nucleotides) can hybridize with efficiencies &gt;60%, 7-10 but at probe densities &gt;1 × 10 13 cm -2 hybridization efficiency is often reduced because of increased electrostatic repulsion and steric constraints. 11-13 Surfaces with DNA probes in upright conformations can be prepared following a number of strategies, including adsorption via a thiol incorporated at one end (DNA-SH) or coupling DNA probes to bifunctional monolayers. [4][5][6][7][8][14][15][16][17][18] Preparing DNA probes * To whom correspondence should be addressed. E-mail: opdahl

Epidemiology of Traumatic Head Injury in Korean Children

The aim of this study was to elucidate the epidemiology of traumatic head injury (THI) among Korean children. A prospective, in-depth trauma survey was conducted in five teaching hospitals. Data from all of the children who attended the emergency department (ED) were analyzed. From June 2008 to May 2009, 2,856 children with THI visited the 5 EDs. The average age of the subjects was 5.6 (SD ± 4.9) yr old, and 1,585 (55.5%) were 0-4 yr old. The male-to-female ratio was 2.3 to 1 (1,979 vs 877). Consciousness levels of the subjects were classified according to the Glasgow Coma Scale (GCS), and 99.1%, 0.6%, and 0.4% were determined as mild, moderate, or severe injury, respectively, according to the GCS categorization. Most injuries occurred at home (51.3%), and the most common mechanism of injury was collision (43.2%). With regard to outcome, 2,682 (93.9%) patients were sent home, and 35 (1.2%) were transferred to another hospital. A total of 133 (4.7%) patients were hospitalized, and 38 (1.3%) underwent surgery. The incidence and characteristics of pediatric THI in Korea are affected by sex, location and injury mechanism

A qualitative study exploring the experiences of parents of children admitted to seven Dutch pediatric intensive care units

Purpose: To explore parents' experiences during the admission of their children to a pediatric intensive care unit (PICU). Method: Qualitative method using in-depth interviews. Thematic analysis was applied to capture parents' experiences. Thirty-nine mothers and 25 fathers of 41 children admitted to seven of the eight PICUs in university medical centers in The Netherlands were interviewed. Results: Parents were interviewed within 1 month after their child's discharge from a PICU. Thematic analysis identified 1,514 quotations that were coded into 63 subthemes. The subthemes were categorized into six major themes: attitude of the professionals; coordination of care; emotional intensity; information management; environmental factors; parent participation. Most themes had an overarching relationship representing the array of experiences encountered by parents when their child was staying in a PICU. The theme of emotional intensity was in particular associated with all the other themes. Conclusions: The findings provided a range of themes and subthemes describing the complexity of the parental experiences of a PICU admission. The subthemes presen

Guidelines for Family-Centered Care in the Neonatal, Pediatric, and Adult ICU.

OBJECTIVE: To provide clinicians with evidence-based strategies to optimize the support of the family of critically ill patients in the ICU. METHODS: We used the Council of Medical Specialty Societies principles for the development of clinical guidelines as the framework for guideline development. We assembled an international multidisciplinary team of 29 members with expertise in guideline development, evidence analysis, and family-centered care to revise the 2007 Clinical Practice Guidelines for support of the family in the patient-centered ICU. We conducted a scoping review of qualitative research that explored family-centered care in the ICU. Thematic analyses were conducted to support Population, Intervention, Comparison, Outcome question development. Patients and families validated the importance of interventions and outcomes. We then conducted a systematic review using the Grading of Recommendations, Assessment, Development and Evaluations methodology to make recommendations for practice. Recommendations were subjected to electronic voting with pre-established voting thresholds. No industry funding was associated with the guideline development. RESULTS: The scoping review yielded 683 qualitative studies; 228 were used for thematic analysis and Population, Intervention, Comparison, Outcome question development. The systematic review search yielded 4,158 reports after deduplication and 76 additional studies were added from alerts and hand searches; 238 studies met inclusion criteria. We made 23 recommendations from moderate, low, and very low level of evidence on the topics of: communication with family members, family presence, family support, consultations and ICU team members, and operational and environmental issues. We provide recommendations for future research and work-tools to support translation of the recommendations into practice. CONCLUSIONS: These guidelines identify the evidence base for best practices for family-centered care in the ICU. All recommendations were weak, highlighting the relative nascency of this field of research and the importance of future research to identify the most effective interventions to improve this important aspect of ICU care