Experimental verification of principal losses in a regulatory particulate matter emissions sampling system for aircraft turbine engines.

A sampling system for measuring emissions of nonvolatile particulate matter (nvPM) from aircraft gas turbine engines has been developed to replace the use of smoke number and is used for international regulatory purposes. This sampling system can be up to 35 m in length. The sampling system length in addition to the volatile particle remover (VPR) and other sampling system components lead to substantial particle losses, which are a function of the particle size distribution, ranging from 50 to 90% for particle number concentrations and 10-50% for particle mass concentrations. The particle size distribution is dependent on engine technology, operating point, and fuel composition. Any nvPM emissions measurement bias caused by the sampling system will lead to unrepresentative emissions measurements which limit the method as a universal metric. Hence, a method to estimate size dependent sampling system losses using the system parameters and the measured mass and number concentrations was also developed (SAE 2017; SAE 2019). An assessment of the particle losses in two principal components used in ARP6481 (SAE 2019) was conducted during the VAriable Response In Aircraft nvPM Testing (VARIAnT) 2 campaign. Measurements were made on the 25-meter sample line portion of the system using multiple, well characterized particle sizing instruments to obtain the penetration efficiencies. An agreement of ± 15% was obtained between the measured and the ARP6481 method penetrations for the 25-meter sample line portion of the system. Measurements of VPR penetration efficiency were also made to verify its performance for aviation nvPM number. The research also demonstrated the difficulty of making system loss measurements and substantiates the E-31 decision to predict rather than measure system losses.

Interventions to treat posttraumatic stress disorder in partnership with primary care: A review of feasibility and large randomized controlled studies.

OBJECTIVE: Evidence-based therapies for posttraumatic stress disorder are underutilized and at times unavailable in specialty settings. We reviewed the literature on interventions to treat PTSD within primary care to make recommendations on their effectiveness as treatment modalities or ways to improve engagement in specialty care. METHOD: We searched PubMed, PsychInfo, CINHAL, and Cochrane Reviews databases using search terms related to PTSD and primary care. We excluded clinical guidelines and studies of screening only or subthreshold PTSD. RESULTS: 524 articles were identified. Twenty-one papers on 15 interventions met review criteria. Seven interventions focus on individual therapies studied via small feasibility studies to prepare for full-scale intervention research. Eight describe treatment programs in primary care based on collaborative care that included medication management, tracking outcomes, referral services, and for some psychotherapy (versus psychotherapy referral). Ten interventions were feasibility studies which precludes meaningful comparison of effect sizes. Of the four RCTs of treatment programs, only two including some psychotherapy found improvements in PTSD symptoms. CONCLUSION: More research is needed to adapt treatment for PTSD to primary care. Collaborative care may be a promising framework for improving the reach of PTSD treatments when psychotherapy is offered within the collaborative care team.

The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome.

Missense MECP2 variants can have various phenotypic effects ranging from a normal phenotype to typical Rett syndrome (RTT). In females, the phenotype can also be influenced by the X-inactivation pattern. In this study, we present detailed clinical descriptions of six patients with a rare base-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism. Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X-inactivation patterns in target tissues.

Mycobacterium llatzerense lung infection in a liver transplant recipient: case report and review of the literature.

Nontuberculous mycobacteria are increasingly encountered pathogens in organ transplant recipients. We report the first case of human disease attributed to Mycobacterium llatzerense that occurred in a liver transplant recipient in the midwestern United States who developed pneumonia and describe the treatment of this patient.

Insurer and employer views on pediatric obesity treatment: a qualitative study.

OBJECTIVE: The effectiveness of group-based comprehensive, multidisciplinary (stage 3) pediatric weight management programs is backed by a growing body of literature, yet insurance coverage of these programs is scarce to nonexistent, limiting their reach and long-term survival. The objective of this study was to better understand the perspectives of insurers and large employers on the issue of group-based treatment coverage. DESIGN AND METHODS: The authors performed a qualitative study utilizing structured interviews with these stakeholders, following accepted techniques. RESULTS: Six major themes emerged: cost, program effectiveness, corporate social responsibility, secondary parental (employee) benefits, coverage options and new benefit determination. CONCLUSION: Future efforts to secure payment for group-based pediatric weight management programs should address these key themes.

Few Associations Found between Mold and Other Allergen Concentrations in the Home versus Skin Sensitivity from Children with Asthma after Hurricane Katrina in the Head-Off Environmental Asthma in Louisiana Study.

Mold and other allergen exposures exacerbate asthma symptoms in sensitized individuals. We evaluated allergen concentrations, skin test sensitivities, and asthma morbidity for 182 children, aged 4-12 years, with moderate to severe asthma, enrolled 18 months after Katrina, from the city of New Orleans and the surrounding parishes that were impacted by the storm, into the Head-off Environmental Asthma in Louisiana (HEAL) observational study. Dust (indoor) and air (indoor and outdoor) samples were collected at baseline of 6 and 12 months. Dust samples were evaluated for dust mite, cockroach, mouse, and Alternaria by immunoassay. Air samples were evaluated for airborne mold spore concentrations. Overall, 89% of the children tested positive to ≥1 indoor allergen, with allergen-specific sensitivities ranging from 18% to 67%. Allergen concentration was associated with skin sensitivity for 1 of 10 environmental triggers analyzed (cat). Asthma symptom days did not differ with skin test sensitivity, and surprisingly, increased symptoms were observed in children whose baseline indoor airborne mold concentrations were below median levels. This association was not observed in follow-up assessments. The lack of relationship among allergen levels (including mold), sensitivities, and asthma symptoms points to the complexity of attempting to assess these associations during rapidly changing social and environmental conditions.

Comparison of five commercial DNA extraction kits for the recovery of Yersinia pestis DNA from bacterial suspensions and spiked environmental samples.

AIM: To evaluate commercial DNA extraction kits for their ability to isolate DNA from Yersinia pestis suspensions and spiked environmental samples. METHODS AND RESULTS: Five commercially available DNA extraction kits were evaluated: the ChargeSwitch gDNA Mini Bacteria Kit, the IT 1-2-3 Sample DNA Purification Kit, the MasterPure Complete DNA and RNA Purification Kit, the QIAamp DNA Blood Mini Kit and the UltraClean Microbial DNA Isolation Kit. The extraction methods were performed upon six Y. pestis strains and spiked environmental specimens, including three swab types and one powder type. Taqman real-time PCR analysis revealed that the use of the MasterPure kit resulted in DNA with the most consistently positive results and the lowest limit of detection from Y. pestis suspensions and spiked environmental samples. CONCLUSION: Comparative evaluations of the five commercial DNA extraction methods indicated that the MasterPure kit was superior for the isolation of PCR-amplifiable DNA from Y. pestis suspensions and spiked environmental samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study can assist diagnostic laboratories with selecting the best extraction method for processing environmental specimens for subsequent detection of Y. pestis by real-time PCR.

Herbicide sorption coefficients in relation to soil properties and terrain attributes on a cultivated prairie.

The sorption of 2,4-D and glyphosate herbicides in soil was quantified for 287 surface soils (0-15 cm) collected in a 10 x 10 m grid across a heavily eroded, undulating, calcareous prairie landscape. Other variables that were determined included soil carbonate content, soil pH, soil organic carbon content (SOC), soil texture, soil loss or gain by tillage and water erosion, and selected terrain attributes and landform segments. The 2,4-D sorption coefficient (Kd) was significantly associated with soil carbonate content (-0.66; P < 0.001), soil pH (-0.63; P < 0.001), and SOC (0.47; P < 0.001). Upper slopes were strongly eroded and thus had a significantly greater soil carbonate content and less SOC compared with lower slopes that were in soil accumulation zones. The 2,4-D Kd was almost twice as small in upper slopes than in lower slopes. The 2,4-D Kd was also significantly associated with nine terrain attributes, particularly with compounded topographic index (0.59; P < 0.001), gradient (-0.48; P < 0.001), mean curvature (-0.43; P < 0.001), and plan curvature (-0.42 P < 0.001). Regression equations were generated to estimate herbicide sorption in soils. The predicted power of these equations increased for 2,4-D when selected terrain attributes were combined with soil properties. In contrast, the variation of glyphosate sorption across the field was much less dependent on our measured soil properties and calculated terrain attributes. We conclude that the integration of terrain attributes or landform segments in pesticide fate modeling is more advantageous for herbicides such as 2,4-D, whose sorption to soil is weak and influenced by subtle changes in soil properties, than for herbicides such as glyphosate that are strongly bound to soil regardless of soil properties.

Communication skills training in postgraduate medicine: the development of a new course.

It has long been accepted that communication is of central importance in healthcare, and a core aspect of clinical competence. Many educational institutions and Royal Colleges now reflect this and consider communication skills a priority in postgraduate examination. The new examination "Practical Assessment of Clinical and Examination Skills" has replaced the Royal College of Physicians MRCP part 2 clinical and oral examination. This examination now consists of five clinical stations, two of which focus on communication skills. A short course for postgraduate trainees has been designed to address the communication skills requirements of the part 2 clinical examination. The aims, development, and content of the course are described. Emphasis is placed on candidates practising skills with patients and receiving feedback during the course. Evidence suggests that practice with feedback is an essential ingredient of communication skills courses, and is more effective than other methods such as observing experts or video examples, or simply discussing issues in communication. Results of a preliminary evaluation indicate that the course was perceived as valuable by candidates and that the aims, format, and content were appropriate. Although the preliminary evaluation was largely positive, it could be argued that the acid test of the effectiveness of a course is an objective evaluation of skills, observed before and after the course, a development that is being considered for future evaluation of the course. Recommendations for applying this type of training to postgraduate trainees in any branch of medicine are given.

Applications of eTag trade mark assay platform to systems biology approaches in molecular oncology and toxicology studies.

We have developed a universal eTag trade mark multiplex assay platform that can be uniquely applied to survey the molecule profiles of biologic systems in sub-global large-scale analyses. The effectiveness of eTag trade mark assays when applied to focused system biology studies in molecular oncology and predictive toxicology is herein described while reviewing the current methods commonly used. The multi-analyte and multi-parameter assay approach for parallel analysis will form the basis of an emerging paradigm of multiplexed molecular profiling for signaling pathway networks and various aspects of drug development processes.

Androgen excess in women: experience with over 1000 consecutive patients.

The objective of the present study was to estimate the prevalence of the different pathological conditions causing clinically evident androgen excess and to document the degree of long-term success of suppressive and/or antiandrogen hormonal therapy in a large consecutive population of patients. All patients presenting for evaluation of symptoms potentially related to androgen excess between October 1987 and June 2002 were evaluated, and the data were maintained prospectively in a computerized database. For the assessment of therapeutic response, a retrospective review of the medical chart was performed, after the exclusion of those patients seeking fertility therapy only, or with inadequate follow-up or poor compliance. A total of 1281 consecutive patients were seen during the study period. Excluded from analysis were 408 patients in whom we were unable to evaluate hormonal status, determine ovulatory status, or find any evidence of androgen excess. In the remaining population of 873 patients, the unbiased prevalence of androgen-secreting neoplasms was 0.2%, 21-hydroxylase-deficient classic adrenal hyperplasia (CAH) was 0.6%, 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH) was 1.6%, hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome was 3.1%, idiopathic hirsutism was 4.7%, and polycystic ovary syndrome (PCOS) was 82.0%. Fifty-nine (6.75%) patients had elevated androgen levels and hirsutism but normal ovulation. A total of 257 patients were included in the assessment of the response to hormonal therapy. The mean duration of follow-up was 33.5 months (range, 6-155). Hirsutism improved in 86%, menstrual dysfunction in 80%, acne in 81%, and hair loss in 33% of patients. The major side effects noted were irregular vaginal bleeding (16.1%), nausea (13.0%), and headaches (12.6%); only 36.6% of patients never complained of side effects. In this large study of consecutive patients presenting with clinically evident androgen excess, specific identifiable disorders (NCAH, CAH, HAIRAN syndrome, and androgen-secreting neoplasms) were observed in approximately 7% of subjects, whereas functional androgen excess, principally PCOS, was observed in the remainder. Hirsutism, menstrual dysfunction, or acne, but not alopecia, improved in the majority of patients treated with a combination suppressive therapy; although more than 60% experienced side effects.

Recombination hotspot in NF1 microdeletion patients.

Neurofibromatosis type 1 (NF1) patients that are heterozygous for an NF1 microdeletion are remarkable for an early age at onset and an excessive burden of dermal neurofibromas. Microdeletions are predominantly maternal in origin and arise by unequal crossover between misaligned NF1REP paralogous sequence blocks which flank the NF1 gene. We mapped and sequenced the breakpoints in several patients and designed primers within each paralog to specifically amplify a 3.4 kb deletion junction fragment. This assay amplified a deletion junction fragment from 25 of the 54 unrelated NF1 microdeletion patients screened. Sequence analysis demonstrated that each of the 25 recombination events occurred in a discrete 2 kb recombination hotspot within each of the flanking NF1REPs. Two recombination events were accompanied by apparent gene conversion. A search for recombination-prone motifs revealed a chi-like sequence; however, it is unknown whether this element stimulates recombination to occur at the hotspot. The deletion-junction assay will facilitate the prospective identification of patients with NF1 microdeletion at this hotspot for genotype-phenotype correlation studies and diagnostic evaluation.

Expression of a truncated keratin 5 may contribute to severe palmar--plantar hyperkeratosis in epidermolysis bullosa simplex patients.

Epidermolysis bullosa simplex are dominant disorders of skin fragility characterized by intraepidermal blistering upon mild mechanical trauma. Skin fragility is caused by expression of either an abnormal keratin 5 or an abnormal keratin 14 protein, which compromises the structure and function of the keratin cytoskeleton of basal cells. We report an epidermolysis bullosa simplex patient with a novel single base substitution (A-->T1414) that changes the lysine residue at amino acid 472 to a non-sense codon (K472X). This change predicts the synthesis of a truncated keratin 5, missing 119 amino acids, including the entire tail domain and the highly conserved KLLEGE motif at the carboxy terminus of the 2B domain of the central rod. Expression of an altered keratin 5, of predicted mass and pI for the product of the K472X allele, was documented by one- and two-dimensional western blots of protein extracts from patient skin. Ultrastructural analysis of the patient's nonhyperkeratotic skin was remarkable for basal keratinocytes with dense and irregular keratin filaments proximal to the basement membrane. Keratinocytes, transfected with a cDNA carrying the A-->T1414 non-sense mutation, overexpressed a truncated keratin 5, and showed a disorganized and collapsed keratin filament cytoskeleton. This is the second epidermolysis bullosa simplex patient reported with a premature termination mutation in the KLLEGE motif. The remarkable occurrence of severe palmar--plantar hyperkeratosis in both patients suggests that the keratin 5 tail domain may have unrecognized, but important, normal functions in palmar-plantar tissues.

Evidence that juvenile myelomonocytic leukemia can arise from a pluripotential stem cell.

Children with neurofibromatosis type 1 (NF1) carry germline mutations in one allele of the NF1 gene and are predisposed to myeloid malignancies, particularly juvenile myelomonocytic leukemia (JMML). Disruption of the remaining NF1 allele can be found in malignant cells. Flow cytometric cell sorting techniques to isolate the malignant cell populations and molecular genetic methods to assay for somatic loss of the normal NF1 allele were used to study an unusual child with NF1 and JMML who subsequently had T-cell lymphoma. The data show that malignant JMML and lymphoma cells share a common loss of genetic material involving the normal NF1 gene and approximately 50 Mb of flanking sequence, suggesting that the abnormal T-lymphoid and myeloid populations were derived from a common precursor cell. These data support the hypothesis that JMML can arise in a pluripotent hematopoietic cell.

Formula for surgical practice resuscitation in an academic medical center.

BACKGROUND: Managing patient referrals for surgical consultation in an academic practice has traditionally emphasized clinical rather than service expertise. However, assuring both efficiency and accuracy in the initial consultation have become critical early measures of quality care. METHODS: In partnership with the academic medical center administration, current practice was analyzed. Performance and communication standards were established around an ideal patient experience. A new ambulatory consultation process was developed; and flowcharting methods for resource allocation, statistical process control, and pre-visit data collection were used to reduce patient administrative time. Automated referral reports engaged referring physicians throughout the consultation. RESULTS: Accurate insurance and referral authorization have been provided for all patients, including the 4% who are underinsured. Patient, provider, and referring physician satisfaction has increased significantly. Staff time investment has progressively declined from 52 +/- 11 (95% confidence) minutes to 34 +/- 10 minutes for most patients. Realignment of tasks has reduced the administrative time spent by the patient by 32% without compromising clinical time. New patient volume increased by 29% per year, maintaining regional market share. CONCLUSIONS: Expertise in the process of consultation delivery is feasible and will be increasingly critical to the survival of academic surgical practice in a competitive market.

Pulmonary function after modified venovenous ultrafiltration in infants: a prospective, randomized trial.

OBJECTIVE: We sought to examine the effects of modified venovenous ultrafiltration after cardiopulmonary bypass on pulmonary compliance in infants. METHODS: We prospectively enrolled 38 infants undergoing their first operation for congenital heart disease. Infants were randomized to receive 20 minutes of modified ultrafiltration after bypass or control. Static and dynamic compliance was measured after induction of anesthesia, before and immediately after filtration in the operating theater, 1 hour after return to the pediatric intensive care unit, and 24 hours after the operation. Length of time on the ventilator, inotropic requirements, and length of stay in the intensive care unit were recorded. RESULTS: Modified ultrafiltration produced a significant immediate improvement in dynamic (pre-ultrafiltration 2.5 +/- 1.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.7 mL/cm H(2)O, P =.03) and static (pre-ultrafiltration 2.1 +/- 0.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.1 mL/cm H(2)O, P =.04) compliance. However, there was no significant difference in the change in dynamic (P =.3) or static (P =.7) compliance in the ultrafiltration and control groups when compared before the operation, after the operation, and at 24 hours. There was no significant difference in the time to extubation between patients and control subjects (140 +/- 91 hours vs 90 +/- 58 hours) or the length of intensive care unit stay (10.0 +/- 9.1 days vs 7.4 +/- 5.7 days). CONCLUSIONS: Modified ultrafiltration produces an improvement in pulmonary compliance after bypass in infants. However, these improvements are not sustained past the immediate post-ultrafiltration period and do not lead to a decreased length of intubation or intensive care unit stay.

Refined mapping of the human serotonin transporter (SLC6A4) gene within 17q11 adjacent to the CPD and NF1 genes.

The SLC6A4 gene encodes the serotonin transporter, the target of an important class of antidepressant drugs (serotonin selective reuptake inhibitors). Polymorphisms in the SLC6A4 gene have been reported to be associated with susceptibility to depression and other psychiatric disorders. We have constructed a 1 Mb YAC and PAC contig which harbours both the SLC6A4 and the carboxypeptidase D (CPD) genes. The order of loci within the contig was cen-D17S975-D17S1549-24R-D17S1294-SLC6A4-28L+ ++-(CPD, D17S2009, D17S2004)-D17S2120-ter. Both genes were deleted in one of 17 neurofibromatosis type 1 (NF1) patients carrying submicroscopic NF1 contiguous gene deletions.

Alteration of pulmonary neuroendocrine cells during epithelial repair of naphthalene-induced airway injury.

Whole-mount airway preparations isolated from the lungs of mice treated by intraperitoneal injection of naphthalene and allowed to recover for 5 days were examined for the distribution and abundance of solitary pulmonary neuroendocrine cells (PNECs) and neuroepithelial bodies (NEBs) along the main axial pathway of the right middle lobe. Sham mice treated with corn oil vehicle were examined in a similar manner. An antibody to calcitonin gene-related peptide, a neuroendocrine cell marker, was used to identify the location, size, and number of PNECs and NEBs in the airways. After naphthalene treatment and epithelial repair, NEBs were significantly increased along the walls of the airways as well as on branch point ridges. The surface area covered by NEBs composed of 20 or fewer PNECs was significantly enlarged after naphthalene treatment compared with control NEBs of an equivalent cell number. The PNEC number per square millimeter was also increased more than threefold above control values after naphthalene treatment. These findings provide further support for a key role of neuroendocrine cells in the reparative process of airway epithelial cell renewal after injury.

Bronchoscopic management of central airway obstruction.

OBJECTIVES: Patients with central airway obstruction are critically ill, with impending suffocation. They are seen with diverse anatomic and functional deficits caused by both benign and malignant obstructions. Such cases were reviewed to examine the indications, techniques, and outcomes of an algorithm approach to bronchoscopic management. METHODS: Between July 1992 and April 1996, 97 patients underwent bronchoscopic procedures for the management of central airway obstruction, and their cases were used for a retrospective review of the airway management. RESULTS: There were 48 male and 49 female patients, aged 13 to 85 years. There were 48 benign and 49 malignant pathologic conditions that gave rise to 108 stenoses. These were treated with 199 endoscopic procedures with an average of 1.7 interventions per endoscopy, including mechanical core-out (62), dilation (135), laser ablation (44), placement of brachytherapy catheters (9), and stent placement (88). Diagnoses included lung cancer, primary tracheobronchial tumors, tumors metastatic to the airway or mediastinum, and a variety of benign obstructions. In the group of 97 patients there were 2 (2%) perioperative deaths and 34 (34%) late deaths, 29 in the malignant group and 5 in the benign group. Median survival was 7.6 months (range 1 week-31 months). There were 7 (7%) complications among the group of 97, 4 in the malignant group, and 3 in the benign group. CONCLUSIONS: Endobronchial surgical techniques can be used safely and systematically for the relief of benign and malignant central airway obstructions; a diversity of approaches and interventions are required to produce and maintain palliation of airway symptoms.