A Pilot Randomized Clinical Trial of Base-in Relieving Prism Spectacle Treatment of Intermittent Exotropia.

SIGNIFICANCE: This pilot randomized trial, the first to evaluate a specific base-in relieving prism treatment strategy for childhood intermittent exotropia, did not support proceeding to a full-scale clinical trial. Defining and measuring prism adaptation in children with intermittent exotropia are challenging and need further study. PURPOSE: This study aimed to determine whether to proceed to a full-scale trial of relieving base-in prism spectacles versus refractive correction alone for children with intermittent exotropia. METHODS: Children 3 years old to those younger than 13 years with distance intermittent exotropia control score of ≥2 points on the Intermittent Exotropia Office Control Scale (Strabismus 2006;14:147-150; 0 [phoria] to 5 [constant]), ≥1 episode of spontaneous exotropia, and 16 to 35∆ by prism-and-alternate-cover test, who did not fully prism adapt on a 30-minute in-office prism-adaptation test were randomized to base-in relieving prism (40% of the larger of distance and near exodeviations) or nonprism spectacles for 8 weeks. A priori criteria to conduct a full-scale trial were defined for the adjusted treatment group difference in mean distance control: "proceed" (≥0.75 points favoring prism), "uncertain" (>0 to <0.75 points favoring prism), or "do not proceed" (≥0 points favoring nonprism). RESULTS: Fifty-seven children (mean age, 6.6 ± 2.2 years; mean baseline distance control, 3.5 points) received prism (n = 28) or nonprism (n = 29) spectacles. At 8 weeks, mean control values were 3.6 and 3.3 points in prism (n = 25) and nonprism (n = 25) groups, respectively, with an adjusted difference of 0.3 points (95% confidence interval, -0.5 to 1.1 points) favoring nonprism (meeting our a priori "do not proceed" criterion). CONCLUSIONS: Base-in prism spectacles, equal to 40% of the larger of the exodeviations at distance or near, worn for 8 weeks by 3- to 12-year-old children with intermittent exotropia did not yield better distance control than refractive correction alone, with the confidence interval indicating that a favorable effect of 0.75 points or larger is unlikely. There was insufficient evidence to warrant a full-scale randomized trial.

Prevalence, Prevention, and Treatment of Work-Related Musculoskeletal Disorders Among Microsurgeons.

BACKGROUND: While work related musculoskeletal disorders have been well recognized among all surgeons, and microsurgeons in particular; their prevention and treatment are presently unknown. Our study aims to define the impact of musculoskeletal ailments on microsurgeons and investigate trends in microsurgeon musculoskeletal injury treatment. METHODS: An electronic survey was sent to all members of the American Society of Reconstructive Microsurgery. The survey solicited surgeon demographics, microsurgical volume, equipment usage, history of musculoskeletal injury, impact of injury, and interventions / treatment modalities used to address / prevent these issues. RESULTS: Of the 883 microsurgeons surveyed, 203 responded (23% response rate). The average age was 45 years (IQR 39-52 years). Most microsurgeons were male (80.8%). Musculoskeletal injury or symptoms related to microsurgery were reported by 137 respondents (67.0%). Fifty surgeons (37.9%) reported that their musculoskeletal injury had adversely affected their practice. Formal medical intervention was sought by 53 respondents (26.1%), with 17 surgeons (8.4%) undergoing surgical intervention. Self-treated was used by 127 microsurgeons (62.6%) for musculoskeletal ailments. Preventative treatments such as strength training, stretching, yoga, massages, and diet were the most beneficial, each with utilization scores of 4 out of 5. CONCLUSION: A majority of microsurgeons experience musculoskeletal injury, and some even require surgery to treat their musculoskeletal pathology. Prophylactic practices such as strength training, stretching, yoga, massages, and diet maintenance, are the superior treatment for musculoskeletal injury. Microsurgeons should incorporate training routines in their lives as injury prophylaxis to improve their career longevity and patient care.

Estimation of Hemi-Abdominal-Based Free Flap Weight Using Two Computed Tomography-Derived Measurements.

BACKGROUND: Accurate flap weight estimation is crucial for preoperative planning in microsurgical breast reconstruction; however, current flap weight estimation methods are time consuming. It was our objective to develop a parsimonious and accurate formula for the estimation of abdominal-based free flap weight. METHODS: Patients who underwent hemi-abdominal-based free tissue transfer for breast reconstruction at a single institution were retrospectively reviewed. Subcutaneous tissue thicknesses were measured on axial computed tomography angiograms at several predetermined points. Multivariable linear regression was used to generate the parsimonious flap weight estimation model. Split-sample validation was used to for internal validation. RESULTS: A total of 132 patients (196 flaps) were analyzed, with a mean body mass index of 31.2 ± 4.0 kg/m2 (range: 22.6-40.7). The mean intraoperative flap weight was 990 ± 344 g (range: 368-2,808). The full predictive model (R 2 = 0.68) estimated flap weight using the Eq. 91.3x + 36.4y + 6.2z - 1030.0, where x is subcutaneous tissue thickness (cm) 5 cm lateral to midline at the level of the anterior superior iliac spine (ASIS), y is distance (cm) between the skin overlying each ASIS, and z is patient weight (kg). Two-thirds split-sample validation was performed using 131 flaps to build a model and the remaining 65 flaps for validation. Upon validation, we observed a median percent error of 10.2% (interquartile range [IQR]: 4.5-18.5) and a median absolute error of 108.6 g (IQR: 45.9-170.7). CONCLUSION: We developed and internally validated a simple and accurate formula for the preoperative estimation of hemi-abdominal-based free flap weight for breast reconstruction.

The Effect of Vibration on Pain During Intravenous Injection of Propofol: A Randomized Controlled Trial.

PURPOSE: Pain is a common side effect of intravenous injection of propofol. We conducted a randomized, prospective, single-blinded controlled trial to assess the efficacy of vibration analgesia on pain during propofol infusion in ambulatory surgery. METHODS: After institutional review board approval, 100 patients undergoing elective ambulatory surgery with general anesthesia were randomized into 2 groups. A control group (n = 50) consisted of patients who received infusion of propofol without vibration analgesia. A treatment group (n = 50) consisted of patients who received infusion of propofol with vibration analgesia using the Buzzy device. Pain was assessed using a 4-point pain manifestation scale scored by 2 independent, blinded observers. RESULTS: Participants in the treatment group with vibration analgesia were 0.47 times less likely (95% confidence interval, 0.24-0.94; P = 0.03) to experience any pain than the control group. The median summative pain score in the treatment group was significantly less than that of the control group [1 (interquartile range, 1-2) vs 2 (interquartile range, 2-4); P < 0.01] among participants who experienced any pain. Agreement between the 2 blinded observers regarding pain scores was excellent with κw = 0.82 (P < 0.001). Age, sex, body mass index, needle location or size, and medication doses did not differ significantly between the 2 groups. CONCLUSION: Vibration analgesia is an effective, low-risk modality that reduces the pain of intravenous propofol injection in general anesthesia.

Ergonomics Among Craniofacial Surgeons: A Survey of Work-Related Musculoskeletal Discomfort and Injury.

INTRODUCTION: Surgical procedures with loupe magnification, headlights, and microscopes expose craniofacial surgeons to mechanical stress that can increase risk of long-term musculoskeletal pain and injury. Identifying the prevalence and cause of work-related musculoskeletal discomfort may guide preventative strategies to prolong well-being, job satisfaction, and greater duration of surgical careers. METHODS: A 29-question online survey was distributed to the surgeon members of the American Cleft Palate-Craniofacial Association. Eight hundred seventy-three surveys were distributed, and the anonymous responses were recorded using Google forms. RESULTS: One hundred ninety-six unique responses were recorded (22.5% response rate). A total of 64.2% reported experiencing musculoskeletal symptoms during their career, with neck, lower back, and shoulders being the most common problem areas. Multivariate analysis demonstrated surgical loupes (odds ratio 2.36, P = 0.03) and length of surgical practice >15 years (odds ratio 1.95, P = 0.04) were independently associated with greater odds of developing symptoms. Headlights (median pain = 3, P < 0.001), loupes (median pain = 3.5, P < 0.001), and operative microscope use (median pain = 2, P = 0.02) were all associated with higher pain while operating. A total of 52.5% respondents sought medical treatments, 50.5% were concerned musculoskeletal discomfort would affect their careers, 56.6% reported a colleague that required an operation, and 30.2% reported a colleague on temporary or permanent disability. CONCLUSIONS: Craniofacial surgery often involves long procedures, use of surgical adjuncts, and ergonomically straining postures, which can lead to musculoskeletal discomfort and injury. This under-reported and important phenomenon merits candid conversation and active preventative strategies to prolong surgical careers, improve professional satisfaction, and maximize patient safety.

Gene therapy targeting cardiac phosphoinositide 3-kinase (p110α) attenuates cardiac remodeling in type 2 diabetes.

Diabetic cardiomyopathy is a distinct form of heart disease that represents a major cause of death and disability in diabetic patients, particularly, the more prevalent type 2 diabetes patient population. In the current study, we investigated whether administration of recombinant adeno-associated viral vectors carrying a constitutively active phosphoinositide 3-kinase (PI3K)(p110α) construct (rAAV6-caPI3K) at a clinically relevant time point attenuates diabetic cardiomyopathy in a preclinical type 2 diabetes (T2D) model. T2D was induced by a combination of a high-fat diet (42% energy intake from lipid) and low-dose streptozotocin (three consecutive intraperitoneal injections of 55 mg/kg body wt), and confirmed by increased body weight, mild hyperglycemia, and impaired glucose tolerance (all P < 0.05 vs. nondiabetic mice). After 18 wk of untreated diabetes, impaired left ventricular (LV) systolic dysfunction was evident, as confirmed by reduced fractional shortening and velocity of circumferential fiber shortening (Vcfc, all P < 0.01 vs. baseline measurement). A single tail vein injection of rAAV6-caPI3K gene therapy (2×1011vector genomes) was then administered. Mice were followed for an additional 8 wk before end point. A single injection of cardiac targeted rAAV6-caPI3K attenuated diabetes-induced cardiac remodeling by limiting cardiac fibrosis (reduced interstitial and perivascular collagen deposition, P < 0.01 vs. T2D mice) and cardiomyocyte hypertrophy (reduced cardiomyocyte size and Nppa gene expression, P < 0.001 and P < 0.05 vs. T2D mice, respectively). The diabetes-induced LV systolic dysfunction was reversed with rAAV6-caPI3K, as demonstrated by improved fractional shortening and velocity of circumferential fiber shortening (all P < 0.05 vs pre-AAV measurement). This cardioprotection occurred in combination with reduced LV reactive oxygen species (P < 0.05 vs. T2D mice) and an associated decrease in markers of endoplasmic reticulum stress (reduced Grp94 and Chop, all P < 0.05 vs. T2D mice). Together, our findings demonstrate that a cardiac-selective increase in PI3K(p110α), via rAAV6-caPI3K, attenuates T2D-induced diabetic cardiomyopathy, providing proof of concept for potential translation to the clinic.NEW & NOTEWORTHY Diabetes remains a major cause of death and disability worldwide (and its resultant heart failure burden), despite current care. The lack of existing management of heart failure in the context of the poorer prognosis of concomitant diabetes represents an unmet clinical need. In the present study, we now demonstrate that delayed intervention with PI3K gene therapy (rAAV6-caPI3K), administered as a single dose in mice with preexisting type 2 diabetes, attenuates several characteristics of diabetic cardiomyopathy, including diabetes-induced impairments in cardiac remodeling, oxidative stress, and function. Our discovery here contributes to the previous body of work, suggesting the cardioprotective effects of PI3K(p110α) could be a novel therapeutic approach to reduce the progression to heart failure and death in diabetes-affected patients.

Characterization of emissions from a pilot-scale combustor operating on coal blended with woody biomass.

Emissions generated from the combustion of coal have been a subject of regulation by the United States Environmental Protection Agency (U.S. EPA) and State agencies for years, as they have been associated with adverse effects on human health and the environment. Over the past several decades, regulations on these facility emissions have become more stringent and have therefore caused industry to look toward new pre- and post-combustion control technologies. In more recent years, there has been a "push" toward renewable and cleaner burning alternative fuels as replacements for traditional fossil fuels. Part of this "push" has been accomplished by States and Regions offering incentives and options for renewable portfolios, which over half of the states now have in some form. The current study investigates the potential changes in both gaseous and particulate emissions from the use of a variety of woody biomass materials as a drop-in replacement for coal as compared to use of 100% bituminous coal. Four different biomass materials are blended individually with coal at 20% and 40% by mass for testing on the U.S. EPA's Multi-Pollutant Control Research Facility, a pilot-scale coal-fired facility located in Research Triangle Park, North Carolina. Emissions are calculated based on measurements from the flue gas to characterize gaseous species (CO, CO2, NOX, SO2, other acid gases, and several organic hazardous air pollutants) as well as fine and ultrafine particulate (mass, size distribution, number count, elemental carbon, organic carbon, and black carbon) and compared among each combination of fuels and 100% bituminous coal.

Estimation of Profunda Artery Perforator Flap Weight Using Preoperative Computed Tomography Angiography.

BACKGROUND: Given the relatively small size of thigh-based flaps and the possible necessity for a multiflap reconstruction, it is imperative to arrive at an accurate estimation of flap weight during preoperative planning. It was our objective to develop a novel technique for the preoperative estimation of profunda artery perforator (PAP) flap weight. METHODS: All patients that underwent transverse PAP flap breast reconstruction at two institutions were retrospectively reviewed. Subcutaneous tissue thicknesses were measured on axial computed tomography angiography scans at several predetermined points. The distance from the inferior gluteal crease to the PAP was also recorded. Linear regression was used to estimate flap weight. RESULTS: A total of 18 patients (32 flaps) were analyzed. The median intraoperative flap weight was 299 g (interquartile range [IQR]: 235-408). The parsimonious model (R 2 = 0.80) estimated flap weight using the Eq. 77.9x + 33.8y + 43.4z - 254.3, where x is subcutaneous tissue thickness (cm) at the lateral border of long head of the biceps femoris at a level 4.5 cm caudal to the inferior gluteal fold, y is distance (cm) from the inferior gluteal fold to the dominant PAP, and z has a value of 1 if the patient was scanned in the supine position or 0 if prone. The aforementioned formula yielded a median estimated flap weight of 305 g (IQR: 234-402) and a median percent error of 10.5% (IQR: 6.1-16.2). CONCLUSION: The authors demonstrate a simple and accurate formula for the preoperative estimation of transverse PAP flap weight for breast reconstruction.

Development and Modification of an Outcome Measure to Follow Symptoms of Children with Sinusitis.

OBJECTIVE: To develop a parent-reported Pediatric Rhinosinusitis Symptom Scale (PRSS) that could be used to monitor symptoms of young children with acute sinusitis in response to therapy. STUDY DESIGN: We developed an 8-item symptom severity scale and evaluated its internal reliability, construct validity, and responsiveness in children 2-12 years of age with acute sinusitis. Parents of 258 children with acute sinusitis completed the PRSS at the time of diagnosis, as a diary at home, and at the follow-up visit at days 10-12. Based on psychometric results and additional parent feedback, we revised the scale. We evaluated the revised version in 185 children with acute sinusitis. RESULTS: Correlations between the scale and reference measures on the day of enrollment were in the expected direction and of the expected magnitude. PRSS scores at the time of presentation correlated with radiographic findings (P < .001), functional status (P < .001), and parental assessment of overall symptom severity (P < .001). Responsiveness (standardized response mean) and test-retest reliability of the revised scale were good (2.17 and 0.75, respectively). CONCLUSIONS: We have developed an outcome measure to track the symptoms of acute sinusitis. Data presented here support the use of the PRSS as a measure of change in symptom burden in clinical trials of children with acute sinusitis.

The evolution of abdominal microbiomes in fungus-growing ants.

The attine ants are a monophyletic lineage that switched to fungus farming ca. 55-60 MYA. They have become a model for the study of complex symbioses after additional fungal and bacterial symbionts were discovered, but their abdominal endosymbiotic bacteria remain largely unknown. Here, we present a comparative microbiome analysis of endosymbiotic bacteria spanning the entire phylogenetic tree. We show that, across 17 representative sympatric species from eight genera sampled in Panama, abdominal microbiomes are dominated by Mollicutes, α- and γ-Proteobacteria, and Actinobacteria. Bacterial abundances increase from basal to crown branches in the phylogeny reflecting a shift towards putative specialized and abundant abdominal microbiota after the ants domesticated gongylidia-bearing cultivars, but before the origin of industrial-scale farming based on leaf-cutting herbivory. This transition coincided with the ancestral single colonization event of Central/North America ca. 20 MYA, documented in a recent phylogenomic study showing that almost the entire crown group of the higher attine ants, including the leaf-cutting ants, evolved there and not in South America. Several bacterial species are located in gut tissues or abdominal organs of the evolutionarily derived, but not the basal attine ants. The composition of abdominal microbiomes appears to be affected by the presence/absence of defensive antibiotic-producing actinobacterial biofilms on the worker ants' cuticle, but the significance of this association remains unclear. The patterns of diversity, abundance and sensitivity of the abdominal microbiomes that we obtained explore novel territory in the comparative analysis of attine fungus farming symbioses and raise new questions for further in-depth research.

Defining the Zygomaticosphenoidal Angle as a Guide to Anatomic Zygomaticomaxillary Complex Fracture Reduction.

BACKGROUND: Alignment of the zygomaticosphenoid suture is fundamental to reduction of zygomaticomaxillary complex fractures. To prevent a rotational deformity, the correct angle of the zygoma relative to the cranial base must be restored. Clinically, this can be a challenge, especially when there is comminution of the zygomaticosphenoid suture. Defining a zygomaticosphenoidal angle would provide a reference for use with stereotactic navigation to achieve anatomic reduction. METHODS: A single-center retrospective analysis of 100 patients was designed to determine normative zygomaticosphenoidal angle values. An angle subtended by the midline and a best-fit line through the zygomaticosphenoid suture on axial computed tomography was measured bilaterally in patients with isolated mandibular or nasal fractures. The mean of this measurement for 3 vertically adjacent cuts was calculated with position of central cut determined by the equator of the globe and trigone of the sphenoid. Multivariate regression was completed to identify changes in zygomaticosphenoidal angle with age, sex, and race. RESULTS: The mean zygomaticosphenoidal angle was 47° (range 39°-55°). 97% of angles were within 2 standard deviations (8°) of mean. Regression analysis demonstrated no significant change in angle with age (P = 0.74) or sex (P = 0.89). For each angle, the variation across the 3 sample cuts was ≤4.5°. Patients demonstrated high fidelity in zygomaticosphenoidal angle bilaterally with mean difference of 3°. CONCLUSION: The zygomaticosphenoidal angle is a useful reference, in conjunction with stereotactic navigation, for reduction of zygomaticomaxillary complex fractures. Contralaterally obtained patient-specific data may be used to guide unilateral repair. Normative values may serve as reference in bilateral injury.

Patient-Reported Satisfaction and Quality of Life in Postmastectomy Radiated Patients: A Comparison between Delayed and Delayed Immediate Autologous Breast Reconstruction in a Predominantly Minority Patient Population.

BACKGROUND: Delayed immediate (DI) autologous breast reconstruction consists of immediate postmastectomy tissue expander placement, radiation therapy, and subsequent autologous reconstruction. The decision between timing of reconstructive methods is challenging and remains to be elucidated. We aim to compare patient reported outcomes and quality of life between delayed and DI reconstruction. METHODS: A retrospective review of all patients, who underwent autologous breast reconstruction at Montefiore Medical Center from January 2009 to December 2016, was conducted. Patients who underwent postmastectomy radiotherapy were divided into two cohorts: delayed and DI autologous breast reconstruction. Patients were mailed a BREAST-Q survey and their responses, demographic information, complications, and need for revisionary procedures were analyzed. RESULTS: A total of 79 patients met inclusion criteria: 34.2% (n = 27) in the delayed and 65.8% (n = 52) in the DI group. 77.2% (n = 61) of patients were a minority population. Patients in each cohort had similar baseline characteristics; however, the DI cohort was more likely to have bilateral reconstruction (46.2% [n = 24] vs. 7.4% [n = 2]; p = 0.0005) and to have major mastectomy flap necrosis (22.4% [n = 17] vs. 0.0% [n = 0]; p = 0.002). Premature tissue expander removal occurred in 17.3% (n = 9) of patients in the DI group. BREAST-Q response rates were 44.4% (n = 12) in the delayed group and 57.7% (n = 30) in the DI group. Responses showed similar satisfaction with their breasts, well-being, and overall outcome. CONCLUSION: Delayed and DI autologous breast reconstruction yield similar patient-reported satisfaction; however, patients undergoing DI reconstruction have higher rates of major mastectomy necrosis. Furthermore, patients in the DI group risk premature tissue expander removal.

Ecological specialization is associated with genetic structure in the ant-associated butterfly family Lycaenidae.

The role of specialization in diversification can be explored along two geological axes in the butterfly family Lycaenidae. In addition to variation in host-plant specialization normally exhibited by butterflies, the caterpillars of most Lycaenidae have symbioses with ants ranging from no interactions through to obligate and specific associations, increasing niche dimensionality in ant-associated taxa. Based on mitochondrial sequences from 8282 specimens from 967 species and 249 genera, we show that the degree of ecological specialization of lycaenid species is positively correlated with genetic divergence, haplotype diversity and an increase in isolation by distance. Nucleotide substitution rate is higher in carnivorous than phytophagous lycaenids. The effects documented here for both micro- and macroevolutionary processes could result from increased spatial segregation as a consequence of reduced connectivity in specialists, niche-based divergence or a combination of both. They could also provide an explanation for the extraordinary diversity of the Lycaenidae and, more generally, for diversity in groups of organisms with similar multi-dimensional ecological specialization.

Comparison of gaseous and particulate emissions from a pilot-scale combustor using three varieties of coal.

Gaseous and particulate emissions generated from the combustion of coal have been associated with adverse effects on human health and the environment, and have therefore been the subject of regulation by federal and state government agencies. Detailed emission characterizations are needed to better understand the impacts of pre- and post-combustion controls on a variety of coals found in the United States (U.S.). While the U.S. Environmental Protection Agency (EPA) requires industry reporting of emissions for criteria and several hazardous air pollutants (HAPs), many of the methods for monitoring and measuring these gaseous and particulate emissions rely on time-integrated sampling techniques. Though these emissions reports provide an overall representation of day-to-day operations, they represent well-controlled operations and do not encompass real combustion events that occur sporadically. The current study not only characterizes emissions from three coals (bituminous, sub-bituminous, and lignite), but also investigates the use of instrumentation for improved measurement and monitoring techniques that provide real-time, continuous emissions data. Testing was completed using the U.S. EPA's Multi-Pollutant Control Research Facility, a pilot-scale coal-fired combustor using industry-standard emission control technologies, in Research Triangle Park, North Carolina. Emissions were calculated based on measurements from the flue gas (pre- and post-electrostatic precipitator), to characterize gaseous species (CO, CO2, O2, NOX, SO2, other acid gases, and several organic HAPs) as well as fine and ultrafine particulate (mass, size distribution, number count, elemental carbon, organic carbon, and black carbon). Comparisons of traditional EPA methods to those made via Fourier Transfer Infrared (FTIR) Spectroscopy for CO, NOX, and SO2 are also reported.

Monitoring concentration and isotopic composition of methane in groundwater in the Utica Shale hydraulic fracturing region of Ohio.

Degradation of groundwater quality is a primary public concern in rural hydraulic fracturing areas. Previous studies have shown that natural gas methane (CH4) is present in groundwater near shale gas wells in the Marcellus Shale of Pennsylvania, but did not have pre-drilling baseline measurements. Here, we present the results of a free public water testing program in the Utica Shale of Ohio, where we measured CH4 concentration, CH4 stable isotopic composition, and pH and conductivity along temporal and spatial gradients of hydraulic fracturing activity. Dissolved CH4 ranged from 0.2 µg/L to 25 mg/L, and stable isotopic measurements indicated a predominantly biogenic carbonate reduction CH4 source. Radiocarbon dating of CH4 in combination with stable isotopic analysis of CH4 in three samples indicated that fossil C substrates are the source of CH4 in groundwater, with one 14C date indicative of modern biogenic carbonate reduction. We found no relationship between CH4 concentration or source in groundwater and proximity to active gas well sites. No significant changes in CH4 concentration, CH4 isotopic composition, pH, or conductivity in water wells were observed during the study period. These data indicate that high levels of biogenic CH4 can be present in groundwater wells independent of hydraulic fracturing activity and affirm the need for isotopic or other fingerprinting techniques for CH4 source identification. Continued monitoring of private drinking water wells is critical to ensure that groundwater quality is not altered as hydraulic fracturing activity continues in the region. Graphical abstract A shale gas well in rural Appalachian Ohio. Photo credit: Claire Botner.

Mobile Platform for Multiplexed Detection and Differentiation of Disease-Specific Nucleic Acid Sequences, Using Microfluidic Loop-Mediated Isothermal Amplification and Smartphone Detection.

New tools are needed to enable rapid detection, identification, and reporting of infectious viral and microbial pathogens in a wide variety of point-of-care applications that impact human and animal health. We report the design, construction, and characterization of a platform for multiplexed analysis of disease-specific DNA sequences that utilizes a smartphone camera as the sensor in conjunction with a hand-held "cradle" that interfaces the phone with a silicon-based microfluidic chip embedded within a credit-card-sized cartridge. Utilizing specific nucleic acid sequences for four equine respiratory pathogens as representative examples, we demonstrated the ability of the system to utilize a single 15 µL droplet of test sample to perform selective positive/negative determination of target sequences, including integrated experimental controls, in approximately 30 min. Our approach utilizes loop-mediated isothermal amplification (LAMP) reagents predeposited into distinct lanes of the microfluidic chip, which when exposed to target nucleic acid sequences from the test sample, generates fluorescent products that when excited by appropriately selected light emitting diodes (LEDs), are visualized and automatically analyzed by a software application running on the smartphone microprocessor. The system achieves detection limits comparable to those obtained by laboratory-based methods and instruments. Assay information is combined with the information from the cartridge and the patient to populate a cloud-based database for epidemiological reporting of test results.

The scientific and public-health imperative for a vaccine against dental caries.

Dental caries is caused by one of the most ubiquitous bacterial infections of humans. In many countries such as Brazil and China, this disease is reaching epidemic proportions, and it is clear that a more effective public-health measure to combat dental caries is needed, because disadvantaged children are the most severely affected. One of the main groups of oral microorganisms, the mutans streptococci, has been associated with the aetiology of dental caries, and preclinical studies of immunological interventions have shown the feasibility of interfering with this disease. Moreover, clinical trials have indicated that a mucosal immune response to a crucial antigen(s) of mutans streptococci can influence the pathogenesis of dental caries. Evidence that this antigen(s) is appropriate for use in a vaccine against dental caries, as well as evidence for an appropriate target population of individuals and a logical time of administration, has now emerged.

The Role of Proteomic Testing in Improving Prognosis And Care Planning Quality Measures for Lung Cancer.

PURPOSE: The Oncology Care Model (OCM) is a payment model from the Centers for Medicare and Medicaid Services designed to reduce costs and improve quality in cancer care. Key components of quality for the OCM originate from the 13-component cancer care plan. We surveyed the literature to understand the value of prognosis in OCM-directed planning for non-small-cell lung cancer (NSCLC) care and to investigate how the results of a prognostic, proteomic biomarker test, the VeriStrat test, can help OCM-participating providers meet the specific quality measures. DESIGN: A targeted literature review was supplemented by real-world author experience. METHODOLOGY: Available MEDLINE-indexed literature on the topic of lung cancer prognosis and cancer care planning (1997-2017) were reviewed. Authors also included relevant commentary based on their own real-world experience with VeriStrat testing and prognostic conversations. RESULTS: There was near-universal consensus in guidelines and literature about the critical importance of early, candid, and ongoing physician-patient discussions about prognosis, which informs most components of the OCM care plan. The VeriStrat test has been shown to provide accurate predictions of outcomes in all lines of therapy and in various treatments for patients with NSCLC, including chemotherapies and EGFR-TKI therapies. CONCLUSION: Accurate prognostic estimates, such as those provided by the VeriStrat test, are useful for predicting and documenting expected response to treatment, avoiding ineffective and costly overtreatment and for facilitating meaningful conversations with NSCLC patients about the timing of best supportive care and hospice care when appropriate, thereby improving cancer care planning and quality scores.

Going the distance: Mapping mobility in the Kalahari Desert during the Middle Stone Age through multi-site geochemical provenancing of silcrete artefacts.

This study utilises geochemical provenancing of silcrete raw materials, in combination with chaîne opératoire analyses, to explore lithic procurement and behavioural patterns in the northern Kalahari Desert during the Middle Stone Age (MSA). New data from the sites of Rhino Cave, Corner Cave, and ≠Gi in northwest Botswana, combined with earlier results from White Paintings Shelter, reveal that the long distance transport of silcrete for stone tool manufacture was a repeated and extensively used behaviour in this region. Silcrete was imported over distances of up to 295 km to all four sites, from locations along the Boteti River and around Lake Ngami. Significantly, closer known sources of silcrete of equivalent quality were largely bypassed. Silcrete artefacts were transported at various stages of production (as partially and fully prepared cores, blanks, and finished tools) and, with the exception of ≠Gi, in large volumes. The import occurred despite the abundance of locally available raw materials, which were also used to manufacture the same tool types. On the basis of regional palaeoenvironmental data, the timing of the majority of silcrete import from the Boteti River and Lake Ngami is constrained to regionally drier periods of the MSA. The results of our investigation challenge key assumptions underlying predictive models of human mobility that use distance-decay curves and drop-off rates. Middle Stone Age peoples in the Kalahari appear to have been more mobile than anticipated, and repeatedly made costly choices with regard to both raw material selection and items to be transported. We conclude that (i) base transport cost has been overemphasised as a restrictive factor in predictive models, and (ii) factors such as source availability and preference, raw material quality, and potential sociocultural influences significantly shaped prehistoric landscape use choices.

Eavesdropping on cooperative communication within an ant-butterfly mutualism.

Signalling is necessary for the maintenance of interspecific mutualisms but is vulnerable to exploitation by eavesdropping. While eavesdropping of intraspecific signals has been studied extensively, such exploitation of interspecific signals has not been widely documented. The juvenile stages of the Australian lycaenid butterfly, Jalmenus evagoras, form an obligate association with several species of attendant ants, including Iridomyrmex mayri. Ants protect the caterpillars and pupae, and in return are rewarded with nutritious secretions. Female and male adult butterflies use ants as signals for oviposition and mate searching, respectively. Our experiments reveal that two natural enemies of J. evagoras, araneid spiders and braconid parasitoid wasps, exploit ant signals as cues for increasing their foraging and oviposition success, respectively. Intriguingly, selection through eavesdropping is unlikely to modify the ant signal.