Shell temperature: How shall we tell if a still gosling is under the eggshell?

The present investigation was aimed at predicting a still (i.e., dead) vs. live embryo within a hatching goose egg by measuring the eggshell cooling rate. For this, we daily measured the temperature (T) values on the shell surface of goose eggs after they were removed from the incubator and during further natural cooling. T was recorded every 0.5 h for further 1.5 h of cooling. It was possible to recognize eggs with dead embryos using the combination of T, egg weight (W), and surface area (S). The resultant indicator (TS/W) was called specific temperature index (STI). The mathematical relationship using STI measurements between Days 8-13 facilitated 80 % correct identification of the eggs with dead embryos. Additionally, we derived mathematical dependencies for shell weight (Ws) and thickness (t) by utilizing the values of W, egg volume (V), S, the average T of all measurements taken, as well as the drop in T during 1.5 h of natural cooling. The key advantage of these parameters was their measurement and/or calculation by applying non-destructive methods. The integrated application of these parameters resulted in achieving high calculation accuracy as judged by correlation coefficients of 0.908 for Ws and 0.593 for t. These novel mathematical models have the potential to decrease hatching waste by predicting embryo viability. Our research will add to a toolkit for non-invasive egg assessment that is useful in the poultry industry, research on eggs, and engineering.

NKX2­1 copy number alterations are associated with oncogenic, immunological and prognostic remodeling in non­small cell lung cancer.

NK2 homeobox 1 (NKX2-1) copy number alterations (CNAs) are frequently observed in lung cancer. However, little is known about the complete landscape of focal alterations in NKX2-1 copy number (CN), their clinical significance and their therapeutic implications in non-small cell lung cancer (NSCLC). The correlations between NKX2-1 expression and EGFR driver mutations and programmed death ligand 1 (PD-L1) co-expression were studied using immunohistochemistry and PCR from the tumors of recruited Filipino patients (n=45). Clinical features of NSCLC with NKX2-1 CNAs were resolved at the tumor and clonal levels using the molecular profiles of patients with lung adenocarcinoma and lung squamous cell carcinoma from The Cancer Genome Atlas (n=1,130), and deconvoluted single-cell RNA-seq data from the Bivona project (n=1,654), respectively. Despite a significant and positive correlation between expression and CN (r=0.264; P<0.001), NKX2-1 CNAs exerted a stronger influence on the combined EGFR and PD-L1 status of NSCLC tumors than expression. NKX2-1 CN gain was prognostic of favorable survival (P=0.018) and a better response to targeted therapy. NKX2-1 CN loss predicted a worse survival (P=0.041). Mutational architecture in the Y-chromosome differentiated the two prognostic groups. There were 19,941 synonymous mutations and 1,408 genome-wide CN perturbations associated with NKX2-1 CNAs. Tumors with NKX2-1 CN gain expressed lymphocyte markers more heterogeneously than those with CN loss. Higher expression of tumor-infiltrating lymphocyte gene signatures in CN gain was prognostic of longer disease-free survival (P=0.005). Tumors with NKX2-1 CN gain had higher B-cell (P<0.001) and total T-cell estimates (P=0.003). NKX2-1 CN loss was associated with immunologically colder tumors due to higher M2 macrophage infiltrates (P=0.011) and higher expression of immune checkpoint proteins, CD274 (P=0.025), VTCN1 (P<0.001) and LGALS9 (P=0.002). In conclusion, NKX2-1 CNAs are associated with tumors that exhibit clinically diverse characteristics, and with unique oncogenic, immunological and prognostic signatures.

The differential prognostic implications of PD-L1 expression in the outcomes of Filipinos with EGFR-mutant NSCLC treated with tyrosine kinase inhibitors.

Background: The tumor immune microenvironment influences tumor evolution in non-small cell lung cancer (NSCLC). Yet, the prognostic value of programmed death-ligand 1 (PD-L1) in epidermal growth factor receptor (EGFR)-mutant NSCLC remains controversial. Additionally, prognostic studies in Filipinos with EGFR-mutant NSCLC remain unexplored to this day. Methods: We prospectively studied the outcomes of EGFR-mutant NSCLC in Filipino cohort, and retrospectively verified the survival trend using The Cancer Genome Atlas (TCGA) cohort. Kaplan-Meier method and generalized linear regression were used to assess survival. Expression and DNA methylation of cluster of differentiation 274 (CD274, gene that codes for PD-L1) were examined from TCGA tumor profiles. Pearson's correlation was used to correlate PD-L1 expression with outcomes associated with occurrence of EGFR mutations, tyrosine kinase inhibitor (TKI) types, and programmed cell death protein 1 (PD-1) expression. Proteome network analysis was used to examine the correlation between drug resistance and PD-L1. Results: PD-L1 positivity was associated with significantly longer progression-free survival (PFS; P=0.0096) but had a significantly contrasting influence in the overall survival (OS; P=0.0011). PD-L1 positivity (in both protein and RNA) was associated with longer median OS (mOS) in exon21 L858R, whereas, negativity was associated with longer mOS in exon19 deletion (exon19del). Stratification (high, low, negative) of PD-L1 expression lacked significant prognostic value (all P>0.05). PD-L1/CD274 expression (P<0.05) and DNA methylation (P<0.001) vary significantly among NSCLC subtypes and in different disease stages. Erlotinib treatment produced the longest median progression-free survival (mPFS; 874 days) relative to other EGFR-TKIs (137-311 days). PD-L1 lacked a significant correlation with EGFR-TKIs. Consistent with the immune-regulation activities of PD-1, higher expression leads to relatively shorter mOS. PD-1 correlated positively with PD-L1 expression and occurrence of exon21 L858R. Conclusions: PD-L1 differentially influenced the outcomes of Filipinos with EGFR-mutant NSCLC. NSCLC subtypes, disease stage, and PD-1 expression may impact the collective outcomes associated with PD-L1 and EGFR-sensitizing mutations.

Improved Digital Therapy for Developmental Pediatrics Using Domain-Specific Artificial Intelligence: Machine Learning Study.

BACKGROUND: Automated emotion classification could aid those who struggle to recognize emotions, including children with developmental behavioral conditions such as autism. However, most computer vision emotion recognition models are trained on adult emotion and therefore underperform when applied to child faces. OBJECTIVE: We designed a strategy to gamify the collection and labeling of child emotion-enriched images to boost the performance of automatic child emotion recognition models to a level closer to what will be needed for digital health care approaches. METHODS: We leveraged our prototype therapeutic smartphone game, GuessWhat, which was designed in large part for children with developmental and behavioral conditions, to gamify the secure collection of video data of children expressing a variety of emotions prompted by the game. Independently, we created a secure web interface to gamify the human labeling effort, called HollywoodSquares, tailored for use by any qualified labeler. We gathered and labeled 2155 videos, 39,968 emotion frames, and 106,001 labels on all images. With this drastically expanded pediatric emotion-centric database (>30 times larger than existing public pediatric emotion data sets), we trained a convolutional neural network (CNN) computer vision classifier of happy, sad, surprised, fearful, angry, disgust, and neutral expressions evoked by children. RESULTS: The classifier achieved a 66.9% balanced accuracy and 67.4% F1-score on the entirety of the Child Affective Facial Expression (CAFE) as well as a 79.1% balanced accuracy and 78% F1-score on CAFE Subset A, a subset containing at least 60% human agreement on emotions labels. This performance is at least 10% higher than all previously developed classifiers evaluated against CAFE, the best of which reached a 56% balanced accuracy even when combining "anger" and "disgust" into a single class. CONCLUSIONS: This work validates that mobile games designed for pediatric therapies can generate high volumes of domain-relevant data sets to train state-of-the-art classifiers to perform tasks helpful to precision health efforts.

A Mobile Game Platform for Improving Social Communication in Children with Autism: A Feasibility Study.

BACKGROUND: Many children with autism cannot receive timely in-person diagnosis and therapy, especially in situations where access is limited by geography, socioeconomics, or global health concerns such as the current COVD-19 pandemic. Mobile solutions that work outside of traditional clinical environments can safeguard against gaps in access to quality care. OBJECTIVE: The aim of the study is to examine the engagement level and therapeutic feasibility of a mobile game platform for children with autism. METHODS: We designed a mobile application, GuessWhat, which, in its current form, delivers game-based therapy to children aged 3 to 12 in home settings through a smartphone. The phone, held by a caregiver on their forehead, displays one of a range of appropriate and therapeutically relevant prompts (e.g., a surprised face) that the child must recognize and mimic sufficiently to allow the caregiver to guess what is being imitated and proceed to the next prompt. Each game runs for 90 seconds to create a robust social exchange between the child and the caregiver. RESULTS: We examined the therapeutic feasibility of GuessWhat in 72 children (75% male, average age 8 years 2 months) with autism who were asked to play the game for three 90-second sessions per day, 3 days per week, for a total of 4 weeks. The group showed significant improvements in Social Responsiveness Score-2 (SRS-2) total (3.97, p <0.001) and Vineland Adaptive Behavior Scales-II (VABS-II) socialization standard (5.27, p = 0.002) scores. CONCLUSION: The results support that the GuessWhat mobile game is a viable approach for efficacious treatment of autism and further support the possibility that the game can be used in natural settings to increase access to treatment when barriers to care exist.

The cow-calf relationship: from maternal responsiveness to the maternal bond and the possibilities for fostering.

The relationship between the cow and calf develops over time after birth. The behavioural mechanisms underlying its development are important and comparisons with other species may increase our understanding. In nature the cow will separate herself from the herd to give birth and then the cow-calf relationship will develop with the ability to recognise each other. While twinning levels are low in cows, they do rear their twin calves. If the calf is lost at or after birth the cow can be responsive towards other calves and in specific circumstances the cow can develop a maternal bond with an alien calf, i.e. foster. In this Research Reflection a distinction is made between the development of, on the one hand, maternal responsiveness (the tendency of the cow to care for a calf which occurs before birth) and, on the other hand, the development of the maternal-filial bond or relationship which is reciprocal, occurs after birth and is characterised by the ability to discriminate the mother's own calf from alien calves. These processes can overlap and the relationship between cow and calf in this 'hider' species is more plastic than in some other mammals. For example, a cow might form an attachment with an alien calf before she gives birth. After the cow has given birth the loss of her own calf may result in the state of maternal responsiveness being maintained, such that developing a maternal bond with one or several appropriate alien calves is possible. Viable fostering techniques are possible. If a maternal relationship to the mother's own calf has developed then fostering will be more difficult. If the cow's relationship with her own calf is not exclusive, and she is in a state of maternal responsiveness then fostering of calves of an appropriate age and status can be achieved.

On ground truth in cross-border ozone transport.

Cross-border transport of ozone is one of the most contentious issues of air pollution management in the U.S. Yet, both the modeling and observational studies are lacking. Models are normally validated by comparing predicted and observed ozone concentrations. However, proper validation of cross-border transport model requires a comparison of predictions against observation-based benchmarks of cross-border ozone transport. Such benchmarks are unavailable, as published observation-based studies always deal only with a combination of local production and cross-border transport, not a cross-border transport itself. We show how to extract necessary benchmarks from observations of rural monitoring sites near state borders. On example of the western border of New York, we find that in about two-thirds of the most polluted days all the ozone came in a steady cross-border inflow after previously passing over one or more large urban areas to the west. In all the enumerated days with direct cross-border inflow, daily maximum 8-hr concentrations of ozone just upwind of the border were over 60 ppb, with an average value of 68 ppb, just short of the 70 ppb ozone regulatory threshold, information also useful to state air pollution authorities. Implications: The purpose of the cross-border ozone pollution models is to predict cross-border transport of ozone, so the ability of the model to accurately represent observed ozone concentrations is necessary but not sufficient for model validation. The accuracy of predicted ozone concentrations is not necessarily the same as the accuracy of the predictions of ozone transport. Proper model validation requires comparisons against observation-based benchmarks of cross-border transport. Such observations, so far absent, can be obtained from rural monitoring sites near state borders, as illustrated by the example of western New York.

Position Statement of the Israeli Society for Musculoskeletal Medicine on Intramuscular Stimulation for Myofascial Pain Syndrome-A Delphi Process.

OBJECTIVE: To develop consensus on a position paper on the use of intramuscular stimulation (IMS) for the treatment of myofascial pain syndrome (MPS) by physicians in Israel. METHODS: The Israeli Society of Musculoskeletal Medicine ran a modified Delphi process to gather opinions from a multidisciplinary expert panel. Eight experts in the treatment of MPS were chosen and asked to participate, and six participated. The position paper was iterated three times. RESULTS: After three iterations, general consensus was reached by all six experts. The general statement that was agreed on was: "IMS is one of the preferred treatments for myofascial pain syndrome. The treatment is evidence-based, effective, safe, and inexpensive. The position of the Israeli Society of Musculoskeletal Medicine is that the treatment should be taught and used by all primary care physicians and those physicians in other areas of medicine who deal with pain in their work." CONCLUSIONS: The position paper is a basis for clinical work and education programs for physicians interested in a better understanding and ability to treat patients with a musculoskeletal complaint or manifestation of disease.

Triple-yolked eggs in domestic ducks: a rare occurrence.

Multiple-yolked avian eggs, and especially triple-yolked (TY) eggs, are rare. Over two years, 48,224 duck eggs (Anas platyrhynchos domesticus) were individually candled and seven (0.0145%) TY eggs were identified in a commercial breeding and incubation environment. When compared with double-yolked eggs (Salamon and Kent,2016) their mean weight, length, width and shape index did not differ, but their dimensions were greater than for single-yolked duck eggs. Yolk fertility in the TY eggs was low (33.33%), and this was attributed to smaller yolk size and early ovulation and/or follicle immaturity. By day 8 of incubation, fertile yolks were positioned next to the airspace. Egg 5 contained one fertile yolk, and the embryo developed to enter the airspace, was consuming all three yolks, but failed to hatch.

Yolk size and ovulation order determine fertility within double-yolked duck (Anas platyrhynchos domesticus) eggs.

Herein we examined the effects of yolk size and ovulation order on the fertilisation of yolks within double-yolked (DY) duck eggs. Single-yolked (SY) duck eggs had high fertility (89.98%), whereas in DY duck eggs fertility was low (51.9% yolks). The yolks closer to the airspace (Yolk 1) in DY eggs had higher fertility (68.82% vs 34.98% for Yolk 2; P<0.001). When only one of the two yolks was fertilised, Yolk 1 was fertilised in 99.12% of those eggs. Yolk 1 is presumed to be the first ovulated. The higher fertility of Yolk 1 is consistent with a primacy effect where the first ovulation has a higher probability of achieving fertilisation. Small DY eggs within the normal SY egg weight range (75-104.9g) had significantly lower yolk fertility (47.91%; n=550) compared with large (≥105g) DY eggs (54.56%; n=768; P<0.001). Yolk 1 fertility was lower in small compared with large DY eggs (64.18% vs 72.14%, respectively; P=0.003). Although Yolk 2 fertility was low, it was not affected by egg size. DY eggs with zero fertilised yolks were significantly lighter than DY eggs with one (P=0.007) or two (P<0.001) fertilised yolks (i.e. larger DY eggs were more likely to have fertilised yolks). Larger eggs (≥105g) have larger yolks and the evidence here shows that an optimal yolk size is a significant positive factor in achieving fertilization by dislodging spermatozoa, after ovulation, from their storage sites.

Efficacy of dry needling for treatment of myofascial pain syndrome.

Myofascial pain is a major cause of musculoskeletal regional pain. Myofascial pain, which is a high-prevalence but eminently treatable condition, is almost universally underdiagnosed by physicians and undertreated by physical therapy modalities. Large numbers of patients can be left suffering in chronic pain for years. Dry needling, also referred to as Intramuscular Stimulation, is a method in the arsenal of pain management which has been known for almost 200 years in Western medicine, yet has been almost completely ignored. With the increase in research in this field over the past two decades, there are many high-quality studies that demonstrate dry needling to be an effective and safe method for the treatment of myofascial pain when diagnosed and treated by adequately-trained physicians or physical therapists. This article provides an overview of recent literature regarding the treatment of myofascial pain syndrome, evidence for the efficacy of dry needling as a central component of its management, and a glimpse at developments in recent imaging methods to aid in the treatment of these problems.

Pedigree-based random effect tests to screen gene pathways.

The new generation of sequencing platforms opens new horizons in the genetics field. It is possible to exhaustively assay all genetic variants in an individual and search for phenotypic associations. The whole genome sequencing approach, when applied to a large human sample like the San Antonio Family Study, detects a very large number (>25 million) of single nucleotide variants along with other more complex variants. The analytical challenges imposed by this number of variants are formidable, suggesting that methods are needed to reduce the overall number of statistical tests. In this study, we develop a single degree-of-freedom test of variants in a gene pathway employing a random effect model that uses an empirical pathway-specific genetic relationship matrix as the focal covariance kernel. The empirical pathway-specific genetic relationship uses all variants (or a chosen subset) from gene members of a given biological pathway. Using SOLAR's pedigree-based variance components modeling, which also allows for arbitrary fixed effects, such as principal components, to deal with latent population structure, we employ a likelihood ratio test of the pathway-specific genetic relationship matrix model. We examine all gene pathways in KEGG database gene pathways using our method in the first replicate of the Genetic Analysis Workshop 18 simulation of systolic blood pressure. Our random effect approach was able to detect true association signals in causal gene pathways. Those pathways could be easily be further dissected by the independent analysis of all markers.

Chicks change their pecking behaviour towards stationary and mobile food sources over the first 12 weeks of life: improvement and discontinuities.

Chicks (Gallus gallus domesticus) learn to peck soon after hatching and then peck in rapid bursts or bouts with intervals of non-pecking activity. The food sources may be static such as seeds and chick crumb, or mobile such as a mealworm. Here, changes with age in pecking toward chick crumb and a mealworm were measured. Chicks were reared in pairs and their pecking of crumb food was video recorded in their pair housed environment, from food presentation, every third day from day 8 (wk 2) to day 65 (wk 10). Peck rate at crumb food reached maximum levels at day 32 (wk 5), and then declined, fitting a quadratic model, with no sex, sex of cagemate, or box order effects. Within bouts the peck rate was higher and it increased to day 41 (wk 6) and then declined, and here males pecked faster than females. A change in dietary protein concentration from 22% to 18% at day 28 (wk 4) had no effect on subsequent peck rate. Pecking at and consumption of a mealworm in pair housed chicks were measured weekly from wks [5 to 12]. The latency to first worm peck and latency to swallow decreased to wk 8 and increased thereafter. The peck rate to first wormpeck and number of pecks to swallow increased to wk 8 and then declined paralleling the changes with crumb food. The increase in peck rate is coupled with an increase in efficiency in worm catching. The results are consistent with the view that the improvement in pecking ability and accuracy compliments change in nutritional requirement best served by an invertebrate food (IF) source requiring speed to achieve feeding success, especially with live prey. When this food source is no longer crucial these associated skill levels decline. An appreciation of the role of domestic fowl in controlling insect populations, at farm level, that are often vectors in disease spread is lacking.

Survey of staff attitudes to the smoking ban in a medium secure unit.

AIMS AND METHODS: The aim of this survey was to explore staff attitudes to the indoor smoking ban in a medium secure unit and to ascertain if they had experienced any difficulties in imposing the ban in the four months after its introduction. All staff members available on duty who agreed to participate in the survey were interviewed using a semi-structured questionnaire. RESULTS: The response rate was 65%. Sixty-four percent of the staff supported the smoking ban. Forty-three percent reported experiencing patient management problems with the majority complaining of increased patient aggression, increased use of staff time in supervising patients smoking. Additionally, supervising staff were still being exposed to passive smoking. Sixty-five percent reported positive effects due to the ban with the majority reporting that patients were sleeping at night due to the smoking area being closed at night. CLINICAL IMPLICATIONS: A significant proportion of the staff is still opposed to the smoking ban. Changing staff attitudes through educational programmes will be important in ensuring success of a possible future total ban in psychiatric units.

Testosterone: from initiating change to modulating social organisation in domestic fowl (Gallus gallus domesticus).

Testosterone (T) concentrations in many species are sensitive to seasonal changes and to changes in social conditions. However, the effect of the natural or endogenous T increase in the juvenile on their social behaviour is not well understood. In this study, T and behaviour were measured from the pro-social juvenile to the adult stage in semi-feral domestic fowl. During the pro-social phase T levels and the distance chicks maintained between each other, i.e. inter-individual distance (IID) were low. Then, as T increased, a corresponding increase in IID occurred and continued in males until dispersal to individual adult male territories. In the new and initially stable adult social structure, T declined and IID remained high, indicating a new behavioural mechanism was in place. Males first mated as T levels were declining. They were then challenged; then T increased, and then IID increased again. Adult male T levels fluctuate, being low or declining in a socially stable environment and increasing following a challenge, suggesting a regulatory or modulating role for T. The results are consistent with T having an endogenous role: in the juvenile, driving behavioural change towards adulthood, and in adulthood, a modulating role regulating social organisation.

Characterization of the physiological spaces and distribution of tolbutamide in the perfused rat pancreas.

PURPOSE: To set up and validate a viable perfused rat pancreas model suitable for pharmacokinetic studies. MATERIALS AND METHODS: We setup and conducted multiple indicator dilution studies in the single pass perfused rat pancreas. The distribution of the reference markers [99mTc]-red blood cells (RBC), [14C]-sucrose, and [3H]-water, and tolbutamide were analysed using both non-parametric and parametric methods. RESULTS: The perfusion preparation was observed to be viable by oxygen consumption, outflow perfusate pH, lactate release and insulin release in response to glucose. Parametric analysis of the outflow profiles suggested that the transport of water and tolbutamide from the vascular space was permeability limited. Parametric and nonparametric estimates of Vd for RBC and sucrose were similar and were 0.14+/-0.01, 0.15 0.005 and 0.35+/-0.01 ml/g. The parametric estimate for water, 1.04+/-0.05 ml/g was greater than the nonparametric estimate, 0.89+/-0.02 ml/g. The multiple indicator dilution method Vd of tolbutamide of 0.75+0.08 ml/g was similar to the reported value of 0.73+/-0.04 ml/g estimated by tissue partitioning studies. CONCLUSIONS: A viable single pass pancreas perfusion model was established and applied to define distribution spaces of reference markers and the distribution kinetics of tolbutamide.

Resorbable plates for the fixation of mandibular fractures: a prospective study.

PURPOSE: The hypothesis for this prospective evaluation is that resorbable plates are equal to the performance of titanium 2-mm plates, regarding healing of the fracture with bone union and restoration of function. To prove this hypothesis, specific end points will be compared with literature norms for titanium 2-mm miniplate rigid fixation. The primary end point variable for this analysis is the union of the fracture and return to normal function. Secondary end point variables included the incidence of complications such as infection, malunion with malocclusion, soft tissue dehiscence, the need for revision surgery, specific technical challenges, operative time, and the learning curve for the surgeon. PATIENTS AND METHODS: This prospective study consisted of a sequential enrollment of 50 fractures that met the inclusion criteria of having a fracture of the mandibular body, symphysis, angle, or ramus, and required an open reduction and internal fixation for stabilization and repair. The resorbable plates and screws used consisted of an amorphous injection molded copolymer of L-lactide/D-lactide/trimethylene carbonate (Inion CPS system, Tampere, Finland). Data were collated and compared with literature norms for titanium plates and also compared with nonrigid fixation data from a prospective study performed on a similar population in the same institution. RESULTS: Clinical and radiographic evaluation indicated union of all fractures at the eighth follow-up visit. Three sites (6%) noted to have clinical signs of infection were treated immediately upon presentation, with fracture union by 8 weeks. There was no need for revision surgery in this series of patients; 12 screw heads fractured during screw placement and were immediately replaced without significant fracture sequelae. CONCLUSION: Based on this limited series of patients, the hypothesis formulated for this study was validated.