All fiber watt-level fiber source at 760†nm generated through four-wave mixing in a photonic crystal fiber.

There are limited fiber-based single-mode laser sources over the visible and near infrared range. Nonlinear conversion through four-wave mixing in photonic crystal fibers allows for the generation of new wavelengths far from a pump wavelength. Utilizing an all-fiber spliced configuration, we convert 1064 nm light into a W-level signal in the 750 nm - 820 nm spectral region. We demonstrate over 7.9 watts in the signal band, out of a custom photonic crystal fiber with M2 < 1.15. The input peak power as well as fiber length can be selected to keep the converted power in a 0.6 nm narrow emission band or broaden the output to 45 nm spectral band with spectral density greater than 50 mW/nm by pumping with higher peak powers.

Transcriptional changes detected in fecal RNA from neonatal dairy calves of different breeds following gastrointestinal disease of varying severity.

Gastrointestinal (GI) disease is a major health concern in preweaned dairy calves. The objective of this fixed cohort study was to use RNA isolated from preweaned Holstein and Jersey heifer calf feces to study the molecular adaptations to variable clinical GI disease. The study was conducted on a commercial calf ranch in the western U.S. Enrolled calves were assessed twice daily for variations in demeanor, milk intake, and hydration. Fecal consistency scores were recorded at enrollment (day 1), and on the day (day 10) that a fecal sample was collected for differential gene expression (DGE). Calves with diarrhea on either day were classified as having either uncomplicated, localized GI disease (scours), or systemic GI disease (systemic enteritis). Eighty-four calves' fecal RNA was evaluated for DGE, of which 33 calves (n = 20 Holstein; n = 13 Jersey) were consistently healthy. The remaining 51 calves (n = 23 Holstein; n = 28 Jersey) experienced varying severity of GI disease during the sampling window. Genes of interest were related to the inflammatory response (i.e., IFNG, NFKB1, NOD2, TLR2, and TLR4) and cell membrane or cytoplasmic transport (i.e., AQP3, FABP2, KRT8 and SLC5A1). Breed-specific findings indicated that AQP3, IFNG, and TLR4 were upregulated in Holsteins with systemic enteritis, whereas KRT8 was downregulated in systemically affected Jerseys. Holsteins did not appear affected by scours aside from a tendency for DGE of toll-like receptors (TLRs) on the day of diarrhea. However, Jersey calves consistently demonstrated a tendency to upregulate IFNG, NFKB1, and TLR4 when affected with either scours or systemic enteritis. These findings were more pronounced in systemically affected Jersey calves and were observed as a delayed response to both scours and systemic enteritis. These findings support previous observations suggesting that Holstein calves may be better equipped than Jersey calves to rapidly fight pathogen invasion.

Implementation of a collaborative online international learning program in nursing education: protocol for a mixed methods study.

BACKGROUND: An essential component of becoming a professional nurse is a perspective of global health issues and an awareness of diverse populations. Collaborative online international learning (COIL) using digital technologies, offers meaningful and rewarding opportunities to develop international partnerships between nurses from other countries, without economic, organisational or geographical barriers. Despite reported advantages of using COIL, few COIL interventions have been identified in the nursing literature. The aims of this study are to develop, implement and evaluate a COIL program between Australian and Canadian pre-registration nursing students. METHODS: The study will utilize a mixed methods approach incorporating pre and post-test surveys, focus groups, and semi-structured interviews of key stakeholders. The design will adhere to The State University of New York (SUNY) COIL's criteria for intercultural/international learning opportunities. Participants will be recruited from nursing programs at an Australian Training and Further Education Institute and a Canadian college. Bennett's stages of intercultural competence will provide the theoretical framework for the research. Four specific research interventions will be developed for this project. For students, there will be an online virtual community to allow students and teachers to communicate, socially connect and share resources with each other. Virtual reality simulations will be employed within a virtual global classroom to promote collaborative, intercultural learning. For faculty, a virtual community of practice will provide a platform for faculty to share education and research ideas and participate in collaborate research opportunities. DISCUSSION: This study will evaluate the outcomes of a nursing COIL program. It will measure participants' views on COIL, its contribution to student learning, changes in cultural awareness, organisational impact and research productivity. It will provide nursing students with the opportunity to become global leaders in nursing care and for faculty to develop international research skills and outputs. The findings from the study will allow further refinement of future nursing COIL programs.

Prediction of impending central-line-associated bloodstream infections in hospitalized cardiac patients: development and testing of a machine-learning model.

BACKGROUND: While modelling of central-line-associated blood stream infection (CLABSI) risk factors is common, models that predict an impending CLABSI in real time are lacking. AIM: To build a prediction model which identifies patients who will develop a CLABSI in the ensuing 24 h. METHODS: We collected variables potentially related to infection identification in all patients admitted to the cardiac intensive care unit or cardiac ward at Boston Children's Hospital in whom a central venous catheter (CVC) was in place between January 2010 and August 2020, excluding those with a diagnosis of bacterial endocarditis. We created models predicting whether a patient would develop CLABSI in the ensuing 24 h. We assessed model performance based on area under the curve (AUC), sensitivity and false-positive rate (FPR) of models run on an independent testing set (40%). FINDINGS: A total of 104,035 patient-days and 139,662 line-days corresponding to 7468 unique patients were included in the analysis. There were 399 positive blood cultures (0.38%), most commonly with Staphylococcus aureus (23% of infections). Major predictors included a prior history of infection, elevated maximum heart rate, elevated maximum temperature, elevated C-reactive protein, exposure to parenteral nutrition and use of alteplase for CVC clearance. The model identified 25% of positive cultures with an FPR of 0.11% (AUC = 0.82). CONCLUSIONS: A machine-learning model can be used to predict 25% of patients with impending CLABSI with only 1.1/1000 of these predictions being incorrect. Once prospectively validated, this tool may allow for early treatment or prevention.

Adaptive pressure-driven multi-criteria spatial decision-making for a targeted placement of green and grey runoff control infrastructures.

Traditional runoff control measures ignore the spatial imbalance of regional pressures, thereby failing to achieve a site-specific placement for green and grey infrastructure simultaneously. A multi-criterion decision-making framework for runoff control infrastructure spatial planning was therefore developed in this study. The pressure-state-response framework was applied to creatively match the pressure induced adjustment demands with the infrastructure effectiveness. The pressures were quantified from the perspective of environment, economy, and ecology on a grid scale. States were considered as the relative priority of regional pressure adjustment demand in multiple perspectives. Responses were presented as state-targeted green and grey infrastructure placement. Multi-perspective effectiveness of different green and grey infrastructure was simultaneously evaluated at an effective scale of controlling 1 m3/s runoff for comparison. Methods such as data mining, hydrological model simulation, and remote sensing inversion were combined to quantify the regional pressures. The capital investment and ecological impact of infrastructures were quantified from a life cycle perspective. A case study was carried out in Wuhan, China. The study area was clustered by gridded pressure into three regions. In region Ⅰ, ecological and environmental pressure were of higher weight. In region Ⅱ, the environmental pressure was dominant. In region Ⅲ, the ecological pressure took precedence over the environmental and economic constraints. The area ratios of the region Ⅰ, Ⅱ, and Ⅲ were 43%, 36%, and 21% respectively. The result indicated a synergy and spatial heterogeneity of multi-perspective pressures, and further demonstrating that expert experience tends to fail to weigh the multi-function of green and grey infrastructures for coping with the pressures. Results also stated that green infrastructures were more acceptable in areas that aspire to achieve simultaneous runoff control and ecological improvement. The decision-making framework developed in this study can maximize the overall performance by providing targeted infrastructure placement solutions.

Management impacts on the dissolved organic carbon release from deadwood, ground vegetation and the forest floor in a temperate Oak woodland.

The forest floor is often considered the most important source of dissolved organic carbon (DOC) in forest soils, yet little is known about the relative contribution from different forest floor layers, understorey vegetation and deadwood. Here, we determine the carbon stocks and potential DOC production from forest materials: deadwood, ground vegetation, leaf litter, the fermentation layer and top mineral soil (Ah horizon), and further assess the impact of management. Our research is based on long-term monitoring plots in a temperate deciduous woodland, with one set of plots actively managed by thinning, understorey scrub and deadwood removal, and another set that were not managed in 23 years. We examined long-term data and a spatial survey of forest materials to estimate the relative carbon stocks and concentrations and fluxes of DOC released from these different pools. Long-term soil water monitoring revealed a large difference in median DOC concentrations between the unmanaged (43.8 mg L-1) and managed (18.4 mg L-1) sets of plots at 10 cm depth over six years, with the median DOC concentration over twice as high in the unmanaged plots. In our spatial survey, a significantly larger cumulative flux of DOC was released from the unmanaged than the managed site, with 295.5 and 230.3 g m-2, respectively. Whilst deadwood and leaf litter released the greatest amount of DOC per unit mass, when volume of the material was considered, leaf litter contributed most to DOC flux, with deadwood contributing least. Likewise, there were significant differences in the carbon stocks held by different forest materials that were dependent on site. Vegetation and the fermentation layer held more carbon in the managed site than unmanaged, whilst the opposite occurred in deadwood and the Ah horizon. These findings indicate that management affects the allocation of carbon stored and DOC released between different forest materials.

Treatment outcomes of patients with Atopic Dermatitis (AD) treated with dupilumab through the Early Access to Medicines Scheme (EAMS) in the UK.

BACKGROUND: Dupilumab, a monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits IL-4/IL-13 signalling is indicated in dermatology for the treatment of moderate-to-severe atopic dermatitis (AD) in adult and adolescent patients 12 years and older and severe AD in children 6-11 years, who are candidates for systemic therapy. Dupilumab received Early Access to Medicines Scheme (EAMS) approval for adults in March 2017. OBJECTIVES: The purpose of this study was to assess the efficacy outcomes of treatment with dupilumab in EAMS. METHODS: A retrospective analysis of adult patients enrolled in the dupilumab EAMS in the UK. Scores were assessed at baseline and follow up, including the Eczema Area and Severity Index (EASI), Investigator's Global Assessment Score (IGA) and Dermatology Life Quality Index (DLQI). RESULTS: Data were available for 57 adult patients treated with dupilumab for at least 12 weeks; 73.6% of patients had received prior treatment with 3 or 4 immunosuppressants. Baseline scores for the EASI and DLQI were 27.93 (standard deviation, SD 13.09) and 18.26 (SD 6.18) respectively. AD severity scores showed statistically significant improvement at week 16±4 weeks (p <0.001 for all). The mean change in EASI was 14.13 points with 66.7% and 36.7% achieving a 50% (EASI-50) and 75% (EASI-75) improvement in EASI, respectively at 16+/- 4 weeks. IGA scores improved by at least two categories for 75% patients. DLQI scores decreased by a mean of 9.0 points, with 80% patients demonstrating a MCID 4-point improvement. For 85% patients, clinicians rated the treatment response as being either 'better' (19%) or 'much better' (65%). CONCLUSIONS: Dupilumab is associated with a significant and clinically relevant improvements in AD as measured by patient- and physician-reported outcome measures. Importantly, the clinical efficacy, despite the refractory disease of this EAMS cohort, is comparable to that previously reported in clinical trials.

Single-cell RNA sequencing profiling in a patient with discordant primary cutaneous B-cell and T-cell lymphoma reveals micromilieu-driven immune skewing.

BACKGROUND: Primary cutaneous lymphomas comprise a heterogeneous group of B-cell and T-cell malignancies which often show an indolent course, but can progress to aggressive disease in a subset of patients. Diagnosis is often delayed owing to clinical and histopathological similarities with benign inflammatory conditions. Especially during early disease, cancer cells are present at relatively low percentages compared with the inflammatory infiltrate, an interplay that is currently only insufficiently understood. OBJECTIVES: To improve diagnostics and perform molecular characterization of a complex type of primary cutaneous lymphoma. METHODS: Single-cell RNA sequencing (scRNA-seq) was performed and combined with T-cell and B-cell receptor sequencing. RESULTS: We were able to diagnose a patient with concurrent mycosis fungoides (MF) and primary cutaneous follicle centre lymphoma (PCFCL), appearing in mutually exclusive skin lesions. Profiling of tumour cells and the tissue microenvironment revealed a type-2 immune skewing in MF, most likely guided by the expanded clone that also harboured upregulation of numerous pro-oncogenic genes. By contrast, PCFCL lesions exhibited a more type-1 immune phenotype, consistent with its indolent behaviour. CONCLUSIONS: These data not only illustrate the diagnostic potential of scRNA-seq, but also allow the characterization of specific clonal populations that shape the unique tissue microenvironment in clinically distinct types of lymphoma skin lesions.

Educating health professionals to implement evidence-based falls screening in hospitals.

OBJECTIVE: International evidence-based guidelines advise traditional Falls Risk Assessment Tools (FRATs) should not be routinely used to predict the risk of a patient falling in hospital. However, disinvestment from existing services can be challenging. This study applied evidence-based approaches to education design to implement best practice guidelines. DESIGN: Mixed methods using questionnaires to evaluate health professionals' knowledge of evidence-based falls risk assessment and mitigation, followed by semi-structured interviews with individual health professionals. SETTING: Five Australian hospitals. PARTICIPANTS: There were two cohorts per hospital; Cohort 1 (C1) comprised 10 clinical leaders from nursing and allied health professions. Cohort 2 (C2) included clinicians involved in routine hospital falls screening and prevention. METHODS: 46 clinical leaders received a 3-h high quality education workshop on the latest evidence in hospital falls risk assessment and how to implement a new falls screening and management tool. They were also taught the practical skills to deliver a 1-h education session to C2 (n = 129). RESULTS: The education workshop significantly changed C1's views about evidence-based guidelines for falls screening and prevention. C1 were significantly more likely than C2 to feel confident in assessing falls risk and judging and implementing the best mitigation strategies. After the workshop, C1 were prepared and motivated to educate others on falls prevention and were satisfied with the skills gained. Six months after the workshop, C1 reported feeling more prepared for preventing falls. CONCLUSION: Health professionals benefitted from an interactive education workshop on how to use a new evidence-based hospital falls screening tool to help mitigate risk. An abridged version of the workshop did not result in long lasting effects. Education is an important element aiding disinvestment from non-evidence-based services, and implementation of clinical guidelines.

Postoperative pulmonary complications following major head and neck cancer surgery.

The primary aim of this observational study was to describe the incidence of postoperative pulmonary complications (PPCs) in 60 consecutive, surgically treated head and neck cancer patients requiring free flap reconstruction and tracheostomy, using both a prospective and a retrospective outcome measure. Secondary aims were to identify risk factors for PPC development, explore the effects of PPC on outcomes, and describe the provision of postoperative physiotherapy in this population. Postoperative pulmonary complications occurred in nine (15%) patients based on the Melbourne Group Scale and 27 (45%) patients based on Health Information Service coding data. The occurrence of a PPC was not statistically correlated with age, smoking history, comorbidities, operative time, or type of resection or free flap. Patients who developed a PPC, compared to those who did not, had a higher preoperative body mass index (P=0.022) and were more likely to be sat out of bed earlier post-surgery (P=0.038). Overall, patients required a median of 9.0 (interquartile range 7.0-11.0) physiotherapy sessions. Patients developing a PPC required significantly more physiotherapy sessions (P=0.007) and additional days of supplemental oxygen (P=0.022) as compared to those without a PPC, despite a similar hospital length of stay. In future, targeted physiotherapy interventions may reduce PPCs in this population.

Education interventions for health professionals on falls prevention in health care settings: a 10-year scoping review.

BACKGROUND: Falls in hospitals are a major risk to patient safety. Health professional education has the potential to be an important aspect of falls prevention interventions. This scoping review was designed to investigate the extent of falls prevention education interventions available for health professionals, and to determine the quality of reporting. METHOD: A five stage scoping review process was followed based on Arksey and O'Malley's framework and refined by the Joanna Briggs Institute Methodology for JBI Scoping Reviews. Five online databases identified papers published from January 2008 until May 2019. Papers were independently screened by two reviewers, and data extracted and analysed using a quality reporting framework. RESULTS: Thirty-nine publications were included. Interventions included formal methods of educational delivery (for example, didactic lectures, video presentations), interactive learning activities, experiential learning, supported learning such as coaching, and written learning material. Few studies employed comprehensive education design principles. None used a reporting framework to plan, evaluate, and document the outcomes of educational interventions. CONCLUSIONS: Although health professional education is recognised as important for falls prevention, no uniform education design principles have been utilised in research published to date, despite commonly reported program objectives. Standardised reporting of education programs has the potential to improve the quality of clinical practice and allow studies to be compared and evaluated for effectiveness across healthcare settings.

Efficient extraction of high pulse energy from partly quenched highly Er3+-doped fiber amplifiers.

We demonstrate efficient pulse-energy extraction from a partly quenched erbium-doped aluminosilicate fiber amplifier. This has a high erbium concentration that allows for short devices with reduced nonlinear distortions but also results in partial quenching and thus significant unsaturable absorption, even though the fiber is still able to amplify. Although the quenching degrades the average-power efficiency, the pulse energy remains high, and our results point to an increasingly promising outcome for short pulses. Furthermore, unlike unquenched fibers, the conversion efficiency improves at low repetition rates, which we attribute to smaller relative energy loss to quenched ions at higher pulse energy. A short (2.6 m) cladding-pumped partly quenched Er-doped fiber with 95-dB/m 1530-nm peak absorption and saturation energy estimated to 85 µJ reached 0.8 mJ of output energy when seeded by 0.2-µs, 23-µJ pulses. Thus, according to our results, pulses can be amplified to high energy in short highly Er-doped fibers designed to reduce nonlinear distortions at the expense of average-power efficiency.

CRISPR-Cas9-mediated labelling of the C-terminus of human laminin ß1 leads to secretion inhibition.

OBJECTIVES: The laminins (LM) are a family of basement membranes glycoproteins with essential roles in supporting epithelia, endothelia, nerves and muscle adhesion, and in regulating a range of processes including cell migration, stem cell maintenance and differentiation. However, surprisingly little is known about the mechanisms of turnover and remodelling of LM networks due to lack of appropriate tools to study these processes at the necessary resolution. Recently, the nematode C. elegans ortholog of human the LMß1 chain was labelled at the C-terminus with the photoconvertible fluorophore Dendra2. Here we used genome editing to establish a similar system in a mammalian cell line as proof of concept for future mammalian models. RESULTS: CRISPR-Cas9 was used to introduce the Dendra2 sequence at the C-terminus of LMß1 in the human lung adenocarcinoma cell line A549. Despite expression of the tagged protein within cells, no detectable LMß1-Dendra2 protein was deposited to the extracellular matrices or conditioned media of edited cells. Moreover, the edited cells displayed reduced proliferation rates. Together, these data suggest that, in humans, addition of C-terminal Dendra2 tag to LMß1 inhibits LM secretion, and is not a viable approach for use in animal models.

Educating health professionals to optimise falls screening in hospitals: protocol for a mixed methods study.

BACKGROUND: Falls in hospitals remain a major challenge to patient safety. All hospitalised adults are at risk of falling during their inpatient stay, though this risk is not always realised by patients and clinicians. This study will evaluate the outcomes of a hospital clinician education program that teaches clinicians how to screen for falls risk and assign mitigation strategies using clinical reasoning, rather than relying on a standardised falls risk assessment tool (FRAT). The education program aims to increase clinician knowledge, motivation and confidence in screening falls risk and selecting individual falls prevention interventions. Perceptions of the education intervention will also be examined. METHODS: Participants will be a sample of convenience of nurses and allied health professionals from five Australian hospitals. For each hospital there will be two cohorts. Cohort 1 will be clinical leaders who shall receive a three-hour education program on the latest evidence in hospital falls risk assessment and how to implement a new falls screening and management tool. They will also be taught practical skills to enable them to deliver an effective one-hour in-service training session to Cohort 2. Cohort 2 will be recruited from the workforce as a whole and include nurses and other health professionals involved in routine hospital falls screening and prevention. The investigation will be framed on Keller's Model of Motivational Design and Kirkpatrick's evaluation framework. It will involve a mixed methods pre and post-test questionnaire design inclusive of semi-structured telephone interviews, to triangulate the data from multiple approaches. DISCUSSION: This study will quantify the outcomes of a high-quality clinician education program to increase knowledge of evidence-based practice for falls prevention. It is predicted that positive behavioural changes will occur in health professionals, leading to organisational change and improved patient outcomes. Furthermore, the findings from the study will inform the future refinement of educational delivery to health professionals across hospital sites. TRIAL REGISTRATION: The study has also been approved by the Australian New Zealand Clinical Trials Registry: Preventing Hospital Falls: Optimal Screening UTN U1111-1225-8450. Universal Trial Number (UTN): U1111-1228-0041 (obtained 5/2/19). Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000200189 (obtained 12/2/19).

The influence of extensive green roofs on rainwater runoff quality: a field-scale study in southwest China.

Green roofs of young age (≤ 5 years old) have boomed in China since the Sponge City Construction initiative was implemented. To use green roofs for better urban stormwater management, it is necessary to investigate the runoff quality of field-scale young green roofs as well as to examine common plant-media combination in green roof projects of China. The influence of two Sedum-vegetated extensive green roofs of different designs at the early stage of operation on runoff water quality was investigated by a field-scale study in Chengdu, southwest China. The water quality parameters of pH, suspended solids (SS), chemical oxygen demand (COD), total phosphorus (TP), and total nitrogen (TN) of rainwater (that is, input water for roofs), runoff from the two green roofs, and runoff from a conventional concrete control roof were compared. The results indicate that both green roofs mainly act as pollutant sources with greater concentrations of SS, COD, and TP when compared with rainwater quality. When compared with runoff quality from the control roof, greater TP concentrations in runoff from one green roof with commercially available substrate were observed. Attention should be paid to TP leaching in runoff for retrofitted green roofs with imported commercial substrates in that region. Adoption of pre-cultivated S. lineare mats of low fertility and localized soils may reduce nutrient leaching in green roof runoff. A nitrogen-rich substrate is not recommended for a plant community of a single species. Investigation of the effect of green roofs on water quality involving various pollutants in the long run is recommended.

Optimal adaptation pathway for sustainable low impact development planning under deep uncertainty of climate change: A greedy strategy.

Robustness and cost effectiveness are major concerns for sustainable stormwater management under deep uncertainty of climate change. Given that many traditional static planning strategies are not working with unpredictable future conditions, the possibility of system failure, and the lock-in effects, the Adaptation Pathway (AP) approach was adopted for dynamically robust and cost-effective planning in this paper. In order to increase optimization accuracy of multi-staged planning, a continuous definition of the AP optimization problem was raised by improving the simplified versions in existing studies. A case study in Suzhou, a provincial pilot Sponge City in China undergoing increasing annual rainfall and severe water environment deterioration, was included by integrating Long-Term Hydrologic Impact Assessment-Low Impact Development model with optimization methods, aiming to persistently control the non-point source total phosphorus loading below an acceptable amount in the following unforeseen 20 years via multi-staged low-impact development (LID) construction. A novel optimization method developed by the authors in a companion paper, namely marginal-cost-based greedy strategy (MCGS), was successfully applied to efficiently solve the continuous version of the AP optimization problem. The popular genetic algorithm (GA) was used as a contrast. A weather generator was elaborated based on four Representative Concentration Pathway scenarios and 17 spatial downscaled general circulation models to simulate the unforeseen future annual rainfalls that helped with evaluating cost effectiveness of each prospective LID plan. Results showed that the adaptation pathways optimized by MCGS could save the whole life net present cost of an LID plan by 1%-60% compared with those optimized by GA, and the computational efficiency of MCGS was over 13 times faster than GA.

Systems based analysis of human embryos and gene networks involved in cell lineage allocation.

BACKGROUND: Little is understood of the molecular mechanisms involved in the earliest cell fate decision in human development, leading to the establishment of the trophectoderm (TE) and inner cell mass (ICM) stem cell population. Notably, there is a lack of understanding of how transcriptional networks arise during reorganisation of the embryonic genome post-fertilisation. RESULTS: We identified a hierarchical structure of preimplantation gene network modules around the time of embryonic genome activation (EGA). Using network models along with eukaryotic initiation factor (EIF) and epigenetic-associated gene expression we defined two sets of blastomeres that exhibited diverging tendencies towards ICM or TE. Analysis of the developmental networks demonstrated stage specific EIF expression and revealed that histone modifications may be an important epigenetic regulatory mechanism in preimplantation human embryos. Comparison to published RNAseq data confirmed that during EGA the individual 8-cell blastomeres are transcriptionally primed for the first lineage decision in development towards ICM or TE. CONCLUSIONS: Using multiple systems biology approaches to compare developmental stages in the early human embryo with single cell transcript data from blastomeres, we have shown that blastomeres considered to be totipotent are not transcriptionally equivalent. Furthermore we have linked the developmental interactome to individual blastomeres and to later cell lineage. This has clinical implications for understanding the impact of fertility treatments and developmental programming of long term health.