Early mobilization in the critical care unit: A review of adult and pediatric literature.

Early mobilization of critically ill patients is beneficial, suggesting that it should be incorporated into daily clinical practice. Early passive, active, and combined progressive mobilizations can be safely initiated in intensive care units (ICUs). Adult patients receiving early mobilization have fewer ventilator-dependent days, shorter ICU and hospital stays, and better functional outcomes. Pediatric ICU data are limited, but recent studies also suggest that early mobilization is achievable without increasing patient risk. In this review, we provide a current and comprehensive appraisal of ICU mobilization techniques in both adult and pediatric critically ill patients. Contraindications and perceived barriers to early mobilization, including cost and health care provider views, are identified. Methods of overcoming barriers to early mobilization and enhancing sustainability of mobilization programs are discussed. Optimization of patient outcomes will require further studies on mobilization timing and intensity, particularly within specific ICU populations

EDEN Survey: Small Transiting Planet Detection Limits and Constraints on the Occurrence Rates for Late M Dwarfs within 15 pc

Earth-sized exoplanets that transit nearby, late spectral type red dwarfs will be prime targets for atmospheric characterization in the coming decade. Such systems, however, are difficult to find via wide-field transit surveys like Kepler or TESS. Consequently, the presence of such transiting planets is unexplored and the occurrence rates of short-period Earth-sized planets around late M dwarfs remain poorly constrained. Here, we present the deepest photometric monitoring campaign of 22 nearby late M dwarf stars, using data from over 500 nights on seven 1-2 meter class telescopes. Our survey includes all known single quiescent northern late M dwarfs within 15 pc. We use transit-injection-and-recovery tests to quantify the completeness of our survey, successfully identify most ($>80\%$) transiting short-period (0.5-1 d) super-Earths ($R > 1.9 R_\oplus$), and are sensitive ($\sim50\%$) to transiting Earth-sized planets ($1.0-1.2 R_\oplus$). Our high sensitivity to transits with a near-zero false positive rate demonstrates an efficient survey strategy. Our survey does not yield a transiting planet detection, yet it provides the most sensitive upper limits on transiting planets orbiting our target stars. Finally, we explore multiple hypotheses about the occurrence rates of short-period planets (from Earth-sized planets to giant planets) around late M dwarfs. We show, for example, that giant planets at short periods ($<1$ day) are uncommon around our target stars. Our dataset provides some insight into occurrence rates of short-period planets around TRAPPIST-1-like stars, and our results can help test planetary formation and system evolution models, as well as guide future observations of nearby late M dwarfs.Comment: 27 pages, 11 figure

Utilizing a Global Network of Telescopes to Update the Ephemeris for the Highly Eccentric Planet HD 80606 b and to Ensure the Efficient Scheduling of JWST

The transiting planet HD 80606 b undergoes a 1000 fold increase in insolation during its 111 days orbit due to it being highly eccentric (e = 0.93). The planet's effective temperature increases from 400 to over 1400 K in a few hours as it makes a rapid passage to within 0.03 au of its host star during periapsis. Spectroscopic observations during the eclipse (which is conveniently oriented a few hours before periapsis) of HD 80606 b with the James Webb Space Telescope (JWST) are poised to exploit this highly variable environment to study a wide variety of atmospheric properties, including composition, chemical and dynamical timescales, and large scale atmospheric motions. Critical to planning and interpreting these observations is an accurate knowledge of the planet's orbit. We report on observations of two full-transit events: 2020 February 7 as observed by the TESS spacecraft and 2021 December 7-8 as observed with a worldwide network of small telescopes. We also report new radial velocity observations which, when analyzed with a coupled model to the transits, greatly improves the planet's orbital ephemeris. Our new orbit solution reduces the uncertainty in the transit and eclipse timing of the JWST era from tens of minutes to a few minutes. When combined with the planned JWST observations, this new precision may be adequate to look for non-Keplerian effects in the orbit of HD 80606 b

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

Objective The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations

Population-Based Biochemistry, Immunologic and Hematological Reference Values for Adolescents and Young Adults in a Rural Population in Western Kenya

BACKGROUND: There is need for locally-derived age-specific clinical laboratory reference ranges of healthy Africans in sub-Saharan Africa. Reference values from North American and European populations are being used for African subjects despite previous studies showing significant differences. Our aim was to establish clinical laboratory reference values for African adolescents and young adults that can be used in clinical trials and for patient management. METHODS AND FINDINGS: A panel of 298, HIV-seronegative individuals aged 13-34 years was randomly selected from participants in two population-based cross-sectional surveys assessing HIV prevalence and other sexually transmitted infections in western Kenya. The adolescent (/=18 years) ratio and the male-to-female ratio was 1ratio1. Median and 95% reference ranges were calculated for immunohematological and biochemistry values. Compared with U.S-derived reference ranges, we detected lower hemoglobin (HB), hematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), neutrophil, glucose, and blood urea nitrogen values but elevated eosinophil and total bilirubin values. Significant gender variation was observed in hematological parameters in addition to T-bilirubin and creatinine indices in all age groups, AST in the younger and neutrophil, platelet and CD4 indices among the older age group. Age variation was also observed, mainly in hematological parameters among males. Applying U.S. NIH Division of AIDS (DAIDS) toxicity grading to our results, 40% of otherwise healthy study participants were classified as having an abnormal laboratory parameter (grade 1-4) which would exclude them from participating in clinical trials. CONCLUSION: Hematological and biochemistry reference values from African population differ from those derived from a North American population, showing the need to develop region-specific reference values. Our data also show variations in hematological indices between adolescent and adult males which should be considered when developing reference ranges. This study provides the first locally-derived clinical laboratory reference ranges for adolescents and young adults in western Kenya

Initial Visible and Mid-IR Characterization of P/2019 LD₂ (ATLAS), an Active Transitioning Centaur Among the Trojans, with Hubble, Spitzer, ZTF, Keck, APO and GROWTH Imaging and Spectroscopy

We present visible and mid-infrared imagery and photometry of Jovian co-orbital comet P/2019 LD₂ (ATLAS) taken with Hubble Space Telescope/WFC3 on 2020 April 1, Spitzer Space Telescope/IRAC on 2020 January 25, Zwicky Transient Facility between 2019 April 9 and 2019 Nov 8 and the GROWTH telescope network from 2020 May to July, as well as visible spectroscopy from Keck/LRIS on 2020 August 19. Our observations indicate that LD₂ has a nucleus with radius 0.2-1.8 km assuming a 0.08 albedo and that the coma is dominated by ∼100 μ m-scale dust ejected at ∼1 m/s speeds with a ∼1" jet pointing in the SW direction. LD₂ experienced a total dust mass loss of ∼10⁸ kg and dust mass loss rate of ∼6 kg/s with Afρ/cross-section varying between ∼85 cm/125 km² and ∼200 cm/310 km² between 2019 April 9 and 2019 Nov 8. If the Afρ/cross-section increase remained constant, it implies that LD₂ has remained active since ∼2018 November when it came within 4.8 au of the Sun, a typical distance for comets to begin sublimation of H₂O. From our 4.5 μm Spitzer observations, we set a limit on CO/CO₂ gas production of ∼10²⁷/∼10²⁶ mol/s. Multiple bandpass photometry of LD₂ taken by the GROWTH network measured in a 10,000 km aperture provide color measurements of g-r = 0.59±0.03, r-i = 0.18±0.05, and i-z = 0.01±0.07, colors typical of comets. We set a spectroscopic upper limit to the production of H₂O gas of ∼80 kg/s. Improving the orbital solution for LD₂ with our observations, we determine that the long-term orbit of LD₂ is that of a typical Jupiter Family Comet having close encounters with Jupiter coming within ∼0.5 Hill radius in the last ∼3 y to within 0.8 Hill radius in ∼9 y and has a 95% chance of being ejected from the Solar System in < 10 Myr

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients