PROPERTY Regulation of Specialized Land Transactions: Revise Georgia Land Sales Act; Remove Georgia Real Estate Commission as Administrator

The Act removes the Georgia Real Estate Commission (Commission) as administrator of the Georgia Land Sales Act (GLSA) and repeals the provision relating to fees and expenses, enforcement and sanctioning authority, and immunity of the Commission. The Act vests enforcement of the GLSA in the Attorney General or the district attorney. The Act repeals certain registration requirements of the GLSA, provides for mandatory use of the property reports in sales of subdivided land, and requires subdividers to keep business records. Furthermore, the Act changes the provisions of the GLSA pertaining to hearings and judicial review, cease and desist orders, and consent to service as it relates to actions by the Commission

INSURANCE Insurance Generally: Authorize Use of Preexisting Conditions Exclusions or Limitations in Group Policies or Contracts of Disability Income Insurance

The Act permits the use of preexisting conditions exclusions in group disability income insurance policies. Specifically, the Act provides a definition of preexisting condition and prohibits the use in group disability income insurance policies of any definition that is more restrictive than the statutory standard. The Act requires policies that exclude benefits for preexisting conditions to disclose such exclusions. Finally, the Act mandates that benefits will not be denied based on a preexisting condition if the resulting disability occurs more than two years after the commencement of coverage

Validation of the Global Distribution of CO\u3csub\u3e2\u3c/sub\u3e Volume Mixing Ratio in the Mesosphere and Lower Thermosphere from SABER

The Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on board the Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite has been measuring the limb radiance in 10 broadband infrared channels over the altitude range from ~ 400 km to the Earth\u27s surface since 2002. The kinetic temperatures and CO2 volume mixing ratios (VMRs) in the mesosphere and lower thermosphere have been simultaneously retrieved using SABER limb radiances at 15 and 4.3 μm under nonlocal thermodynamic equilibrium (non-LTE) conditions. This paper presents results of a validation study of the SABER CO2 VMRs obtained with a two-channel, self-consistent temperature/CO2 retrieval algorithm. Results are based on comparisons with coincident CO2 measurements made by the Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS) and simulations using the Specified Dynamics version of the Whole Atmosphere Community Climate Model (SD-WACCM). The SABER CO2 VMRs are in agreement with ACE-FTS observations within reported systematic uncertainties from 65 to 110 km. The annual average SABER CO2 VMR falls off from a well-mixed value above ~80 km. Latitudinal and seasonal variations of CO2 VMRs are substantial. SABER observations and the SD-WACCM simulations are in overall agreement for CO2 seasonal variations, as well as global distributions in the mesosphere and lower thermosphere. Not surprisingly, the CO2 seasonal variation is shown to be driven by the general circulation, converging in the summer polar mesopause region and diverging in the winter polar mesopause region. Key Points Mean SABER CO2 distribution is validated against SD-WACCM and ACE-FTS data SABER and ACE-FTS mean CO2 VMR agree within 5% below 90 km up to 20% at 110 km SD-WACCM and SABER CO2 spatial and seasonal distribution show a good agreement. © 2015. American Geophysical Union

Antidepressant prescribing practices for the treatment of children and adolescents.

OBJECTIVE: This study evaluates pediatric antidepressant prescribing practices of Nebraska clinicians. METHODS: Surveys were sent in July, 2005, to 1,521 prescribing clinicians throughout Nebraska to assess pediatric antidepressant use along with any practice changes following the U.S. Food and Drug Administration (FDA) black box warning issued in October, 2004. RESULTS: Over half (n = 866) of the clinicians responded to the survey, of which 96.8% reported awareness of the FDA black box warning. Of the respondents, 76.9% (n = 666) were prescribing antidepressants to children and/or adolescents. Clinicians reported decreased prescribing frequency for both children (15.5%) and adolescents (36.6%), with 36% having increased referrals to specialists. While 31.9% reported seeing patients more frequently upon initiation of antidepressants, only 7.5% reported weekly visits for the first month of treatment, as recommended by the FDA. Over one fifth (21.9%) reported a caregiver or patient had refused antidepressant medication treatment due to the FDA\u27s warning. CONCLUSION: Clinicians in Nebraska report changes in clinical practice due to the issuance of the FDA black box warning, with a decrease in prescribing antidepressants to pediatric patients and an increase in referrals to specialists. Although awareness of the FDA\u27s warning was evident among clinicians and patients, adherence to recommended guidelines was low

Demonstrating sub-3 ps temporal resolution in a superconducting nanowire single-photon detector

Improving the temporal resolution of single photon detectors has an impact on many applications, such as increased data rates and transmission distances for both classical and quantum optical communication systems, higher spatial resolution in laser ranging and observation of shorter-lived fluorophores in biomedical imaging. In recent years, superconducting nanowire single-photon detectors (SNSPDs) have emerged as the highest efficiency time-resolving single-photon counting detectors available in the near infrared. As the detection mechanism in SNSPDs occurs on picosecond time scales, SNSPDs have been demonstrated with exquisite temporal resolution below 15 ps. We reduce this value to 2.7$\pm$0.2 ps at 400 nm and 4.6$\pm$0.2 ps at 1550 nm, using a specialized niobium nitride (NbN) SNSPD. The observed photon-energy dependence of the temporal resolution and detection latency suggests that intrinsic effects make a significant contribution.Comment: 25 pages, 9 figure

SON-1210 - a novel bifunctional IL-12 / IL-15 fusion protein that improves cytokine half-life, targets tumors, and enhances therapeutic efficacy

BackgroundThe potential synergy between interleukin-12 (IL-12) and IL-15 holds promise for more effective solid tumor immunotherapy. Nevertheless, previous clinical trials involving therapeutic cytokines have encountered obstacles such as short pharmacokinetics, limited tumor microenvironment (TME) targeting, and substantial systemic toxicity.MethodsTo address these challenges, we fused single-chain human IL-12 and native human IL-15 in cis onto a fully human albumin binding (FHAB) domain single-chain antibody fragment (scFv). This novel fusion protein, IL12-FHAB-IL15 (SON-1210), is anticipated to amplify the therapeutic impact of interleukins and combination immunotherapies in human TME. The molecule was studied in vitro and in animal models to assess its pharmacokinetics, potency, functional characteristics, safety, immune response, and efficacy.ResultsSON-1210 demonstrated robust binding affinity to albumin and exhibited the anticipated in vitro activity and tumor model efficacy that might be expected based on decades of research on native IL-12 and IL-15. Notably, in the B16F10 melanoma model (a non-immunogenic, relatively “cold” tumor), the murine counterpart of the construct, which had mouse (m) and human (h) cytokine sequences for the respective payloads (mIL12-FHAB-hIL15), outperformed equimolar doses of the co-administered native cytokines in a dose-dependent manner. A single dose caused a marked reduction in tumor growth that was concomitant with increased IFNγ levels; increased Th1, CTL, and activated NK cells; a shift in macrophages from the M2 to M1 phenotype; and a reduction in Treg cells. In addition, a repeat-dose non-human primate (NHP) toxicology study displayed excellent tolerability up to 62.5 µg/kg of SON-1210 administered three times, which was accompanied by the anticipated increases in IFNγ levels. Toxicokinetic analyses showed sustained serum levels of SON-1210, using a sandwich ELISA with anti-IL-15 for capture and biotinylated anti-IL-12 for detection, along with sustained IFNγ levels, indicating prolonged kinetics and biological activity.ConclusionCollectively, these findings support the suitability of SON-1210 for patient trials in terms of activity, efficacy, and safety, offering a promising opportunity for solid tumor immunotherapy. Linking cytokine payloads to a fully human albumin binding domain provides an indirect opportunity to target the TME using potent cytokines in cis that can redirect the immune response and control tumor growth

A comparison of multiple Rosetta data sets and 3D model calculations of 67P/Churyumov-Gerasimenko coma around equinox (May 2015)

We have used the latest available shape model for gas and dust simulations of the inner coma of comet 67P/Churyumov-Gerasimenko for the period around May 2015 (equinox). We compare results from a purely insolation-driven model with a complementary set of observations made by ROSINA, VIRTIS, MIRO, and OSIRIS within the same period. The observations include - for the first time - inverted MIRO measurements of gas density, temperature and bulk velocity to constrain the model. The comparisons show that, as in November 2014 (Marschall et al., 2016), insolation-driven activity does not provide an adequate fit to the data. Both VIRTIS and MIRO observations indicate that emissions from the Hatmehit and Imhotep regions of the nucleus are strongly depleted in total gas, H2O, and dust emissions in this case. The MIRO inversion provides a challenging constraint to the models as a consequence of the terminator orbit and nucleus pointing of the spacecraft. Nonetheless a consistent picture with a dominance of outgassing from the Hapi region, even at equinox, is clearly evident. An inhomogeneous model consistent with models proposed for the November 2014 time-frame was constructed and provides a better fit to the data. As far as we are aware this is the first time comae data from four Rosetta instruments have been used to constrain within one self-contained model the emission distribution at the nucleus surface and study the dynamics of the gas and dust outflow

Molecular Characterization of Streptococcus Pneumoniae Causing Disease Among Children in Nigeria During the Introduction of PCV10 (GSK)

Streptococcus pneumoniae (pneumococcus) is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated ~49 000 child deaths caused by pneumococcal infections each year. Ten-valent pneumococcal conjugate vaccine (GSK; PCV10) was introduced in December 2014 in a phased approach. However, few studies have characterized the disease-causing pneumococci from Nigeria. This study assessed the prevalence of serotypes, antibiotic susceptibility and genomic lineages using whole genome sequencing and identified lineages that could potentially escape PCV10 (GSK). We also investigated the potential differences in pneumococcal lineage features between children with and without sickle cell disease. A collection of 192 disease-causing pneumococcal isolates was obtained from Kano (n=189) and Abuja (n=3) states, Nigeria, between 1 January 2014 and 31 May 2018. The majority (99 %, 190/192) of specimens were recovered from children aged 5 years or under. Among them, 37 children had confirmed or traits of sickle cell disease. Our findings identified 25 serotypes expressed by 43 Global Pneumococcal Sequence Clusters (GPSCs) and 85 sequence types (STs). The most common serotypes were 14 (18 %, n=35), 6B (16 %, n=31), 1 (9 %, n=17), 5 (9 %, n=17) and 6A (9 %, n=17); all except serotype 6A are included in PCV10 (GSK). PCV10 (SII; PNEUMOSIL) and PCV13 formulations include serotypes 6A and 19A which would increase the overall coverage from 67 % by PCV10 (GSK) to 78 and 82 %, respectively. The pneumococcal lineages were a mix of globally spreading and unique local lineages. Following the use of PCV10 (GSK), GPSC5 expressing serotype 6A, GPSC10 (19A), GPSC26 (12F and 46) and GPSC627 (9L) are non-vaccine type lineages that could persist and potentially expand under vaccine-selective pressure. Approximately half (52 %, 99/192) of the pneumococcal isolates were resistant to the first-line antibiotic penicillin and 44 % (85/192) were multidrug-resistant. Erythromycin resistance was very low (2 %, 3/192). There was no significant difference in clinical manifestation, serotype prevalence or antibiotic resistance between children with and without traits of or confirmed sickle cell disease. In summary, our findings show that a high percentage of the pneumococcal disease were caused by the serotypes that are covered by currently available vaccines. Given the low prevalence of resistance, macrolide antibiotics, such as erythromycin, should be considered as an option to treat pneumococcal disease in Nigeria. However, appropriate use of macrolide antibiotics should be vigilantly monitored to prevent the potential increase in macrolide resistance

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio