The Radio Ammonia Mid-plane Survey (RAMPS) Pilot Survey

The Radio Ammonia Mid-Plane Survey (RAMPS) is a molecular line survey that aims to map a portion of the Galactic midplane in the first quadrant of the Galaxy (l = 10°–40°, | b| \leqslant 0\buildrel{\circ}\over{.} 4) using the Green Bank Telescope. We present results from the pilot survey, which has mapped approximately 6.5 square degrees in fields centered at l = 10°, 23°, 24°, 28°, 29°, 30°, 31°, 38°, 45°, and 47°. RAMPS observes the NH3 inversion transitions NH3(1,1)–(5,5), the H2O 61,6–52,3 maser line at 22.235 GHz, and several other molecular lines. We present a representative portion of the data from the pilot survey, including NH3(1,1) and NH3(2,2) integrated intensity maps, H2O maser positions, maps of NH3 velocity, NH3 line width, total NH3 column density, and NH3 rotational temperature. These data and the data cubes from which they were produced are publicly available on the RAMPS website (http://sites.bu.edu/ramps/)

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial

Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. National Institute of Neurological Disorders and Stroke and Genentech. [Abstract copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Locoregional Prostate Cancer Treatment Pattern Variation in Independent Cancer Centers: Policy Effect, Patient Preference, or Physician Incentive?

Surveillance, Epidemiologic, and End Results (SEER) registry data abstracted from a priority 2 or higher reporting source from 2006 to 2008 were used to compare treatment patterns in 45–64-year old men diagnosed with locoregional prostate cancer (LRPC) across states with or without radiation therapy-directed certificate of need (CON) laws and across independent cancer centers (ICCs) compared to large multi-specialty groups (LMSGs). Adjusted treatment percentages for the five most common LRPC treatments (surgery, external beam radiation therapy (EBRT), combination brachytherapy with EBRT, brachytherapy, and observation) were compared using cross-sectional logistic regression between CON-unregulated and -regulated states and between LMSGs and ICCs. LRPC EBRT rates were no different across CON regions, but are increased in ICCs compared to LMSGs (37.00% vs. 13.23%, P < 0.001). Variation in LRPC treatment patterns by reporting source merits further scrutiny under the Affordable Care Act of 2010, considering the intent of incentivized accountable care organizations (ACOs) established by the Patient Protection and Affordable Care Act of 2010 (PPACA) and the implications of early descriptions of these new healthcare provider organizations on prostate cancer treatment patterns

Neurocognitive function outcomes in NRG/RTOG 0534, the SPPORT trial

12022 Background: RTOG 0534 established the benefit of adding of short term androgen deprivation therapy (PBRT+STADT, Arm 2) to prostate bed salvage radiotherapy (PBRT, Arm 1), and demonstrated that elective pelvic lymph node irradiation combined with STADT (PBRT+STADT+PLNRT, Arm 3) results in further reductions in progression. Longitudinal monitoring of neurocognitive function (NCF) was conducted to evaluate the hypothesis that patients treated with STADT will demonstrate greater decline in NCF compared to patients receiving PBRT alone. Methods: Patients were administered the Clinical Trial Battery [Hopkins Verbal Learning Test – Revised (HVLT-R), Trail Making Test (TMT), and the Controlled Oral Word Association (COWA) test] by certified test administrators at baseline, and at 6 weeks (6w), 1 year (1yr), and 5 years after the end of RT (5yr). Raw NCF tests scores were converted to standardized z-scores adjusted for age and education when necessary. Analyses included z-score change and reliable change index (RCI) determined decline compared to baseline, and longitudinal mixed effect regression models using z-scores. To control for multiplicity, p < 0.025 is required for statistical significance. Results: Among the 1716 analyzable patients, 429 consented to NCF monitoring. There were no significant differences in sociodemographic or clinical characteristics between arms. NCF test completion was 82, 76, 63 and 30% at baseline, 6w, 1yr, and 5yr, respectively. RCI-based NCF deterioration was more frequent in Arm 3 compared to Arm 1 at 6 weeks on Delayed Recall (16% vs. 7%, p = 0.023). Patients in Arm 3 evidenced greater z-score decline compared to patients in Arm 1 at 6w on HVLT-R Total Recall [M(SD) Z-score∆ = -0.1(1.0) vs 0.2(0.9), (p = 0.020)] and Delayed Recall [M(SD) Z-score∆ = -0.4(1.5) vs 0.1(1.2), (p = 0.012)]. Mixed effects models identified statistically significant differences in z-scores between Arm 3 and 1 at 6w on Delayed Recall [-0.541 (SE 0.178, p = 0.002)]. A statistically significant difference was observed between Arm 2 and 1 at 6w on TMTB [1.498 (SE 0.626, p = 0.017) favoring Arm 2]. Between arm differences were not seen at any other time point, or on other NCF outcomes. Conclusions: Compared to patients treated with PBRT alone, patients treated with PBRT+STADT+PLNRT exhibited greater worsening in episodic verbal learning and memory processes at 6 weeks after the end of RT, while patients treated with PBRT+STADT exhibited greater improvement in processing speed. The absence of long term or progressive cognitive decline associated with STADT-containing regimens is promising but limited by substantial missing data at year 5. FUNDING This project was supported by grants 10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), CTEP from the National Cancer Institute (NCI). Clinical trial information: NCT00567580

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial

Background: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. Methods: MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. Findings: Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). Interpretation: For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons