Housing Boston's Chronically Homeless Unsheltered Population: 14 Years Later.

OBJECTIVE: The long-term outcomes of permanent supportive housing for chronically unsheltered individuals, or rough sleepers, are largely unknown. We therefore assessed housing outcomes for a group of unsheltered individuals who were housed directly from the streets after living outside for decades. METHODS: Using an open-cohort design, 73 chronically unsheltered individuals were enrolled and housed in permanent supportive housing directly from the streets of Boston from 2005 to 2019. Through descriptive, regression, and survival analysis, we assessed housing retention, housing stability, and predictors of survival. RESULTS: Housing retention at ≥1 year was 82% yet fell to 36% at ≥5 years; corresponding Kaplan-Meier estimates for retention were 72% at ≥1, 42.5% at ≥5, and 37.5% at ≥10 years. Nearly half of the cohort (45%) died while housed. The co-occurrence of medical, psychiatric, and substance use disorder, or "trimorbidity," was common. Moves to a new apartment were also common; 38% were moved 45 times to avoid an eviction. Each subsequent housing relocation increased the risk of a tenant returning to homelessness. Three or more housing relocations substantially increased the risk of death. CONCLUSIONS: Long-term outcomes for this permanent supportive housing program for chronically unsheltered individuals showed low housing retention and poor survival. Housing stability for this vulnerable population likely requires more robust and flexible and long-term medical and social supports.

When did Homo sapiens first reach Southeast Asia and Sahul?

Anatomically modern humans (Homo sapiens, AMH) began spreading across Eurasia from Africa and adjacent Southwest Asia about 50,000-55,000 years ago (ca 50-55 ka). Some have argued that human genetic, fossil, and archaeological data indicate one or more prior dispersals, possibly as early as 120 ka. A recently reported age estimate of 65 ka for Madjedbebe, an archaeological site in northern Sahul (Pleistocene Australia-New Guinea), if correct, offers what might be the strongest support yet presented for a pre-55-ka African AMH exodus. We review evidence for AMH arrival on an arc spanning South China through Sahul and then evaluate data from Madjedbebe. We find that an age estimate of >50 ka for this site is unlikely to be valid. While AMH may have moved far beyond Africa well before 50-55 ka, data from the region of interest offered in support of this idea are not compelling.

Substance consumption and intoxication patterns in a medically supervised overdose prevention program for people experiencing homelessness.

Background: Opioid overdose is a leading cause of death among homeless individuals. Combining psychoactive substances with opioids increases overdose risk. This study aimed to describe intoxication patterns at a drop-in space offering medical monitoring and harm reduction services to individuals who arrive intoxicated and at risk of overdose. Methods: We examined data from visits to the Supportive Place for Observation and Treatment at Boston Health Care for the Homeless Program between January 1, 2017 and December 31, 2017. We used k-means cluster analysis to characterize intoxication patterns based on clinically assessed sedation levels and vital sign parameters. Multinomial logistic regression analysis assessed demographic and substance consumption predictors of cluster membership. Linear and logistic regression models examined associations between cluster membership and care outcomes. Results: Across 305 care episodes involving 156 unique patients, cluster analysis revealed 3 distinct intoxication patterns. Cluster A (26.6%) had mild sedation and normal vital signs. Cluster B (44.5%) featured greater sedation with bradycardia and/or hypotension. Cluster C (28.9%) was comparable to cluster B but with the addition of hypoxia. Self-reported consumption of non-opioid sedatives prior to arrival was common (63.3% of episodes) and predicted membership in cluster B (aOR 2.75, 95% CI 1.40, 5.40) and cluster C (aOR 3.38, 95% CI 1.48, 7.70). In comparison to cluster A episodes, cluster C episodes were longer (mean 4.8 vs. 2.3 hours, p < 0.001) and more likely to require supplemental oxygen (27.3% vs. 2.5%, p < 0.001). Few episodes required hospital transfer (4.7%) or naloxone (1.0%). No deaths occurred. Conclusions: In a medically supervised overdose monitoring program, reported use of non-opioid sedatives strongly predicted more complex clinical courses and should be factored into overdose prevention efforts. Low-threshold medical monitoring in an ambulatory setting was sufficient for most episodes, suggesting a role for such programs in reducing harm and averting costly emergency services.

Ultrasound Image Classification of Thyroid Nodules Using Machine Learning Techniques.

Background and Objectives: Thyroid nodules are lumps of solid or liquid-filled tumors that form inside the thyroid gland, which can be malignant or benign. Our aim was to test whether the described features of the Thyroid Imaging Reporting and Data System (TI-RADS) could improve radiologists' decision making when integrated into a computer system. In this study, we developed a computer-aided diagnosis system integrated into multiple-instance learning (MIL) that would focus on benign-malignant classification. Data were available from the Universidad Nacional de Colombia. Materials and Methods: There were 99 cases (33 Benign and 66 malignant). In this study, the median filter and image binarization were used for image pre-processing and segmentation. The grey level co-occurrence matrix (GLCM) was used to extract seven ultrasound image features. These data were divided into 87% training and 13% validation sets. We compared the support vector machine (SVM) and artificial neural network (ANN) classification algorithms based on their accuracy score, sensitivity, and specificity. The outcome measure was whether the thyroid nodule was benign or malignant. We also developed a graphic user interface (GUI) to display the image features that would help radiologists with decision making. Results: ANN and SVM achieved an accuracy of 75% and 96% respectively. SVM outperformed all the other models on all performance metrics, achieving higher accuracy, sensitivity, and specificity score. Conclusions: Our study suggests promising results from MIL in thyroid cancer detection. Further testing with external data is required before our classification model can be employed in practice.

SPIN2: Predicting sequence profiles from protein structures using deep neural networks.

Designing protein sequences that can fold into a given structure is a well-known inverse protein-folding problem. One important characteristic to attain for a protein design program is the ability to recover wild-type sequences given their native backbone structures. The highest average sequence identity accuracy achieved by current protein-design programs in this problem is around 30%, achieved by our previous system, SPIN. SPIN is a program that predicts sequences compatible with a provided structure using a neural network with fragment-based local and energy-based nonlocal profiles. Our new model, SPIN2, uses a deep neural network and additional structural features to improve on SPIN. SPIN2 achieves over 34% in sequence recovery in 10-fold cross-validation and independent tests, a 4% improvement over the previous version. The sequence profiles generated from SPIN2 are expected to be useful for improving existing fold recognition and protein design techniques. SPIN2 is available at http://sparks-lab.org.

Hunter-gatherer studies and human evolution: A very selective review.

The century long publication of this journal overlapped major changes in the sciences it covers. We have been eyewitnesses to vast changes during the final third of the last century and beginning of this one, momentous enough to fundamentally alter our work separately and collectively. One (NBJ) from animal ethology, another from western North American archaeology (JOC), and a third (KH) from cultural anthropology came to longtime collaboration as evolutionary ecologists with shared focus on studying modern hunter-gatherers to guide hypotheses about human evolution. Our findings have radically revised hypotheses each of us took for granted when we began. Our (provisional) conclusions are not the consensus among hunter-gatherer specialists; but grateful that personal reflections are invited, we aim to explain how and why we continue to bet on them.

Prevalence and Genetic Diversity of Grabloviruses in Free-Living Vitis spp.

The distribution and diversity of grapevine red blotch virus (GRBV) and wild Vitis virus 1 (WVV1) (genus Grablovirus; family Geminiviridae) were determined in free-living Vitis spp. in northern California and New York from 2013 to 2017. Grabloviruses were detected by polymerase chain reaction in 28% (57 of 203) of samples from California but in none of the 163 samples from New York. The incidence of GRBV in free-living vines was significantly higher in samples from California counties with high compared with low grape production (χ2 = 83.09; P < 0.001), and in samples near (<5 km) to compared with far (>5 km) from vineyards (χ2 = 57.58; P < 0.001). These results suggested a directional spread of GRBV inoculum predominantly from vineyards to free-living Vitis spp. WVV1 incidence was also significantly higher in areas with higher grape production acreage (χ2 = 16.02; P < 0.001). However, in contrast to GRBV, no differential distribution of WVV1 incidence was observed with regard to distance from vineyards (χ2 = 0.88; P = 0.3513). Two distinct phylogenetic clades were identified for both GRBV and WVV1 isolates from free-living Vitis spp., although the nucleotide sequence variability of the genomic diversity fragment was higher for WWV1 (94.3 to 99.8% sequence identity within clade 1 isolates and 90.1 to 100% within clade 2 isolates) than GRBV (98.3% between clade 1 isolates and 96.9 to 100% within clade 2 isolates). Additionally, evidence for intraspecific recombination events was found in WVV1 isolates and confirmed in GRBV isolates. The prevalence of grabloviruses in California free-living vines highlights the need for vigilance regarding potential grablovirus inoculum sources in order to protect new vineyard plantings and foundation stock vineyards in California.

The pyrophilic primate hypothesis.

Members of genus Homo are the only animals known to create and control fire. The adaptive significance of this unique behavior is broadly recognized, but the steps by which our ancestors evolved pyrotechnic abilities remain unknown. Many hypotheses attempting to answer this question attribute hominin fire to serendipitous, even accidental, discovery. Using recent paleoenvironmental reconstructions, we present an alternative scenario in which, 2 to 3 million years ago in tropical Africa, human fire dependence was the result of adapting to progressively fire-prone environments. The extreme and rapid fluctuations between closed canopy forests, woodland, and grasslands that occurred in tropical Africa during that time, in conjunction with reductions in atmospheric carbon dioxide levels, changed the fire regime of the region, increasing the occurrence of natural fires. We use models from optimal foraging theory to hypothesize benefits that this fire-altered landscape provided to ancestral hominins and link these benefits to steps that transformed our ancestors into a genus of active pyrophiles whose dependence on fire for survival contributed to its rapid expansion out of Africa.

Tobacco-, alcohol-, and drug-attributable deaths and their contribution to mortality disparities in a cohort of homeless adults in Boston.

OBJECTIVES: We quantified tobacco-, alcohol-, and drug-attributable deaths and their contribution to mortality disparities among homeless adults. METHODS: We ascertained causes of death among 28 033 adults seen at the Boston Health Care for the Homeless Program in 2003 to 2008. We calculated population-attributable fractions to estimate the proportion of deaths attributable to tobacco, alcohol, or drug use. We compared attributable mortality rates with those for Massachusetts adults using rate ratios and differences. RESULTS: Of 1302 deaths, 236 were tobacco-attributable, 215 were alcohol-attributable, and 286 were drug-attributable. Fifty-two percent of deaths were attributable to any of these substances. In comparison with Massachusetts adults, tobacco-attributable mortality rates were 3 to 5 times higher, alcohol-attributable mortality rates were 6 to 10 times higher, and drug-attributable mortality rates were 8 to 17 times higher. Disparities in substance-attributable deaths accounted for 57% of the all-cause mortality gap between the homeless cohort and Massachusetts adults. CONCLUSIONS: In this clinic-based cohort of homeless adults, over half of all deaths were substance-attributable, but this did not fully explain the mortality disparity with the general population. Interventions should address both addiction and non-addiction sources of excess mortality.

An Inpatient Protocol for the Treatment of Methamphetamine Withdrawal in Patients With and Without Opioid Use Disorder.

OBJECTIVE: Increasing rates of methamphetamine (METH) use, use disorders, and related overdoses are a growing public health problem. There are a lack of protocols addressing METH intoxication and withdrawal symptoms that manifest during acute withdrawal treatment resulting in inpatient management difficulties and premature discharges. This report presents a novel treatment protocol comprised of behavior-targeted and pharmacological components that aims to reduce the intensity and duration of METH intoxication and withdrawal related symptoms during early treatment, improve retention, and provide clinicians with a tool to meet this growing problem. METHODS: The protocol was developed by a team of addiction physicians and other clinical staff. Clinical and administrative staff at a community acute stabilization unit were trained and the protocol was implemented with patients presenting with METH use. Pharmacological interventions, including ascorbic acid, antipsychotics, and other sedatives are discussed, as are behavior-based orders. A retrospective quality assurance examination was conducted on patient characteristics and outcomes as well as focus groups with nursing staff. RESULTS: A total of 23 patients consecutively admitted to the unit used the protocol (100% male). Most patients (67%) displayed symptoms of METH use or withdrawal. Behavior-related interventions were used in 52% of patients, while 48% received behavior-related and pharmacological measures. Patient completion of the protocol was 83%, and the protocol's utility was supported by nursing staff. CONCLUSIONS: This retrospective evaluation of a novel METH withdrawal treatment protocol suggests feasibility, tolerability, and preliminary evidence of effectiveness, providing clinicians with a new tool that requires further study.

mTOR direct interactions with Rheb-GTPase and raptor: sub-cellular localization using fluorescence lifetime imaging.

BACKGROUND: The mammalian target of rapamycin (mTOR) signalling pathway has a key role in cellular regulation and several diseases. While it is thought that Rheb GTPase regulates mTOR, acting immediately upstream, while raptor is immediately downstream of mTOR, direct interactions have yet to be verified in living cells, furthermore the localisation of Rheb has been reported to have only a cytoplasmic cellular localization. RESULTS: In this study a cytoplasmic as well as a significant sub-cellular nuclear mTOR localization was shown , utilizing green and red fluorescent protein (GFP and DsRed) fusion and highly sensitive single photon counting fluorescence lifetime imaging microscopy (FLIM) of live cells. The interaction of the mTORC1 components Rheb, mTOR and raptor, tagged with EGFP/DsRed was determined using fluorescence energy transfer-FLIM. The excited-state lifetime of EGFP-mTOR of ~2400 ps was reduced by energy transfer to ~2200 ps in the cytoplasm and to 2000 ps in the nucleus when co-expressed with DsRed-Rheb, similar results being obtained for co-expressed EGFP-mTOR and DsRed-raptor. The localization and distribution of mTOR was modified by amino acid withdrawal and re-addition but not by rapamycin. CONCLUSIONS: The results illustrate the power of GFP-technology combined with FRET-FLIM imaging in the study of the interaction of signalling components in living cells, here providing evidence for a direct physical interaction between mTOR and Rheb and between mTOR and raptor in living cells for the first time.

Comparing homeless persons' care experiences in tailored versus nontailored primary care programs.

OBJECTIVES: We compared homeless patients' experiences of care in health care organizations that differed in their degree of primary care design service tailoring. METHODS: We surveyed homeless-experienced patients (either recently or currently homeless) at 3 Veterans Affairs (VA) mainstream primary care settings in Pennsylvania and Alabama, a homeless-tailored VA clinic in California, and a highly tailored non-VA Health Care for the Homeless Program in Massachusetts (January 2011-March 2012). We developed a survey, the "Primary Care Quality-Homeless Survey," to reflect the concerns and aspirations of homeless patients. RESULTS: Mean scores at the tailored non-VA site were superior to those from the 3 mainstream VA sites (P < .001). Adjusting for patient characteristics, these differences remained significant for subscales assessing the patient-clinician relationship (P < .001) and perceptions of cooperation among providers (P = .004). There were 1.5- to 3-fold increased odds of an unfavorable experience in the domains of the patient-clinician relationship, cooperation, and access or coordination for the mainstream VA sites compared with the tailored non-VA site; the tailored VA site attained intermediate results. CONCLUSIONS: Tailored primary care service design was associated with a superior service experience for patients who experienced homelessness.