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Sub-acute ruminal acidosis (SARA) can reduce the production efficiency and impair the welfare of cattle, potentially in all production systems. The aim of this study was to characterise measurable postmortem observations from divergently managed intensive beef finishing farms with high rates of concentrate feeding. At the time of slaughter, we obtained samples from 19 to 20 animals on each of 6 beef finishing units (119 animals in total) with diverse feeding practices, which had been subjectively classified as being high risk (three farms) or low risk (three farms) for SARA on the basis of the proportions of barley, silage and straw in the ration. We measured the concentrations of histamine, lipopolysaccharide (LPS), lactate and other short-chain fatty acids (SCFAs) in ruminal fluid, LPS and SCFA in caecal fluid. We also took samples of the ventral blind sac of the rumen for histopathology, immunohistopathology and gene expression. Subjective assessments were made of the presence of lesions on the ruminal wall, the colour of the lining of the ruminal wall and the shape of the ruminal papillae. Almost all variables differed significantly and substantially among farms. Very few pathological changes were detected in any of the rumens examined. The animals on the high-risk diets had lower concentrations of SCFA and higher concentrations of lactate and LPS in the ruminal fluid. Higher LPS concentrations were found in the caecum than the rumen but were not related to the risk status of the farm. The diameters of the stratum granulosum, stratum corneum and of the vasculature of the papillae, and the expression of the gene TLR4 in the ruminal epithelium were all increased on the high-risk farms. The expression of IFN-γ and IL-1β and the counts of cluster of differentiation 3 positive and major histocompatibility complex class two positive cells were lower on the high-risk farms. High among-farm variation and the unbalanced design inherent in this type of study in the field prevented confident assignment of variation in the dependent variables to individual dietary components; however, the CP percentage of the total mixed ration DM was the factor that was most consistently associated with the variables of interest. Despite the strong effect of farm on the measured variables, there was wide inter-animal variation.
OBJECTIVES/SPECIFIC AIMS: o To review the community’s recommendations on how to rebuild trust in the Flint community. o To review effective community engagement strategies utilized with the Flint Special Projects for project conceptualization, participant recruitment, data analysis, project oversight, and dissemination. METHODS/STUDY POPULATION: The study population includes nearly two hundred residents representing seniors, youth and diverse ethnicities recruited to participate in eleven focus group meetings. The population also represents the general public who attended informational meetings in Flint, Michigan to learn about the crisis and allow residents to voice their opinions and concerns during the onset of the crisis. The project is a mixed methods community based participatory research effort that utilized community decision making in all phases of the effort such as pre-conception, implementation, dissemination and advocacy to encourage the community’s recommendations are adopted at policy and institutional responsiveness levels. It includes three community engaged research efforts: (project 1) A qualitative analysis of community sentiment provided during 17 recorded legislative, media and community events, and (projects 2-3) two mixed methods efforts utilizing purposive sampling of stakeholders whose voice may not have been heard. RESULTS/ANTICIPATED RESULTS: The project presents a qualitative analysis of the community’s voice during the onset of the man-made disaster when the community first became aware of the emergency manager’s plans to switch the water source. It also reflects current perspectives of community voice since the projects are scheduled to end late February 2019. Findings from a trust measure administered to nearly two hundred residents will be presented, along with a qualitative analysis of focus group findings among segments of the population (seniors, youth, and diverse ethnicities) who may have been left out of narratives on the water crisis. Finally, the project will compare empowerment and resiliency approaches being utilized in Flint, Michigan to recover from the disaster with other approaches grounded in literature and theory. DISCUSSION/SIGNIFICANCE OF IMPACT: Communities of color often experience social determinants of health which negatively impact their health, well-being and human rights. Some Flint citizens are experiencing negative health consequences (i.e., rashes, brain and behavioral sequelle, fertility, etc.) as a result of the disaster, and are uncertain of health outcomes in the future. This is the first project to rigorously document and analyze levels of trust and mistrust in the city of Flint since the water disaster occurred. The qualitative research will guide future clinical research that will benefit this traumatized community experiencing high levels of mistrust (i.e., government, elected officials, etc.). The community engaged methodology involved residents and study participants in all phases of the project including project oversight, validating and analyzing data, and dissemination. This methodology will contribute to existing literature and theory on community based participatory research, community engaged research, team science and citizen science. The approaches empowered a call to action among residents, for example, seniors who attended two senior focus group sessions shared “they are hopeful and have a purpose,” resulting in the creation of a council (with officers) at their housing complex to advocate for the well-being of seniors during the recovery process. Recruitment methodologies were extremely successful due to resident level trust in community leaders and community partner organizations. Finally, the project’s examination of approaches encouraging empowerment and resiliency will provide lessons learned for other communities challenged with crisis.
This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling.
Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication.
The IPS–WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS–WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS–WFM intervention (45 v. 26 weeks, p < 0.004).
The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.
Objectives: The high rate of cannabis (CAN) use in emerging adults is concerning given prior research suggesting neurocognitive deficits associated with CAN use in youth. Regular CAN use downregulates endocannabinoid activity, while aerobic exercise upregulates cannabinoid receptor 1 activity and releases endocannabinoids. Here we investigate the influence of regular CAN use on neuropsychological performance, and whether aerobic fitness moderates these effects. Methods: Seventy-nine young adults (37 CAN users) aged 16–26 participated. Groups were balanced for aerobic fitness level. Exclusion criteria included: left-handedness, past-year independent Axis-I disorders, major medical/neurologic disorders, prenatal issues, or prenatal alcohol/illicit drug exposure. After 3 weeks of abstinence, participants completed a neuropsychological battery and a maximal oxygen consumption test (VO2 max). Multiple regressions tested whether past-year CAN use, VO2 max, and CAN*VO2 max interaction predicted neuropsychological performance, controlling for past-year alcohol use, cotinine, gender, and depression symptoms. Results: Increased CAN use was associated with decreased performance on working memory and psychomotor tasks. High aerobic fitness level was related to better performance on visual memory, verbal fluency, and sequencing ability. CAN*VO2 max predicted performance of psychomotor speed, visual memory, and sequencing ability. Conclusions: Following monitored abstinence, increased CAN use was associated with poorer performance in working memory and psychomotor speed. Higher aerobic fitness level moderated the impact of CAN on visual memory, executive function and psychomotor speed, as more aerobically fit CAN users demonstrated better performance relative to low-fit users. Therefore, aerobic fitness may present an affordable and efficacious method to improve cognitive functioning in CAN users. (JINS, 2019, 25, 134–145)
Objectives: Past research suggests that youth with sex chromosome aneuploidies (SCAs) present with verbal fluency deficits. However, most studies have focused on sex chromosome trisomies. Far less is known about sex chromosome tetrasomies and pentasomies. Thus, the current research sought to characterize verbal fluency performance among youth with sex chromosome trisomies, tetrasomies, and pentasomies by contrasting how performance varies as a function of extra X number and X versus Y status. Methods: Participants included 79 youth with SCAs and 42 typically developing controls matched on age, maternal education, and racial/ethnic background. Participants completed the phonemic and semantic conditions of a verbal fluency task and an abbreviated intelligence test. Results: Both supernumerary X and Y chromosomes were associated with verbal fluency deficits relative to controls. These impairments increased as a function of the number of extra X chromosomes, and the pattern of impairments on phonemic and semantic fluency differed for those with a supernumerary X versus Y chromosome. Whereas one supernumerary Y chromosome was associated with similar performance across fluency conditions, one supernumerary X chromosome was associated with relatively stronger semantic than phonemic fluency skills. Conclusions: Verbal fluency skills in youth with supernumerary X and Y chromosomes are impaired relative to controls. However, the degree of impairment varies across groups and task condition. Further research into the cognitive underpinnings of verbal fluency in youth with SCAs may provide insights into their verbal fluency deficits and help guide future treatments. (JINS, 2018, 24, 917–927)
OBJECTIVES/SPECIFIC AIMS: Explore perceptions of Flint stakeholders on the water crisis regarding trust and the capacity of faith and community-based organizations providing public health services to address community needs. Analyze the community’s voice shared at (1) 17 key community communications (community/congressional meetings and events), and (2) during 9 focus group sessions, in which residents, faith-based leadership and other stakeholders discuss issues and concerns on the Flint Water Crisis, and recommend ways to address them. Develop a framework that defines core theories, concepts and strategies recommended by the community to help rebuild trust and the quality of life in Flint, Michigan, and support other communities experiencing environmental stress. METHODS/STUDY POPULATION: Study population: faith-based leaders, seniors, youth, Hispanic/Latino and African American stakeholders, and others experiencing inequities in the city of Flint. Convene 9 focus group sessions (recorded and transcribed) to learn community perceptions on trust and ways to address it. Validate accuracy of the transcriptions with community consultants to reconcile any inaccurate information. Through a community engaged research (CEnR) process, review and analyze qualitative data from the 9 focus group sessions, and quantitative data from 2 surveys documenting (1) demographic backgrounds of focus group participants, and (2) their perceptions on trust and mistrust. Prepare a codebook to qualitatively analyze the focus group data summarizing community input on trust, mistrust, changes in service delivery among community and faith-based organizations, and ways to re-build trust in the city of Flint. Transcribe the community’s voice shared during 17 key events, identified by a team of community-academic stakeholders (i.e., UM Flint water course, congressional and community events, etc.), in which residents and other stakeholders discuss issues and concerns on the Flint Water Crisis, and recommend ways to address it. Qualitatively analyze the transcriptions, using a CEnR process to prepare a codebook on key themes from the community’s voice shared at these events, and recommendations on ways to address it. Compare and contrast findings between the two codebooks developed from (1) the focus group data and (2) qualitative analysis of community voice during public meetings and events. Synthesize this information into a framework of core theories, concepts and rebuilding strategies for Flint, Michigan. RESULTS/ANTICIPATED RESULTS: It is important to note many undocumented immigrant populations in Flint fear deportation and other consequences, hampering their ability to obtain service and provide community voice. Through our purposive sampling approach, we will hear from community voices not often included in narratives (i.e., seniors, youth, Hispanic/Latino residents). The presentation will present findings documenting levels of trust and mistrust in the city of Flint; and a framework of recommendations, core theories and concepts on ways to reduce, rebuild and eliminate stress that will be helpful to other communities experiencing distress. DISCUSSION/SIGNIFICANCE OF IMPACT: To our knowledge, levels of trust and mistrust in Flint have not been documented thus far. We will compare and contrast common themes presented by the community at public meetings and events with themes presented in our focus group effort on trust. Faith and community-based providers were among the first responders to the Flint Water Crisis. The effort will also share perceptions on changes in public health service delivery, and observations on preparedness for these roles that occurred among community and faith-based providers. Finally, the effort will (1) support the design of a research agenda, (2) define a framework of core theories, concepts and recommendations developed by the community to help rebuild trust in Flint, Michigan; and (3) support other communities addressing environmental distress.
Survey results suggest that prolonged administration of prophylactic antibiotics is common after mastectomy with reconstruction. We determined utilization, predictors, and outcomes of postdischarge prophylactic antibiotics after mastectomy with or without immediate breast reconstruction.
Commercially insured women aged 18–64 years coded for mastectomy from January 2004 to December 2011 were included in the study. Women with a preexisting wound complication or septicemia were excluded.
Predictors of prophylactic antibiotics within 5 days after discharge were identified in women with 1 year of prior insurance enrollment; relative risks (RR) were calculated using generalized estimating equations.
Overall, 12,501 mastectomy procedures were identified; immediate reconstruction was performed in 7,912 of these procedures (63.3%). Postdischarge prophylactic antibiotics were used in 4,439 procedures (56.1%) with immediate reconstruction and 1,053 procedures (22.9%) without immediate reconstruction (P<.001). The antibiotics most commonly prescribed were cephalosporins (75.1%) and fluoroquinolones (11.1%). Independent predictors of postdischarge antibiotics were implant reconstruction (RR, 2.41; 95% confidence interval [CI], 2.23–2.60), autologous reconstruction (RR, 2.17; 95% CI, 1.93–2.45), autologous reconstruction plus implant (RR, 2.11; 95% CI, 1.92–2.31), hypertension (RR, 1.05; 95% CI, 1.00–1.10), tobacco use (RR, 1.07; 95% CI, 1.01–1.14), surgery at an academic hospital (RR, 1.14; 95% CI, 1.07–1.21), and receipt of home health care (RR, 1.11; 95% CI, 1.04–1.18). Postdischarge prophylactic antibiotics were not associated with SSI after mastectomy with or without immediate reconstruction (both P>.05).
Prophylactic postdischarge antibiotics are commonly prescribed after mastectomy; immediate reconstruction is the strongest predictor. Stewardship efforts in this population to limit continuation of prophylactic antibiotics after discharge are needed to limit antimicrobial resistance.
Few studies have validated ICD-9-CM diagnosis codes for surgical site infection (SSI), and none have validated coding for noninfectious wound complications after mastectomy.
To determine the accuracy of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes in health insurer claims data to identify SSI and noninfectious wound complications, including hematoma, seroma, fat and tissue necrosis, and dehiscence, after mastectomy.
We reviewed medical records for 275 randomly selected women who were coded in the claims data for mastectomy with or without immediate breast reconstruction and had an ICD-9-CM diagnosis code for a wound complication within 180 days after surgery. We calculated the positive predictive value (PPV) to evaluate the accuracy of diagnosis codes in identifying specific wound complications and the PPV to determine the accuracy of coding for the breast surgical procedure.
The PPV for SSI was 57.5%, or 68.9% if cellulitis-alone was considered an SSI, while the PPV for cellulitis was 82.2%. The PPVs of individual noninfectious wound complications ranged from 47.8% for fat necrosis to 94.9% for seroma and 96.6% for hematoma. The PPVs for mastectomy, implant, and autologous flap reconstruction were uniformly high (97.5%–99.2%).
Our results suggest that claims data can be used to compare rates of infectious and noninfectious wound complications after mastectomy across facilities, even though PPVs vary by specific type of postoperative complication. The accuracy of coding was highest for cellulitis, hematoma, and seroma, and a composite group of noninfectious complications (fat necrosis, tissue necrosis, or dehiscence).
Although the authors make strong arguments for both sides of the debate in “Getting Rid of Performance Ratings: Genius or Folly? A Debate,” we argue that performance appraisal reactions were largely overlooked beyond a few exceptions, where the authors either alluded to or explicitly mentioned reactions. For example, the authors explain that one reason organizations have eliminated the forced distribution approach is negative employee reactions. The authors also highlight the importance of managers using appropriate language when delivering performance appraisal ratings in order to improve employee reactions. Despite these exceptions, we believe it is necessary to call more attention to the critical role of ratee reactions in the performance appraisal process. Therefore, our commentary expands on the conversation sparked by Adler et al. (2016) by incorporating ratee reactions.
The herd dynamic milk (HDM) model is a dynamic model capable of simulating the performance of individual dairy animals (from birth to death), with a daily time step. Within this study, the HDM model is described and evaluated in relation to milk production, body condition score (BCS) and BCS change throughout lactation by comparing model simulations against data from published experimental studies. The model’s response to variation in genetic potential, herbage allowance and concentrate supplementation was tested in a sensitivity analysis. Data from experiments in Ireland and France over a 3-year period (2009–11) were used to complete the evaluation. The aim of the Irish experiment was to determine the impact of different stocking rates (SRs) (SR1: 3.28 cow/ha, SR2: 2.51 cow/ha) on key physical, biological and economic performance. The aim of the French experiment was to evaluate over a prolonged time period, the ability of two breeds of dairy cows (Holstein and Normande) to produce and to reproduce under two feeding strategies (high level and low level) in the context of compact calving. The model evaluation was conducted at the herd level with separate evaluations for the primiparous and multiparous cows. The evaluation included the two extreme SRs for the Irish experiment, and an evaluation at the overall herd and individual animal level for the different breeds and feeding levels for the French data. The comparison of simulation and experimental data for all scenarios resulted in a relative prediction error, which was consistently <15% across experiments for weekly milk production and BCS. In relation to BCS, the highest root mean square error was 0.27 points of BCS, which arose for Holstein cows in the low feeding group in late lactation. The model responded in a realistic fashion to variation in genetic potential for milk production, herbage allowance and concentrate supplementation.
The present study aimed to evaluate the precision, ease of use and likelihood of future use of portion size estimation aids (PSEA).
A range of PSEA were used to estimate the serving sizes of a range of commonly eaten foods and rated for ease of use and likelihood of future usage.
For each food, participants selected their preferred PSEA from a range of options including: quantities and measures; reference objects; measuring; and indicators on food packets. These PSEA were used to serve out various foods (e.g. liquid, amorphous, and composite dishes). Ease of use and likelihood of future use were noted. The foods were weighed to determine the precision of each PSEA.
Males and females aged 18–64 years (n 120).
The quantities and measures were the most precise PSEA (lowest range of weights for estimated portion sizes). However, participants preferred household measures (e.g. 200 ml disposable cup) – deemed easy to use (median rating of 5), likely to use again in future (all scored either 4 or 5 on a scale from 1=‘not very likely’ to 5=‘very likely to use again’) and precise (narrow range of weights for estimated portion sizes). The majority indicated they would most likely use the PSEA preparing a meal (94 %), particularly dinner (86 %) in the home (89 %; all P<0·001) for amorphous grain foods.
Household measures may be precise, easy to use and acceptable aids for estimating the appropriate portion size of amorphous grain foods.
We aimed to determine the frequency of qacA/B chlorhexidine tolerance genes and high-level mupirocin resistance among MRSA isolates before and after the introduction of a chlorhexidine (CHG) daily bathing intervention in a surgical intensive care unit (SICU).
Retrospective cohort study (2005–2012)
A large tertiary-care center
Patients admitted to SICU who had MRSA surveillance cultures of the anterior nares
A random sample of banked MRSA anterior nares isolates recovered during (2005) and after (2006–2012) implementation of a daily CHG bathing protocol was examined for qacA/B genes and high-level mupirocin resistance. Staphylococcal cassette chromosome mec (SCCmec) typing was also performed.
Of the 504 randomly selected isolates (63 per year), 36 (7.1%) were qacA/B positive (+) and 35 (6.9%) were mupirocin resistant. Of these, 184 (36.5%) isolates were SCCmec type IV. There was a significant trend for increasing qacA/B (P=.02; highest prevalence, 16.9% in 2009 and 2010) and SCCmec type IV (P<.001; highest prevalence, 52.4% in 2012) during the study period. qacA/B(+) MRSA isolates were more likely to be mupirocin resistant (9 of 36 [25%] qacA/B(+) vs 26 of 468 [5.6%] qacA/B(−); P=.003).
A long-term, daily CHG bathing protocol was associated with a change in the frequency of qacA/B genes in MRSA isolates recovered from the anterior nares over an 8-year period. This change in the frequency of qacA/B genes is most likely due to patients in those years being exposed in prior admissions. Future studies need to further evaluate the implications of universal CHG daily bathing on MRSA qacA/B genes among hospitalized patients.
Having worked on several approaches to CO2 capture over the past decade, we have studied a great number of physical and chemical solvents as well as polymer and composite membranes. Initially, most of these materials were based upon ionic liquids (ILs), however due to challenges encountered in applying ILs to meet the demanding requirements in CO2 separation processes, there is a need to reconsider what role (if any) ILs might play in CO2 capture technologies. Ultimately, more promising and robust materials will not come from ILs themselves, but from retrosynthetic analysis and a reconsideration of which structural variables and properties are (and are not) important. The hybridization of the constituent parts into entirely new, yet seemingly familiar substances, can yield greatly improved properties and economics. This manuscript highlights recent work from our group based on lessons learned from ILs that have spurred the development of new amine solvents and polymer materials to better address the demanding process conditions and requirements of CO2 capture and related separations.
A tooth recovered from the middle Miocene Choptank Formation (Chesapeake Group) of Maryland is identified as a new cynarctin borophagine (Canidae: Borophaginae: Cynarctina), here called Cynarctus wangi n. sp. The tooth, identified as a right upper second molar, represents the first carnivoran material reported from the Choptank Formation and part of a limited record of borophagine canids from eastern North America. As ?Cynarctus marylandica (Berry, 1938), another cynarctin borophagine from the older Calvert Formation, is known only from lower dentition, its generic affinities are uncertain. However, features of this new material are compared to features of ?C. marylandica through occlusal relationships, allowing for referral to a distinct species. Even so, the Choptank Formation material still offers two possible scenarios regarding its identification. In one, its geographic and stratigraphic provenance could imply that it belongs to ?C. marylandica. If this were correct, then the generic placement of ?C. marylandica would be correct and the taxon would be more derived than some other Cynarctus species in regard to hypocarnivory, and less derived than others. The second possibility, and the one believed to be most probable, is that a distinct cynarctin borophagine is present in the Chesapeake Group in strata younger than the type specimen of ?C. marylandica. This new borophagine canid expands the sparse fossil record of this group in northeastern North America and furthers our knowledge of the fossil record of terrestrial taxa in this region.
The Wisconsin Plasma Astrophysics Laboratory (WiPAL) is a flexible user facility designed to study a range of astrophysically relevant plasma processes as well as novel geometries that mimic astrophysical systems. A multi-cusp magnetic bucket constructed from strong samarium cobalt permanent magnets now confines a
, fully ionized, magnetic-field-free plasma in a spherical geometry. Plasma parameters of
provide an ideal testbed for a range of astrophysical experiments, including self-exciting dynamos, collisionless magnetic reconnection, jet stability, stellar winds and more. This article describes the capabilities of WiPAL, along with several experiments, in both operating and planning stages, that illustrate the range of possibilities for future users.
The National Healthcare Safety Network classifies breast operations as clean procedures with an expected 1%–2% surgical site infection (SSI) incidence. We assessed differences in SSI incidence following mastectomy with and without immediate reconstruction in a large, geographically diverse population.
Retrospective cohort study
Commercially insured women aged 18–64 years with ICD-9-CM procedure or CPT-4 codes for mastectomy from January 1, 2004 through December 31, 2011
Incident SSIs within 180 days after surgery were identified by ICD-9-CM diagnosis codes. The incidences of SSI after mastectomy with and without immediate reconstruction were compared using the χ2 test.
From 2004 to 2011, 18,696 mastectomy procedures among 18,085 women were identified, with immediate reconstruction in 10,836 procedures (58%). The incidence of SSI within 180 days following mastectomy with or without reconstruction was 8.1% (1,520 of 18,696). In total, 49% of SSIs were identified within 30 days post-mastectomy, 24.5% were identified 31–60 days post-mastectomy, 10.5% were identified 61–90 days post-mastectomy, and 15.7% were identified 91–180 days post-mastectomy. The incidences of SSI were 5.0% (395 of 7,860) after mastectomy only, 10.3% (848 of 8,217) after mastectomy plus implant, 10.7% (207 of 1,942) after mastectomy plus flap, and 10.3% (70 of 677) after mastectomy plus flap and implant (P<.001). The SSI risk was higher after bilateral compared with unilateral mastectomy with immediate reconstruction (11.4% vs 9.4%, P=.001) than without (6.1% vs 4.7%, P=.021) immediate reconstruction.
SSI incidence was twice that after mastectomy with immediate reconstruction than after mastectomy alone. Only 49% of SSIs were coded within 30 days after operation. Our results suggest that stratification by procedure type facilitates comparison of SSI rates after breast operations between facilities.
This essay is a preliminary sketch for a book that examines Michelangelo Buonarroti’s final eighteen years, from his appointment as architect of St. Peter’s until his death in 1564, that is, from age seventy-one to a few weeks shy of eighty-nine. This period represents nearly a quarter of his approximately seventy-five-year artistic career, yet it remains the least familiar segment of Michelangelo’s long life. It is paradoxical that in the final phase of his career, Michelangelo remained prodigiously creative and influential without being prolific — as he had been earlier in his career. His late life was concerned less with making things than with finding the courage and devotion to continue tasks that he knew he would never see to fruition, and this despite the loss of his closest friends, greatest patron, and his entire family.