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This is the first modern edition of Book X of the Historia Animalium. It argues that the first five chapters are a summary, from the hand of Aristotle, of a medical treatise by a physician practicing in the fourth-century BCE. This gives short shrift to Hippocratic staples such as trapped menses and the wandering womb, and describes a woman's climax during sex in terms that can be easily mapped onto modern accounts. In summarizing the treatise and examining its claims in the last two chapters, Aristotle follows the method described in the Topics for a philosopher embarking on a new field of study. Here we see Aristotle's ruminations over the conundrum of a woman's contribution to conception at an early stage in the development of his theory of reproduction. Far from being an insignificant pseudepigraphon, this is a central text for understanding the development of ancient gynaecology and Aristotelian methodology.
This study estimates the maximum price at which mesenchymal stem cell (MSC) therapy is deemed cost-effective for septic shock patients and identifies parameters that are most important in making treatment decisions.
We developed a probabilistic Markov model according to the sepsis care trajectory to simulate costs and quality-adjusted life years (QALYs) of septic shock patients receiving either MSC therapy or usual care over their lifetime. We calculated the therapeutic headroom by multiplying the gains attributable to MSCs with willingness-to-pay (WTP) threshold and derived the maximum reimbursable price (MRP) from the expected net monetary benefit and savings attributable to MSCs. We performed scenario analyses to assess the impact of changes to assumptions on the study findings. A value of information analysis is performed to identify parameters with greatest impact on the uncertainty around the cost-effectiveness of MSC therapy.
At a WTP threshold of $50,000 per QALY, the therapeutic headroom and MRP of MSC therapy were $20,941 and $16,748, respectively; these estimates increased with the larger WTP values and the greater impact of MSCs on in-hospital mortality and hospital discharge rates. The parameters with greatest information value were MSC's impact on in-hospital mortality and the baseline septic shock in-hospital mortality.
At a common WTP of $50,000/QALY, MSC therapy is deemed to be economically attractive if its unit cost does not exceed $16,748. This ceiling price can be increased to $101,450 if the therapy significantly reduces both in-hospital mortality and increases hospital discharge rates.
The neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression – how age affects clinical presentation in first-episode psychosis – has not been thoroughly investigated.
Using generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naïve individuals with first-episode psychosis (N = 340, 12–40 years, 1–12 visits), collected at the University of Pittsburgh from 1990 to 2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We tested for age-associated effects on change in positive or negative symptom severity following baseline assessment and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development.
Perceptual positive symptom severity significantly decreased with increasing age (F = 7.0, p = 0.0007; q = 0.003) while non-perceptual positive symptom severity increased with age (F = 4.1, p = 0.01, q = 0.02). Anhedonia severity increased with increasing age (F = 6.7, p = 0.00035; q = 0.0003), while flat affect decreased in severity with increased age (F = 9.8, p = 0.002; q = 0.006). Findings remained significant when parental SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (all p > 0.25). Beginning at age 18, there was a statistically significant association between severity of non-perceptual and perceptual symptoms. This relationship increased in strength throughout adulthood.
These findings suggest that as maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced. Findings underscore how pathological brain–behavior relationships vary as a function of development.
Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
This essay looks at the innovations in poetry and poetry publishing from 2001 to 2018, with a particular emphasis on the emerging generation of Indigenous poets like Sherwin Bitsui, Orlando White, Natalie Diaz, and Layli Long Soldier. While paying close attention to the themes and motifs that have been of interest to Native writers, this essay foregrounds innovations in poetic form, including erasures and strikethroughs, complicated syntax, and typographical experimentation. A good deal of recent Native poetry takes on English and its rules and structures as a tool of colonization, repression, identification, and misinformation, and in so doing, seeks to remake English so that it might be viewed through an Indigenous lens.
Heroic activity, titanic struggle, visionary power and similarly exalted descriptions are familiar enough in Beethoven reception. This essay puts those aspects of the composer’s music to one side in order to examine a musical orientation that is derived from the eighteenth-century aesthetic of sociability. Focusing on the composer’s piano sonatas, the essay deals with the interplay between the traditional and the individual in Beethoven’s musical language, an interplay that reveals a versatility of thought that can appropriately be described as gracious.
Currently, no separate service exists for patients with young-onset dementia in Cambridgeshire. These patients are managed together with late-onset dementia patients within old age psychiatry services. To inform service design, we sought to characterise young-onset dementia patients in our population. We first analysed service-level data and supplemented this with a detailed case review of 90 patients.
Young-onset dementia remains a relatively rare condition. Only a small proportion of those referred for assessment receive a diagnosis of dementia. Data collected on presenting complaints, comorbidities, medication and Health of the Nation Outcome Scales scores associated young-onset dementia with a greater incidence of depression than late-onset dementia. Outcomes in the two groups did not appear to differ.
The data presented here do not suggest a need to create a separate service. Practitioners should be aware of the increased incidence of depression observed in this group.
Our recent exploration into the use of biodegradable metals and surface treatments resulting in sufficient strength for skeletal reconstruction applications has led to the need to test these devices’ cytotoxicity. More specifically, our group has developed a resorbable magnesium alloy, Mg–1.2Zn–0.5Ca–0.5Mn, that can be strengthened by heat treatment and coated with a ceramic layer offering time-certain resorption of a medical device. This in vitro study shows that these treatments do not result in cytotoxicity. Both heat-treated (HT) and HT + ceramic-coated (sol–gel) coupons demonstrated more than 70% viability. Thus, these processing steps are likely to be useful in producing biocompatible, resorbable implants that incorporate our Mg–1.2Zn–0.5Ca–0.5Mn alloy.
The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS).
This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers.
In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023).
Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.
Research on the demographic impacts of mining in sparsely populated areas has focused primarily on relatively large towns. Less attention has been paid to smaller villages, which may experience different impacts because of their highly concentrated economies and their small populations, making them more vulnerable to demographic “boom and bust” effects. This paper examines demographic change in four small villages in northern Sweden, which are located close to several mining projects but have evolved through different degrees of integration with or separation from mining. Using a longitudinal “resource cycle” perspective, the demographic trajectories of the villages are compared to understand how different types of settlement and engagement with mining have led to different demographic outcomes in the long term. While the four villages experienced similar trajectories in terms of overall population growth and decline, their experiences in relation to more nuanced indicators, including age and gender distributions and population mobilities, were different, and potential reasons for this are discussed. Due to data limitations, however, the long-term demographic consequences of mining for local Sami people remain unclear. The paper problematises this research gap in light of general concerns about mining impacts on traditional Sami livelihoods.
The current study examines the immediate and short-term impact of daily exposure to community violence on same-day and next-day levels of posttraumatic stress symptomatology and various affective states (i.e., dysphoria, hostility, and anxiety), in a sample of 268 African American adolescents living in urban, low-income, high-violence neighborhoods (Mage = 11.65; 59% female). In addition, the moderating role of affective state variability on this relationship was examined. This study utilized experience sampling method and a daily sampling approach, which contributes a more robust investigation of the short-term effects of violence exposure in youth. Hierarchical linear modeling revealed that community violence exposure was positively associated with same-day and next-day symptoms of posttraumatic stress. Violence exposure also exhibited an immediate effect on dysphoria, anxiety, and hostility levels. Youth variability in dysphoria exacerbated the effect of violence exposure on concurrent or next-day posttraumatic stress, dysphoria, and hostility. Moreover, variability in anxiety and hostility exacerbated the experience of next-day hostility. The clinical implications relating to these findings, such as the importance of implementing screening for posttraumatic stress following exposure, the incorporation of preventative treatments among those at risk of exposure, and the targeting of emotion regulation in treatments with adolescents, are discussed.
OBJECTIVES/GOALS: There is a high burden of lung cancer in persons living with HIV (PLWH). The role that HIV status, by levels of immune function and viral load, has on survival from lung cancer is not fully understood. The study’s objectives were to assess 1) the association of HIV with survival in non-small cell lung cancer (NSCLC) and 2) prognostic factors in PLWH with NSCLC. METHODS/STUDY POPULATION: Participants were from a cohort of lung cancer patients diagnosed between 2004-2017 in the Bronx, NY, with vital status ascertainment at least annually. We compared survival from NSCLC diagnosis between HIV-negative patients (HIV-, N = 2881) and PLWH (N = 88), using Cox regression, accounting for clinical and sociodemographic factors including smoking status. In three separate comparisons to HIV-, PLWH were dichotomized by CD4 count (<200 vs. ≥200 cells/μL), CD4/CD8 ratio (median, <0.43 vs. ≥0.43) and HIV viral load (VL) suppression (<75 vs. ≥75 copies/mL). In PLWH only, we assessed the relationships of CD4 count, CD4/CD8 ratio, and VL at diagnosis with survival adjusting for age, sex, and cancer stage. CD4 count and CD4/CD8 ratio were also examined as time-varying variables using a counting process approach. RESULTS/ANTICIPATED RESULTS: PLWH were younger (median 56 years, IQR 51-52 vs. 68, IQR 60-76) and more likely to be current smokers (58% vs. 37%) at diagnosis than HIV- patients. Median survival was lower in PLWH [1.1 years, 95% confidence interval (95%CI): 0.6-1.3] than in HIV- [1.6 (1.5-1.7)]. Survival comparing PLWH with higher CD4/CD8 to HIV- was similar [hazard ratio (HR), 95%CI: 0.63 (0.37-1.07)], but those with lower CD4/CD8 experienced worse survival (HR = 1.74, 95%CI: 1.07-3.89). Among PLWH, having a CD4 count < 200 cells/μL was associated with over twice the risk of death compared to those with CD4 ≥ 200 cells/μL (HR = 2.37, 95%CI: 1.14-4.92). VL and CD4/CD8 ratio were not associated with survival. Lower time-updated CD4 count was also associated with worse survival (HR = 2.19 for CD4 <200 vs. >200 cells/μL, 95%CI: 1.16-4.13). DISCUSSION/SIGNIFICANCE OF IMPACT: Among persons with NSCLC, CD4/CD8 ratio nearest diagnosis was shown to distinguish mortality risk in PLWH compared with HIV- patients. In addition, PLWH with low CD4 had worse prognosis than PLWH who had higher CD4 counts. These results suggest HIV immune status to be an essential component influencing survival in lung cancer.