Acute oral toxicity of zinc phosphide: an assessment for wild house mice (Mus musculus).

Irregular plagues of house mice, Mus musculus, incur major economic impacts on agricultural production in Australia. The efficacy of zinc phosphide (ZnP), the only registered broadacre control agent for mice, is reported as increasingly variable. Have mice become less sensitive over time or are they taking a sub-lethal dose and developing aversion? In this laboratory study, the sensitivity of mice (wild caught; outbred laboratory strain) was assessed using oral gavage of a range of ZnP concentrations. The estimated LD50 values (72-79 mg ZnP/kg body weight) were similar for each mouse group but are significantly higher than previously reported. The willingness of mice to consume ZnP-coated grains was determined. ZnP-coated grains (50 g ZnP/kg grain) presented in the absence of alternative food were consumed and 94% of wild mice died. Mice provided with alternative food and ZnP-coated wheat grains (either 25 or 50 g ZnP/kg grain) consumed toxic and non-toxic grains, and mortality was lower (33-55%). If a sublethal amount of ZnP-coated grain was consumed, aversion occurred, mostly when alternative food was present. The sensitivity of wild house mice to ZnP in Australia is significantly lower than previously assumed. Under laboratory conditions, ZnP-coated grains coated with a new higher dose (50 g ZnP/kg grain) were readily consumed. Consumption of toxic grain occurred when alternative food was available but was decreased. Our unambiguous findings for house mice indicate a re-assessment of the ZnP loading for baits used for control of many rodents around the world may be warranted.

The anthropology of health systems: A history and review.

Ethnographies of health systems are a theoretically rich and rapidly growing area within medical anthropology. Critical ethnographic work dating back to the 1950s has taken policymakers and health staff as points of entry into the power structures that run through the global health enterprise. In the last decade, there has been a surge of ethnographic work on health systems. We conceptualize the anthropology of health systems as a field; review the history of this body of knowledge; and outline emergent literatures on policymaking, HIV, hospitals, Community Health Workers, health markets, pharmaceuticals, and metrics. High-quality ethnographic work is an excellent way to understand the complex systems that shape health outcomes, and provides a critical vantage point for thinking about global health policy and systems. As theory in this space develops and deepens, we argue that anthropologists should look beyond the discipline to think through what their work does and why it matters.

Application of Machine Learning Using Decision Trees for Prognosis of Deep Brain Stimulation of Globus Pallidus Internus for Children With Dystonia.

BACKGROUND: While Deep Brain Stimulation (DBS) of the Globus pallidus internus is a well-established therapy for idiopathic/genetic dystonia, benefits for acquired dystonia are varied, ranging from modest improvement to deterioration. Predictive biomarkers to aid DBS prognosis for children are lacking, especially in acquired dystonias, such as dystonic Cerebral Palsy. We explored the potential role of machine learning techniques to identify parameters that could help predict DBS outcome. METHODS: We conducted a retrospective study of 244 children attending King's College Hospital between September 2007 and June 2018 for neurophysiological tests as part of their assessment for possible DBS at Evelina London Children's Hospital. For the 133 individuals who underwent DBS and had 1-year outcome data available, we assessed the potential predictive value of six patient parameters: sex, etiology (including cerebral palsy), baseline severity (Burke-Fahn-Marsden Dystonia Rating Scale-motor score), cranial MRI and two neurophysiological tests, Central Motor Conduction Time (CMCT) and Somatosensory Evoked Potential (SEP). We applied machine learning analysis to determine the best combination of these features to aid DBS prognosis. We developed a classification algorithm based on Decision Trees (DTs) with k-fold cross validation for independent testing. We analyzed all possible combinations of the six features and focused on acquired dystonias. RESULTS: Several trees resulted in better accuracy than the majority class classifier. However, the two features that consistently appeared in top 10 DTs were CMCT and baseline dystonia severity. A decision tree based on CMCT and baseline severity provided a range of sensitivity and specificity, depending on the threshold chosen for baseline dystonia severity. In situations where CMCT was not available, a DT using SEP alone provided better than the majority class classifier accuracy. CONCLUSION: The results suggest that neurophysiological parameters can help predict DBS outcomes, and DTs provide a data-driven, highly interpretable decision support tool that lends itself to being used in clinical practice to help predict potential benefit of DBS in dystonic children. Our results encourage the introduction of neurophysiological parameters in assessment pathways, and data collection to facilitate multi-center evaluation and validation of these potential predictive markers and of the illustrative decision support tools presented here.

Teaching Health as a Human Right in the Undergraduate Context: Challenges and Opportunities.

This paper explores the possibility of a pedagogy about health and human rights that is understandable and persuasive to undergraduate students yet does not succumb to a reductive dualism of optimism and pessimism. In 2014, we presented the topic of health and human rights in an introductory undergraduate global health course in conjunction with the exhibit "Health is a Human Right: Race and Place in America" at the Centers for Disease Control in Atlanta, Georgia. The exhibition highlighted the United States' complicated legacy and failures of health and human rights, with an emphasis on ongoing racial and socioeconomic inequities. In conjunction with class lectures, students viewed the exhibit and submitted a survey and a reflective essay about human rights abuses, as well as possibilities for realizing the right to health in the United States. Contrary to our expectations, the human rights issues surrounding the AIDS epidemic raised very little interest among our students, for whom AIDS is a preventable and treatable chronic disease. Instead, students were most interested in exhibits on eugenics and forced sterilization, deficits in water and sanitation, racism, and contradictions of American exceptionalism. We conclude that an emphasis on the violations of human rights and their health effects using domestic examples from relatively recent history can be an effective pedagogical strategy. This approach represents an opportunity to counter students' presumptions that the United States exists outside of the human rights discourse. Moreover, this approach may reinforce the idea that the domestic race- and class-based inequalities can and should be understood as human rights violations.

Treatment intensity and survival in patients with relapsed or refractory diffuse large B-cell lymphoma in Denmark: a real-life population-based study.

PURPOSE: High-dose chemotherapy with autologous stem cell transplantation (ASCT) is considered to be the only curative treatment option for patients with refractory or relapsed diffuse large B-cell lymphoma (DLBCL). Due to toxicity, not all patients are eligible for this treatment leading to different treatment intensities. Here, we aim to analyze the impact of treatment intensity on survival in patients previously treated with rituximab and chemotherapy, and, furthermore, to analyze the association between socioeconomic position and treatment intensity, defined as palliation, non-salvage, and salvage regimens. MATERIALS AND METHODS: We identified patients with refractory or relapsed DLBCL diagnosed in 2000-2015 in the Danish National Lymphoma Registry (n=1,228). We analyzed the impact of treatment intensity on survival in patients previously treated with rituximab (n=277) using a Cox proportional hazards model. Multinomial regression analyses were performed to identify associations between socioeconomic factors and treatment intensity for the entire cohort. RESULTS: In the rituximab era, the 5-year overall survival (OS) was 31% for patients receiving salvage regimens (n=194), and 17% for patients receiving non-salvage regimens (n=83). In the adjusted analysis, HR was 1.88, 95% CI: 0.9-3.9 for patients receiving salvage regimens. Patients living alone were significantly less likely to receive salvage regimens, as were patients with two or more comorbidities. CONCLUSION: We observed a better OS in patients treated with salvage regimens compared with non-salvage regimens; however, the adjusted analysis contradicts this. Furthermore, our results indicate that there is a chance of remission for patients not eligible for ASCT.

Integrated versus nOn-integrated Peripheral inTravenous catheter. Which Is the most effective systeM for peripheral intravenoUs catheter Management? (The OPTIMUM study): a randomised controlled trial protocol.

INTRODUCTION: Peripheral intravenous catheters (PIVCs) are frequently used in hospitals. However, PIVC complications are common, with failures leading to treatment delays, additional procedures, patient pain and discomfort, increased clinician workload and substantially increased healthcare costs. Recent evidence suggests integrated PIVC systems may be more effective than traditional non-integrated PIVC systems in reducing phlebitis, infiltration and costs and increasing functional dwell time. The study aim is to determine the efficacy, cost-utility and acceptability to patients and professionals of an integrated PIVC system compared with a non-integrated PIVC system. METHODS AND ANALYSIS: Two-arm, multicentre, randomised controlled superiority trial of integrated versus non-integrated PIVC systems to compare effectiveness on clinical and economic outcomes. Recruitment of 1560 patients over 2 years, with randomisation by a centralised service ensuring allocation concealment. Primary outcomes: catheter failure (composite endpoint) for reasons of: occlusion, infiltration/extravasation, phlebitis/thrombophlebitis, dislodgement, localised or catheter-associated bloodstream infections. SECONDARY OUTCOMES: first time insertion success, types of PIVC failure, device colonisation, insertion pain, functional dwell time, adverse events, mortality, cost-utility and consumer acceptability. One PIVC per patient will be included, with intention-to-treat analysis. Baseline group comparisons will be made for potentially clinically important confounders. The proportional hazards assumption will be checked, and Cox regression will test the effect of group, patient, device and clinical variables on failure. An as-treated analysis will assess the effect of protocol violations. Kaplan-Meier survival curves with log-rank tests will compare failure by group over time. Secondary endpoints will be compared between groups using parametric/non-parametric techniques. ETHICS AND DISSEMINATION: Ethical approval from the Royal Brisbane and Women's Hospital Human Research Ethics Committee (HREC/16/QRBW/527), Griffith University Human Research Ethics Committee (Ref No. 2017/002) and the South Metropolitan Health Services Human Research Ethics Committee (Ref No. 2016-239). Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12617000089336.

Simplicity at the cost of predictive accuracy in diffuse large B-cell lymphoma: a critical assessment of the R-IPI, IPI, and NCCN-IPI.

The international prognostic index (IPI) and similar models form the cornerstone of clinical assessment in newly diagnosed diffuse large B-cell lymphoma (DLBCL). While being simple and convenient to use, their inadequate use of the available clinical data is a major weakness. In this study, we compared performance of the International Prognostic Index (IPI) and its variations (R-IPI and NCCN-IPI) to a Cox proportional hazards (CPH) model using the same covariates in nondichotomized form. All models were tested in 4863 newly diagnosed DLBCL patients from population-based Nordic registers. The CPH model led to a substantial increase in predictive accuracy as compared to conventional prognostic scores when evaluated by the area under the curve and other relevant tests. Furthermore, the generation of patient-specific survival curves rather than assigning patients to one of few predefined risk groups is a relevant step toward personalized management and treatment. A test-version is available on lymphomapredictor.org.

Preexisting Cardiovascular Risk and Subsequent Heart Failure Among Non-Hodgkin Lymphoma Survivors.

Purpose The use of anthracycline chemotherapy is associated with heart failure (HF) among survivors of non-Hodgkin lymphoma (NHL). We aimed to understand the contribution of preexisting cardiovascular risk factors to HF risk among NHL survivors. Methods Using Danish registries, we identified adults diagnosed with aggressive NHL from 2000 to 2010 and sex- and age-matched general-population controls. We assessed HF from 9 months after diagnosis through 2012. We used Cox regression analysis to assess differences in risk for HF between survivors and general population controls. Among survivors only, preexisting cardiovascular factors (hypertension, dyslipidemia, and diabetes) and preexisting cardiovascular disease were ascertained. We used multivariable Cox regression to model the association of preexisting cardiovascular conditions on subsequent HF. Results Among 2,508 survivors of NHL and 7,399 controls, there was a 42% increased risk of HF among survivors compared with general population controls (hazard ratio [HR], 1.42; 95% CI, 1.07 to 1.88). Among survivors (median age at diagnosis, 62 years; 56% male), 115 were diagnosed with HF during follow-up (median years of follow-up, 2.5). Before NHL diagnosis, 39% had ≥ 1 cardiovascular risk factor; 92% of survivors were treated with anthracycline-containing regimens. In multivariable analysis, intrinsic heart disease diagnosed before lymphoma was associated with increased risk of HF (HR, 2.71; 95% CI, 1.15 to 6.36), whereas preexisting vascular disease had no association with HF ( P > .05). Survivors with cardiovascular risk factors had an increased risk of HF compared with those with none (for 1 v 0 cardiovascular risk factors: HR, 1.63; 95% CI, 1.07 to 2.47; for ≥ 2 v 0 cardiovascular risk factors: HR, 2.86; 95% CI, 1.56 to 5.23; joint P < .01). Conclusion In a large, population-based cohort of NHL survivors, preexisting cardiovascular conditions were associated with increased risk of HF. Preventive approaches should take baseline cardiovascular health into account.

Anthropologists in MalariaWorld.

The history of anthropological contributions to the study of malaria is reviewed in terms of three additive phases: (1) cultural-historical analyses; (2) applied work aimed at the improvement of malaria control programs; and (3) introduction of critical medical anthropological themes about malaria control. The critical approaches include themes of the cultural construction of reality-the definition of "malaria"; political-economic structures in health inequalities; and an emphasis on social factors as exemplified in the present special issue. The contemporary culture of malaria researchers and programs-called MalariaWorld-is described in terms of economy, social organization, and belief system. Five common features of articles in this special issue are described as unique anthropological features that are key for understanding MalariaWorld.

Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank.

The annual Deep Brain Stimulation (DBS) Think Tank provides a focal opportunity for a multidisciplinary ensemble of experts in the field of neuromodulation to discuss advancements and forthcoming opportunities and challenges in the field. The proceedings of the fifth Think Tank summarize progress in neuromodulation neurotechnology and techniques for the treatment of a range of neuropsychiatric conditions including Parkinson's disease, dystonia, essential tremor, Tourette syndrome, obsessive compulsive disorder, epilepsy and cognitive, and motor disorders. Each section of this overview of the meeting provides insight to the critical elements of discussion, current challenges, and identified future directions of scientific and technological development and application. The report addresses key issues in developing, and emphasizes major innovations that have occurred during the past year. Specifically, this year's meeting focused on technical developments in DBS, design considerations for DBS electrodes, improved sensors, neuronal signal processing, advancements in development and uses of responsive DBS (closed-loop systems), updates on National Institutes of Health and DARPA DBS programs of the BRAIN initiative, and neuroethical and policy issues arising in and from DBS research and applications in practice.

The human subthalamic nucleus encodes the subjective value of reward and the cost of effort during decision-making.

Adaptive behaviour entails the capacity to select actions as a function of their energy cost and expected value and the disruption of this faculty is now viewed as a possible cause of the symptoms of Parkinson's disease. Indirect evidence points to the involvement of the subthalamic nucleus-the most common target for deep brain stimulation in Parkinson's disease-in cost-benefit computation. However, this putative function appears at odds with the current view that the subthalamic nucleus is important for adjusting behaviour to conflict. Here we tested these contrasting hypotheses by recording the neuronal activity of the subthalamic nucleus of patients with Parkinson's disease during an effort-based decision task. Local field potentials were recorded from the subthalamic nucleus of 12 patients with advanced Parkinson's disease (mean age 63.8 years ± 6.8; mean disease duration 9.4 years ± 2.5) both OFF and ON levodopa while they had to decide whether to engage in an effort task based on the level of effort required and the value of the reward promised in return. The data were analysed using generalized linear mixed models and cluster-based permutation methods. Behaviourally, the probability of trial acceptance increased with the reward value and decreased with the required effort level. Dopamine replacement therapy increased the rate of acceptance for efforts associated with low rewards. When recording the subthalamic nucleus activity, we found a clear neural response to both reward and effort cues in the 1-10 Hz range. In addition these responses were informative of the subjective value of reward and level of effort rather than their actual quantities, such that they were predictive of the participant's decisions. OFF levodopa, this link with acceptance was weakened. Finally, we found that these responses did not index conflict, as they did not vary as a function of the distance from indifference in the acceptance decision. These findings show that low-frequency neuronal activity in the subthalamic nucleus may encode the information required to make cost-benefit comparisons, rather than signal conflict. The link between these neural responses and behaviour was stronger under dopamine replacement therapy. Our findings are consistent with the view that Parkinson's disease symptoms may be caused by a disruption of the processes involved in balancing the value of actions with their associated effort cost.

Participatory monitoring and evaluation to aid investment in natural resource manager capacity at a range of scales.

Natural resource (NR) outcomes at catchment scale rely heavily on the adoption of sustainable practices by private NR managers because they control the bulk of the NR assets. Public funds are invested in capacity building of private landholders to encourage adoption of more sustainable natural resource management (NRM) practices. However, prioritisation of NRM funding programmes has often been top-down with limited understanding of the multiple dimensions of landholder capacity leading to a failure to address the underlying capacity constraints of local communities. We argue that well-designed participatory monitoring and evaluation of landholder capacity can provide a mechanism to codify the tacit knowledge of landholders about the social-ecological systems in which they are embedded. This process enables tacit knowledge to be used by regional NRM bodies and government agencies to guide NRM investment in the Australian state of New South Wales. This paper details the collective actions to remove constraints to improved NRM that were identified by discrete groups of landholders through this process. The actions spanned geographical and temporal scales, and responsibility for them ranged across levels of governance.

Positron emission tomography/computed tomography surveillance in patients with Hodgkin lymphoma in first remission has a low positive predictive value and high costs.

BACKGROUND: The value of performing post-therapy routine surveillance imaging in patients with Hodgkin lymphoma is controversial. This study evaluates the utility of positron emission tomography/computed tomography using 2-[18F]fluoro-2-deoxyglucose for this purpose and in situations with suspected lymphoma relapse. DESIGN AND METHODS: We conducted a multicenter retrospective study. Patients with newly diagnosed Hodgkin lymphoma achieving at least a partial remission on first-line therapy were eligible if they received positron emission tomography/computed tomography surveillance during follow-up. Two types of imaging surveillance were analyzed: "routine" when patients showed no signs of relapse at referral to positron emission tomography/computed tomography, and "clinically indicated" when recurrence was suspected. RESULTS: A total of 211 routine and 88 clinically indicated positron emission tomography/computed tomography studies were performed in 161 patients. In ten of 22 patients with recurrence of Hodgkin lymphoma, routine imaging surveillance was the primary tool for the diagnosis of the relapse. Extranodal disease, interim positron emission tomography-positive lesions and positron emission tomography activity at response evaluation were all associated with a positron emission tomography/computed tomography-diagnosed preclinical relapse. The true positive rates of routine and clinically indicated imaging were 5% and 13%, respectively (P = 0.02). The overall positive predictive value and negative predictive value of positron emission tomography/computed tomography were 28% and 100%, respectively. The estimated cost per routine imaging diagnosed relapse was US$ 50,778. CONCLUSIONS: Negative positron emission tomography/computed tomography reliably rules out a relapse. The high false positive rate is, however, an important limitation and a confirmatory biopsy is mandatory for the diagnosis of a relapse. With no proven survival benefit for patients with a pre-clinically diagnosed relapse, the high costs and low positive predictive value make positron emission tomography/computed tomography unsuitable for routine surveillance of patients with Hodgkin lymphoma.

Assessment of early diastolic strain-velocity temporal relationships using spatial modulation of magnetization with polarity alternating velocity encoding (SPAMM-PAV).

A novel MR imaging technique, spatial modulation of magnetization with polarity alternating velocity encoding (SPAMM-PAV), is presented to simultaneously examine the left ventricular early diastolic temporal relationships between myocardial deformation and intra-cavity hemodynamics with a high temporal resolution of 14 ms. This approach is initially evaluated in a dynamic flow and tissue mimicking phantom. A comparison of regional longitudinal strains and intra-cavity pressure differences (integration of computed in-plane pressure gradients within a selected region) in relation to mitral valve inflow velocities is performed in eight normal volunteers. Our results demonstrate that apical regions have higher strain rates (0.145 ± 0.005 %/ms) during the acceleration period of rapid filling compared to mid-ventricular (0.114 ± 0.007 %/ms) and basal regions (0.088 ± 0.009 %/ms), and apical strain curves plateau at peak mitral inflow velocity. This pattern is reversed during the deceleration period, when the strain-rates in the basal regions are the highest (0.027 ± 0.003 %/ms) due to ongoing basal stretching. A positive base-to-apex gradient in peak pressure difference is observed during acceleration, followed by a negative base-to-apex gradient during deceleration. These studies shed insight into the regional volumetric and pressure difference changes in the left ventricle during early diastolic filling.

Socioeconomic inequalities in prognostic markers of non-Hodgkin lymphoma: analysis of a national clinical database.

The survival of non-Hodgkin lymphoma patients strongly depends on a range of prognostic factors. This registry-based clinical cohort study investigates the relation between socioeconomic position and prognostic markers in 6234 persons included in a national clinical database in 2000-2008, Denmark. Several measures of individual socioeconomic position were achieved from Statistics Denmark. The risk of being diagnosed with advanced disease, as expressed by the six prognostic markers (Ann Arbor stage III or IV, more than one extranodal lesion, elevated serum lactate dehydrogenase (LDH), performance status of two or more, presence of B symptoms and International Prognostic Index (IPI) of two or more), increased with decreasing level of education, in patients living alone, and in men. For instance, a significant decrease in the odds of being diagnosed with elevated LDH (p=0.02), high performance status (p=0.004), high IPI score (p=0.004) and B symptoms (p=0.02) was seen with higher level of education, whereas high stage of disease was significantly less likely in the higher educated (odds ratio [OR]=0.85 (0.74-0.99)). The difference in risk seemed not to be mediated by differences in histological subgroups reflecting aggressiveness of disease among the social groups. One of the most likely mechanisms of the social difference is longer delay in those with low socioeconomic position. The findings of social inequality in prognostic markers in non-Hodgkin lymphoma (NHL) patients could already be implemented in the clinical practice if general practitioners (GP's) and physicians on hospitals paid special attention to patients with low educational level and unspecific symptoms.

Idiopathic spinal myoclonus: a clinical and neurophysiological assessment of a movement disorder of uncertain origin.

Spinal Myoclonus (SM) is characterized by brief and sudden movements caused by the activation of muscles belonging to adjacent spinal myotomes. Recent reports have indicated that "typical" clinical and electrophysiological features of SM can be mimicked voluntarily. A useful tool that can distinguish between organic and psychogenic jerks is the detection of a Bereitschaftspotential (BP). In this study, we looked for evidence of a BP in a cohort of patients with idiopathic SM. A clinical and neurophysiological assessment of 20 patients affected by idiopathic SM was performed. A video EEG-EMG multichannel recording was performed in each patient to detect BP. An expert neurophysiologist (PB) reviewed the BP recordings and divided them into those showing a definite, possible, and no BP. A clinical assessment of the videoed movements was performed by two neurologists expert in movement disorders (KB and MJE) who indicated if the movements were compatible with organic or psychogenic myoclonus. A definite or possible BP was recorded in 15 out of 20 patients. Clinical raters agreed in their clinical opinion on 15 patients (75%). All patients where both raters agreed the movements appeared to be organic had definite or possible BP. BP are commonly seen in patients with idiopathic SM. There is discordance between clinicians in their clinical rating of SM as organic or psychogenic, but even in those patients where movements appear clinically to be organic, a BP is commonly detected, indicating that the aetiology is psychogenic. This suggests that BP recordings are a useful adjunct to clinical assessment in the accurate diagnosis of patients with idiopathic SM.

Existing motor state is favored at the expense of new movement during 13-35 Hz oscillatory synchrony in the human corticospinal system.

Oscillations in local field potentials in the beta-frequency band (13-35 Hz) are a pervasive feature of human and nonhuman primate motor cortical areas. However, the function of such synchronous activity across populations of neurons remains unknown. Here, we test the hypothesis that beta activity may promote existing motor set and posture while compromising processing related to new movements. Three experiments were performed. First, healthy subjects were instructed to make reaction time movements of the outstretched index finger in response to imperative cues triggered by transient increases in corticospinal synchrony, as evidenced by phasic elevations of beta-frequency band microtremor and intermuscular synchrony. Second, healthy subjects were instructed to resist a stretch to the index finger triggered in the same way. Finger acceleration in the reaction time task and transcortical components of the stretch reflex were measured and compared with those elicited by random cue or stretch presentation. Finally, we sought a correlation between finger acceleration in the reaction time task and cortical synchrony directly measured from the electrocorticogram in two patients undergoing functional neurosurgery. We demonstrate that movements are slowed and transcortical responses to stretch are potentiated during periods of elevated beta-band cortical synchrony. The results suggest that physiological periods of beta synchrony are associated with a cortical state in which postural set is reinforced, but the speed of new movements impaired. The findings are of relevance to Parkinson's disease, in which subcortical and cortical beta-band synchronization is exaggerated in the setting of increased tone and slowed movements.

Evolutionary, historical and political economic perspectives on health and disease.

The origin and rise of social inequalities that are a feature of the post-Neolithic society play a major role in the pattern of disease in prehistoric and contemporary populations. We use the concept of epidemiological transition to understand changing ecological relationships between humans, pathogens and other disease insults. With the Paleolithic period as a baseline, we begin with ecological and social relationships that minimized the impact of infectious disease. Paleolithic populations would have retained many of the pathogens that they shared with their primate ancestors and would have been exposed to zoonoses that they picked up as they adapted to a foraging existence. The sparse mobile populations would have precluded the existence of endemic infectious disease. About 10,000 years ago, the shift to an agricultural subsistence economy created the first epidemiological transition, marked by the emergence of infections, a pattern that has continued to the present. Beginning about a century ago, some populations have undergone a second epidemiological transition in which public health measures, improved nutrition and medicine resulted in declines in infectious disease and a rise in non-infectious, chronic and degenerative diseases. Human populations are entering the third epidemiological transition in which there is a reemergence of infectious diseases previously thought to be under control, and the emergence of novel diseases. Many of the emerging and reemerging pathogens are antibiotic resistant and some are multi-antibiotic resistant. Inequality continues to widen within and between societies, accelerating the spread of emerging and reemerging diseases.