A Possible Mechanism of Laryngohyoid Fractures in Hanging: A Preliminary Observation.

ABSTRACT: Fractures of the hyoid bone, particularly the greater horns, and thyroid cartilage (superior horns) are known to be associated with hanging deaths. Depending on the literature, the frequency of these fractures varies from 0% to 83%. The mechanism underlying these fractures is believed to be direct compression or indirect traction from the ligature. The relationship of these structures with the cervical spine cannot be visualized with traditional internal examination, due to obstruction by surrounding soft tissue. Postmortem computed tomography scan offers an unobscured view of the relationship of the laryngohyoid structures with the cervical spine.We aim to illustrate the phenomenon of displacement of the laryngohyoid structures associated with fractures of the horns. In our case reports, the laryngohyoid structures were displaced, not only superiorly and posteriorly, but also in 2 of the cases, by tilting, when the suspension point was at the posterior or posterolateral aspect of the neck. This displacement had caused the greater horns of the hyoid bone and superior horns of the thyroid cartilage to be approximated against the cervical spine, particularly the transverse processes. We believe that, in these circumstances, the fractures were caused by pressure of the horns of the laryngohyoid structures against the cervical spine.

Utility of 68Ga-DOTATATE PET-MRI for Gamma Knife® stereotactic radiosurgery treatment planning for meningioma.

OBJECTIVES: To investigate the impact of adding 68Ga-DOTATATE PET/MRI to standard MRI for target volume delineation in Gamma Knife® stereotactic radiosurgery (GKSRS) for meningioma. METHODS: Seventeen patients with 18 lesions undergoing GKSRS for WHO grade 1 meningioma were enrolled in a prospective study. All patients underwent pre-treatment 68Ga-DOTATATE PET/MRI examination in addition to standard procedures. Five clinicians independently contoured the gross tumour volume (GTV) based on standard MRI (GTVMRI) and PET/MRI (GTVPET/MRI) on separate occasions. Interobserver agreement was evaluated using Cohen's Kappa statistic (CKS), Dice similarity coefficient (DC), and Hausdorff distance (HD). Statistical analysis was performed with paired t-test and Wilcoxon signed rank test. RESULTS: The addition of PET/MRI significantly increased GTV contour volume (mean GTVPET/MRI 3.59 cm3 versus mean GTVMRI 3.18 cm3, P = .008). Using the treating clinician's pre-treatment GTVMRI as the reference, median CKS (87.2 vs 77.5, P = .006) and DC (87.2 vs 77.4, P = .006) were significantly lower, and median HD (25.2 vs 31.0, P = .001) was significantly higher with the addition of PET/MRI. No significant difference was observed in interobserver contouring reproducibility between GTVMRI and GTVPET/MRI. CONCLUSION: The addition of 68Ga-DOTATATE PET/MRI for target volume delineation in GKSRS for meningioma is associated with an increase in GTV volume and greater interobserver variation. PET/MRI did not affect interobserver contouring reproducibility. ADVANCES IN KNOWLEDGE: This study provides novel insights into the impact of 68Ga-DOTATATE PET/MRI on GTV delineation and interobserver agreement in meningioma GKSRS, highlighting its potential for improving GKSRS treatment accuracy.

Susceptibility weighted imaging for qualitative grading of persistent arteriovenous shunting in deep-seated arteriovenous malformations after stereotactic radiation surgery.

BACKGROUND AND PURPOSE: To investigate Susceptibility Weighted Imaging (SWI) signal changes in the draining vein of deep-seated arterio-venous malformations (AVMs) following stereotactic radiosurgery (SRS). METHODS AND MATERIALS: This is a retrospective study of 32 patients with deep-seated AVMs who were treated with SRS. Pre-SRS treatment and post-SRS treatment MRI were performed at 6, 12, and 24-month intervals. Deep-seated AVMs were classified based on their anatomical location and venous drainage pattern. AVM nidal volume (cm3) was estimated using the ABC/2 method. AV shunting of the AVM draining veins were graded according to its SWI signal intensity: hyperintense (grade III), mixed signal intensity (grade II), hypointense (grade I) and absent (grade 0). Conventional time-of-flight (TOF)-MRA and contrast enhanced (CE)-MRA sequences were performed to document the patency of the vein. RESULTS: Pre-SRS treatment AVM draining veins were either grade III 18/32 (56%) or grade II 14/32 (44%). Using mixed effects analysis, we demonstrate that each month following the SRS treatment nidal volumes decreased at the rate of 0.51 cm3/per month (CI -0.61 to (-0.40)) p =.00. Following the treatment, there was a clinically significant relationship between the signal and nidal volume: signal 0 corresponded with average nidal volume of 1.81 cm3 (CI 1.40-2.21), signal 1 with nidal volume of 2.06 cm3 (CI 1.69-2.44), signal 2 with nidal volume 2.73 cm3 (CI 2.35-3.11) and signal 3 with nidal volume 3.13 cm3 (CI 2.70-3.56) p = .00. CONCLUSION: Post-SRS AVM draining veins shows a stepwise regression of the SWI signal grades which can be reliably used as a surrogate to monitor the reduction of AV shunting.

Gamma Knife® stereotactic radiosurgery for intracranial cavernous malformations.

INTRODUCTION: Gamma Knife® stereotactic radiosurgery (GKSRS) is a non-invasive alternative to surgical resection for cerebral cavernous malformations (CCMs), especially in eloquent locations. METHODOLOGY: A retrospective review was performed on an Australian cohort of patients receiving GKSRS for CCMs at a single institution. All patients exhibited symptoms and/or radiological evidence of haemorrhage before therapy. The minimum follow-up was 1-year post-GKSRS. McNemar's test was used for differences in matched-pair outcomes pre- and post-GKSRS with an α = 0.05. A systematic review and meta-analysis was additionally performed to synthesise the current published evidence on the clinical efficacy of stereotactic radiosurgery in reducing haemorrhage risk in CCMs using a DerSimonian and Laird random effects model. RESULTS: Thirty-five patients (39 cavernomas) underwent GKSRS. 87.2 % of patients had evidence of at least one haemorrhage before GKSRS and the remainder exhibited seizures. The median dose was 12.5 Gy in a single fraction (IQR 12-13). The median follow-up duration from GKSRS was 809 days (IQR 536-960). There was a significant reduction in matched annual bleed rate from pre-GKSRS (52.1 %) compared to after SRS (12.3 %) (p < 0.001) [OR = 0.07, 95 % 0.008-0.283] There was no statistically significant difference in seizure incidence pre- (30.7 %) versus post-GKSRS (17.9 %) (p = 0.13) [OR = 0.167, 95 %CI 0.004-1.37]. One patient (3 %) with a brainstem lesion experienced long-term treatment-related oedema with persistent ipsilateral weakness and tremors. On meta-analysis of 25 pooled studies, radiosurgery for the treatment of CCMs was associated with a statistically significantly relative risk (RR) reduction in haemorrhage events [random effects RR 0.12 (95 % CI 0.074-0.198), p < 0.001)], with most of the proportionate risk reduction occurring in the initial 2 years following SRS. CONCLUSION: GKSRS significantly reduces the annual rate of haemorrhage for intracranial cavernomas in this cohort and on meta-analysis, particularly in the first 2 years following treatment. The overall risk of treatment-related morbidity is low.

Gene expression of sex steroid metabolizing enzymes and receptors in the skeletal muscle of migrant and resident subspecies of white-crowned sparrow (Zonotrichia leucophrys).

Circulating sex steroid concentrations vary dramatically across the year in seasonally breeding animals. The ability of circulating sex steroids to effect muscle function can be modulated by changes in intracellular expression of steroid metabolizing enzymes (e.g., 5α-reductase type 2 and aromatase) and receptors. Together, these combined changes in plasma hormones, metabolizing enzymes and receptors allow for seasonally appropriate changes in skeletal muscle function. We tested the hypothesis that gene expression of sex steroid metabolizing enzymes and receptors would vary seasonally in skeletal muscle and these changes would differ between a migrant and resident life history strategy. We quantified annual changes in plasma testosterone and gene expression in pectoralis and gastrocnemius skeletal muscles using quantitative polymerase chain reaction (qPCR) in free-living migrant (Zonotrichia leucophrys gambelii) and resident (Z. l. nuttalli) subspecies of white-crowned sparrow during breeding, pre-basic molt, and wintering life history stages. Pectoralis muscle profile was largest in migrants during breeding, while residents maintained large muscle profiles year-round. Circulating testosterone peaked during breeding in both subspecies. Pectoralis muscle androgen receptor mRNA expression was lower in females of both subspecies during breeding. Estrogen receptor-α expression was higher in the pectoralis muscle, but not gastrocnemius, of residents throughout the annual cycle when compared to migrants. Pectoralis aromatase expression was higher in resident males compared to migrant males. No differences were observed for 5α-reductase 2. Between these two subspecies, patterns of plasma testosterone and androgen receptors appear to be conserved, however estrogen receptor gene expression appears to have diverged.

Stereotactic radiosurgery for melanoma brain metastases: Concurrent immune checkpoint inhibitor therapy associated with superior clinicoradiological response outcomes.

INTRODUCTION/PURPOSE: This study assessed long-term clinical and radiological outcomes following treatment with combination stereotactic radiosurgery (SRS) and immunotherapy (IT) for melanoma brain metastases (BM). METHODS: A retrospective review was performed in a contemporary cohort of patients with melanoma BM at a single tertiary institution receiving Gamma Knife® SRS for melanoma BM. Multivariate Cox proportional-hazards modelling was performed with a P <0.05 for significance. RESULTS: 101 patients (435 melanoma BM) were treated with SRS between January-2015 and June-2019. 68.3% of patients received IT within 4 weeks of SRS (concurrent) and 31.7% received SRS alone or non-concurrently with IT. Overall, BM local control rate was 87.1% after SRS. Median progression free survival was 8.7 months. Median follow-up was 29.2 months. On multivariate analysis (MVA), patients receiving concurrent SRS-IT maintained a higher chance of achieving a complete (CR) or partial response (PR) [HR 2.6 (95% CI: 1.2-5.5, P = 0.012)] and a reduced likelihood of progression of disease (PD) [HR 0.52 (95% CI: 0.16-0.60), P = 0.048]. Any increase in BM volume on the initial MRI 3 months after SRS predicted a lower likelihood of achieving long-term CR or PR on MVA accounting for concurrent IT, BRAF status and dexamethasone use [HR = 0.048 (95% CI: 0.007-0.345, P = 0.0026)]. Stratified volumetric change demonstrated a sequential relationship with outcomes on Kaplan-Meier analysis. CONCLUSION: Concurrent SRS-IT has favourable clinical and radiological outcomes with respect to CR, PR and a reduced likelihood of PD. Changes in BM volume on the initial MRI 3 months after SRS were predictive of long-term outcomes for treatment response.

Treatment of primary hyperparathyroidism in a Miniature Horse using chemical ablation of abnormal parathyroid tissue localized by 3-phase computed tomography.

A 15-year-old Miniature Horse mare with persistently increased plasma calcium (total and ionized) and serum parathyroid hormone concentrations was presented for suspected primary hyperparathyroidism. Ultrasonography of the thyroid region identified an enlarged heterogeneous mass axial to the right thyroid lobe suggestive of an enlarged parathyroid gland, which was further confirmed using sestamibi nuclear scintigraphy and 3-phase computed tomography. Percutaneous ultrasound-guided ethanol ablation of the mass, a method not previously described in the horse, was performed under general anesthesia resulting in rapid normalization of plasma ionized calcium and serum parathyroid hormone concentrations. Ablation of abnormal parathyroid gland tissue may be a suitable alternative to surgical resection in certain cases of primary hyperparathyroidism in the horse.

You are what you eat: How and when workplace healthy eating cultivates coworker perceptions and behaviors.

Food consumption has been conceptualized as an integral aspect of employee well-being. Whereas most research in the organizational literature to date is motivated by individual health outcomes, we assert that eating at work also entails interpersonal implications. In this manuscript, we draw from consumption stereotype theory and suggest that workplace healthy eating affects how employees are perceived and treated at work. Specifically, we posit that workplace healthy eating influences the extent to which a focal employee is attributed the trait of self-control, which subsequently impacts coworker citizenship behavior and social undermining enacted toward the focal employee. Moreover, we postulate healthy eating climate as a boundary condition to the effects of workplace healthy eating-when there is a salient healthy eating climate, workplace healthy eating is a weaker signal in the trait attribution process. Overall, we extend the concept of employee eating to the interpersonal level by explaining how employee eating directly affects coworker interactions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A sleep and self-control model of cyber incivility at work.

OBJECTIVES: To conduct an empirical test of a conceptual model in which sleep duration would have an indirect negative effect on cyber incivility at work, mediated by self-regulatory fatigue and moderated by agreeableness. DESIGN: A 2-week daily diary study in which employees completed daily surveys in the mornings and at the end of the workday. SETTING: An observational study which measured sleep and work behaviors in the daily work lives of our participants. PARTICIPANTS: One hundred thirty-one adults who were full-time employees and were also enrolled in a 2-year Executive Post Graduate Program at a university in India. MEASUREMENT: Participants completed a baseline survey which included agreeableness as well as demographics and person-level control variables. At 7 AM each workday, we sent participants the morning survey which included the sleep measure. At 4 PM each workday, we sent participant the end of workday survey which included measures of self-regulatory fatigue, cyber incivility, and day-level control variables. Participants completed a total of 945 morning surveys and 843 afternoon surveys. RESULTS: Results supported our model. Sleep duration was negatively associated with self-regulatory fatigue, which was positively related to cyber incivility. Agreeableness moderated the relationship between sleep duration and self-regulatory fatigue, as well as the indirect effect of sleep duration on cyber incivility. CONCLUSION: Employees have more self-regulatory fatigue and thus engage in higher levels of cyber incivility at work after a shorter night of sleep, especially if those employees are low in agreeableness.

Enrollment Challenges: Recruiting Children From Diverse Racial and Ethnic Communities to a Study of Physical Activity and Perceived Stress.

INTRODUCTION: Effective recruitment and retention can be particularly difficult when research involves children from diverse backgrounds. The purpose of this article is to describe productive methods for recruiting children from diverse racial and ethnic communities. A better understanding of this process will help researchers improve recruitment efforts and better address health disparities. METHOD: Using data retrieved from a cross-sectional study examining children's physical activity and stress, strategies and efforts for recruitment and retention were recognized and identified. RESULTS: During a 5-month recruitment period, 92 potential participants contacted research staff after multiple strategies were executed. Among them, 83.7% were successfully recruited, and 93.5% completed the study; additionally, 54% were White and about 30% Hispanic. Although initial recruitment plans were school based, the majority were recruited by referrals from current participants. DISCUSSION: Productive strategies varied by race, ethnic, and cultural backgrounds. Proactive strategies and limitations, such as the use of a smartphone or Quick Response code, are discussed.

An exploration of employee dreams: The dream-based overnight carryover of emotional experiences at work.

OBJECTIVE: We sought to explore the manner in which daily challenge and hindrance stressors at work may be associated with mood the next day, through the mediating mechanisms of presleep rumination and moods experienced while asleep during dreams. METHODS: A daily diary study in which 94 adults with full-time jobs completed 2 surveys per day for 2 work weeks. Each morning, participants reported the degree to which they engaged in rumination before sleep the previous night, the affective tone of their dreams, and their mood at that moment. Each evening participants reported their experiences of challenge and hindrance stressors at work that day. RESULTS: Hindrance stressors were positively related to next-morning negative affect via the effects of rumination and negative affect in dreams. Challenge stressors negatively related to positive affect in the morning, via rumination and lowered positive affect in dreams. These results occurred above and beyond the effects of sleep quantity, sleep quality, and several other time-based control variables. CONCLUSIONS: Dreams play an important role in how work stressors which are experienced in a given workday are associated with mood the next morning.

Stereotactic radiotherapy for large vestibular schwannomas: Volume change following single fraction versus hypofractionated approaches.

Hypofractionated stereotactic radiotherapy is a treatment option for large vestibular schwannomas supported by an increasing evidence. A single institution retrospective review of large (>3.5cc) vestibular schwannomas treated with hypofractionated stereotactic radiotherapy and single-session radiosurgery was conducted. Using serial follow up scans, a volumetric analysis of tumor volume change over time was performed. Vestibular schwannomas treated with hypofractionated stereotactic radiotherapy appeared to reduce in volume significantly faster than those treated with single-session radiosurgery. Cystic lesions reduced in volume faster than solid lesions. There was no significant difference in the rates of radiological and symptomatic oedema, nor subsequent dexamethasone requirement between the two treatment modalities.

Developmental anomalies of the lateral portion of the cervical neural arch: Multimodal imaging and clinical implications.

OBJECTIVE: This study aimed to describe the imaging spectrum of developmental anomalies of the lateral portion of the cervical neural arch. METHOD: This was a five-year retrospective review of consecutive computed tomography (CT) scans of the cervical spine for structural anomalies of the cervical vertebral pedicle and facets. CT, radiographs and, when available, magnetic resonance imaging studies were independently reviewed. Anomalies were grouped into the following three categories: the absence of a pedicle, clefts in the vertebral arch or isolated dysmorphism of the facet. Clinical data on demographics and neurological outcomes were documented. RESULTS: Among 9134 consecutive patients undergoing a CT scan of the cervical spine, 18 (0.2%) patients were found to have developmental anomalies of the pedicle and facets. Findings included 7/18 (39%) with congenital absence of a pedicle, 8/18 (44%) with clefts in the vertebral arch and 3/18 (17%) with isolated dysmorphism of the articular facets. No acute neurological deficits or spinal cord injuries were reported. Associated chronic symptoms included neck pain 10/18 (56%), radiculopathy 7/18 (39%) and myelopathy 1/18 (6%). CONCLUSION: Developmental anomalies of the pedicle and facet may mimic traumatic spinal pathologies. Recognising a diverse spectrum of imaging findings is vital to prevent misdiagnosis and unnecessary intervention.

Evidence of dose-response following hypofractionated stereotactic radiotherapy to the cavity after surgery for brain metastases.

BACKGROUND AND OBJECTIVE: A retrospective review of consecutive patients between January 2012 and December 2018 receiving hypofractionated stereotactic radiotherapy (HSRT) to the cavity after resection for brain metastases was performed. METHODS: Treatment was delivered using an appropriately commissioned linear accelerator. The primary outcome was time to radiological or histological confirmation of local recurrence following completion of HSRT. Dose-fractionation regimens were converted to biologically 2 Gy-equivalent doses assuming α/ß = 10 (EQD2[10]). Multivariate Cox proportional hazards modelling was performed to determine hazard ratios (HR) with respective 95% confidence intervals (CI). The Log-rank test was used to determine p values taking statistical significance p < 0.05. RESULTS: There were 134 patients and 144 cavities identified. The most common primary histologies were melanoma (n = 49) and lung (n = 32). 116 patients (87%) underwent a gross total resection. Median planning target volume (PTV) was 28 cm3 (range 2.4-149.2). Median EQD2[10] was 38.4 Gy (range 22.3-59.7) and 24 Gy in 3 fractions was the most common regimen. 12 (9%) patients demonstrated local recurrence at median interval 215 days (range 4-594). 7 (5%) patients experienced grade 3 or higher toxicities. In multivariate analysis, EQD2[10] was associated with local failure such that increased equivalent doses improved local control [HR = 0.79 and 95% CI 0.65-0.96, p = 0.0192]. There were no significant associations for primary histology, patient age, volume of residual disease, PTV volume or location. CONCLUSION: This large series demonstrates that HSFRT to the surgical resection cavity for brain metastases has improved local control with increasing dose. Rates of grade 3 or higher toxicity were low overall.

Iodine-stained fragmented thromboembolism.

AIM: Iodine-stained fragmented thromboembolism (ISFT) is a rare phenomenon encountered in the immediate aftermath of mechanical thrombectomy or rarely as a complication of post-carotid stenting. The aim was to describe the imaging appearance and discuss its pathophysiology. METHOD: This is a retrospective review of patients who underwent mechanical thrombectomy for acute stroke at a single institution over the period of one year. All patients underwent the standard acute stroke imaging protocol (CT head, CT angiogram (CTA) and CT brain perfusion) and when clinically appropriate followed by catheter angiogram and mechanical thrombectomy. ISFT was defined as an arterial luminal filling defect with Hounsfield density equal to or greater than iodine seen on the biplanar CT or conventional CT. The presence and location of ISFT were documented. Standard CT angiogram (CTA) or magnetic resonance angiogram (MRA) was performed 24-48 hours after the neurointerventional procedure to assess for recanalization, volume of infarction and the fate of the ISFT. RESULTS: ISFTs were identified in eight (five males and three females, age range 18-80 years) out of 49 patients in the following locations: distal M1 (n = 1), M2 (n = 4), M3 (n = 1), A1 (n = 1), distal A2 (n = 1). ISFT and vessel recanalization occurred in five patients on follow-up. ISFT and vessel occlusion persisted in two patients. CONCLUSION: ISFT is likely the result of mechanical disruption of a thromboembolus, and porosity of the thromboembolus fragment may transiently retain iodinated contrast. Recognition of this entity may be important to aid detection of residual thromboembolism and avoid misinterpretation as calcified thromboembolism.

Massive subcutaneous emphysema mimicking anaphylaxis - pathological and radiological correlations.

This report details the pathological and radiological findings in a rare case of massive subcutaneous emphysema. A 74-year-old male presented with sudden onset dyspnea and facial swelling following a fall. His symptoms were refractory to treatments for anaphylaxis, which was suspected clinically, and he quickly succumbed. Autopsy, including post mortem CT scan revealed the underlying etiology to be multiple rib fractures with rupture of the parietal pleura, bilateral pneumothoraxes and massive subcutaneous emphysema involving the face, torso and upper limbs. Multiple frothy air bubbles were observed throughout the mediastinal adipose tissues on internal examination. Our findings echo those of rare previous reports and show how subcutaneous emphysema may, in rare circumstances, mimic anaphylaxis.

(Pro)renin receptor knockdown in the paraventricular nucleus of the hypothalamus attenuates hypertension development and AT1 receptor-mediated calcium events.

Activation of the brain renin-angiotensin system (RAS) is a pivotal step in the pathogenesis of hypertension. The paraventricular nucleus (PVN) of the hypothalamus is a critical part of the angiotensinergic sympatho-excitatory neuronal network involved in neural control of blood pressure and hypertension. However, the importance of the PVN (pro)renin receptor (PVN-PRR)-a key component of the brain RAS-in hypertension development has not been examined. In this study, we investigated the involvement and mechanisms of the PVN-PRR in DOCA-salt-induced hypertension, a mouse model of hypertension. Using nanoinjection of adeno-associated virus-mediated Cre recombinase expression to knock down the PRR specifically in the PVN, we report here that PVN-PRR knockdown attenuated the enhanced blood pressure and sympathetic tone associated with hypertension. Mechanistically, we found that PVN-PRR knockdown was associated with reduced activation of ERK (extracellular signal-regulated kinase)-1/2 in the PVN and rostral ventrolateral medulla during hypertension. In addition, using the genetically encoded Ca2+ biosensor GCaMP6 to monitor Ca2+-signaling events in the neurons of PVN brain slices, we identified a reduction in angiotensin II type 1 receptor-mediated Ca2+ activity as part of the mechanism by which PVN-PRR knockdown attenuates hypertension. Our study demonstrates an essential role of the PRR in PVN neurons in hypertension through regulation of ERK1/2 activation and angiotensin II type 1 receptor-mediated Ca2+ activity. NEW & NOTEWORTHY PRR knockdown in PVN neurons attenuates the development of DOCA-salt hypertension and autonomic dysfunction through a decrease in ERK1/2 activation in the PVN and RVLM during hypertension. In addition, PRR knockdown reduced AT1aR expression and AT1R-mediated calcium activity during hypertension. Furthermore, we characterized the neuronal targeting specificity of AAV serotype 2 in the mouse PVN and validated the advantages of the genetically encoded calcium biosensor GCaMP6 in visualizing neuronal calcium activity in the PVN.

From Pleistocene to Holocene: the prehistory of southwest Asia in evolutionary context.

In this paper I seek to show how cultural niche construction theory offers the potential to extend the human evolutionary story beyond the Pleistocene, through the Neolithic, towards the kind of very large-scale societies in which we live today. The study of the human past has been compartmentalised, each compartment using different analytical vocabularies, so that their accounts are written in mutually incompatible languages. In recent years social, cognitive and cultural evolutionary theories, building on a growing body of archaeological evidence, have made substantial sense of the social and cultural evolution of the genus Homo. However, specialists in this field of studies have found it difficult to extend their kind of analysis into the Holocene human world. Within southwest Asia the three or four millennia of the Neolithic period at the beginning of the Holocene represents a pivotal point, which saw the transformation of human society in the emergence of the first large-scale, permanent communities, the domestication of plants and animals, and the establishment of effective farming economies. Following the Neolithic, the pace of human social, economic and cultural evolution continued to increase. By 5000 years ago, in parts of southwest Asia and northeast Africa there were very large-scale urban societies, and the first large-scale states (kingdoms). An extension of cultural niche construction theory enables us to extend the evolutionary narrative of the Pleistocene into the Holocene, opening the way to developing a single, long-term, evolutionary account of human history.