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ABSTRACT:Geographic, social, political, and economic factors shape access to advanced neurotechnologies, yet little previous research has explored the barriers, enablers, and areas of opportunity for equitable and meaningful access for diverse patient communities across Canada. We applied a mixed-mode approach involving semi-structured interviews and rating scale questions to consult with 24 medical experts who are involved in the care of patients who undergo functional neurosurgery targeting the brain. Seven major themes emerged from the qualitative analysis: Health care system, Neurotechnology features, Patient demographics, Target condition features, Ethics, Upstream barriers and enablers, and Areas of opportunity. Descriptive statistics of the Likert-scale responses suggest that interviewees perceive a disparity between the imperative of access to advanced neurotechnologies for people living in rural and remote areas and the likelihood of achieving such access. The results depict a complex picture of access to functional neurosurgery in Canada with pockets of excellence and a motivation to improve the availability of care for vulnerable populations through the expansion of distributed care models, improved health care system efficiencies, increasing funding and support for patient travel, and increasing awareness about and advocacy for advanced neurotechnologies.

Electroencephalographic monitoring provides critical diagnostic and management information about patients with epilepsy and seizure mimics. Admission to an epilepsy monitoring unit (EMU) is the gold standard for such monitoring in major medical facilities worldwide. In many countries, access can be challenged by limited resources compared to need. Today, triaging admission to such units is generally approached by unwritten protocols that vary by institution. In the absence of explicit guidance, decisions can be ethically taxing and are easy to challenge. In an effort to address this gap, we propose a two-component approach to EMU triage that takes into account the unique landscape of epilepsy monitoring informed by triage literature from other areas of medicine. Through the strategic component, we focus on the EMU wait list management infrastructure at the institutional level. Through the principled component, we apply a combination of the ethical principles of prioritarianism, utilitarianism and justice to triage; and we use individual case examples to illustrate how they apply. The effective implementation of this approach to specific epilepsy centres will need to be customised to the nuances of different settings, including diverse practice patterns, patient populations and constraints on resource distribution, but the conceptual consolidation of its components can alleviate some of the pressures imposed by the complex decisions involved in EMU triage.

ABSTRACT:Background:Novel neurointerventions present innovative therapeutic approaches to a range of treatment-refractory disorders. We sought to characterize factors that inform and define translational readiness for first-in-human (FIH) neuromodulatory trials.Methods:We used a two-part methodology involving a scoping review of the biomedical literature on the readiness of FIH trials for both neurological and non-neurological applications, and semi-structured interviews with stakeholders about decision-making for neuromodulation using magnetic resonance-guided focused ultrasound as a case example.Results:One hundred and thirty factors relevant to FIH readiness were identified in the scoping review. Trial design, adequacy of preclinical evidence, and riskwere ubiquitous across biotechnologies. Target organ, target function, and inadequacy of animal modelswere dominant in the neurointervention literature. Interview results on the relative importance of these factors reveal divergent values, priorities, and understandings both between patients and clinicians and between patients affected by different conditions.Conclusion:Readiness of neurotechnology for FIH trials is defined by a multitude of interacting factors that pertain to clinical and nonclinical priorities, perceptions, and values.

Factorial Survey Analysis (FSA) is an analytical tool that presents respondents with fictional situations (“vignettes”) to be rated or judged. In this paper we study the use of FSA in labour market sociology, with a particular focus on employer-based surveys, and what they can teach us about hiring preferences. FSA is useful in this context as it targets employers directly and comes close to a causal design. This review article seeks to pinpoint the contributions FSA has made to the field, identify its limits and propose topics in which it may be useful.

Leukotriene B4(LTB4) plays a prominent role in innate immunity as it induces phagocyte recruitment, the release of antimicrobial effectors, and as it potentiates the ingestion and killing of pathogens. In humans, LTB4has a short half‐life and is rapidly metabolized by leukocytes, notably into 20‐OH‐ and 20‐COOH‐LTB4by neutrophils. Although these LTB4metabolites bind to the BLT1receptor with high affinity, they activate neutrophils to a much lower extent than LTB4. We thus postulated that LTB4metabolites could dampen BLT1‐mediated responses, therefore limiting the impact of LTB4on human neutrophil functions. We found that 20‐OH‐LTB4and 20‐COOH‐LTB4inhibited all of the LTB4‐mediated neutrophil responses we tested (migration, degranulation, leukotriene biosynthesis). The potencies of the different compounds at inhibiting LTB4‐mediated responses were 20‐OH‐LTB4= CP 105,696 (BLT1antagonist) > > 20‐COOH‐LTB4≥ resolvin E1(RVE1). In contrast, the fMLP‐ and IL‐8‐mediated responses we tested were not affected by the LTB4metabolites or RVE1. 20‐OH‐LTB4and 20‐COOH‐LTB4also inhibited the LTB4‐mediated migration of human eosinophils but not that induced by 5‐KETE. Moreover, using 20‐COOH‐LTB4, LTB4, and LTB4‐alkyne, we show that LTB4is a chemotactic, rather than a chemokinetic factor for both human neutrophils and eosinophils. In conclusion, our data indicate that LTB4metabolites and RVE1act as natural inhibitors of LTB4‐mediated responses. Thus, preventing LTB4ω‐oxidation might result in increased innate immunity and granulocyte functions. The rapid metabolism of LTB4into 20‐OH‐LTB4leads to less active BLT1 ligands that inhibit further responses to LTB4.

Advances in perinatal care in the developed world have resulted in more children living into adulthood with complex chronic health conditions. Transition is a process to improve and maximize the functional status of adolescents via the provision of adequate and appropriate health services in adulthood. This process is frequently disjointed, fragmented and inconsistent and inadequate transition increases morbidity, hospital admissions and urgent interventions. Ten thousand children are diagnosed with hydrocephalus annually in North America. Most survive to adulthood yet there are few transitioning programs and little research data on successful programs for this population.

Two experiments investigated the effects of the number of health recommendations (e.g., quit smoking; relax for a day) contained in a health-promotion message on recommendation recall and intentions to enact the recommendations. We hypothesized that if recommendations are stored individually, a higher number of presented recommendations will increase the number of recalled recommendations. As the number of recommendations increases, however, recipients are likely to summarize more recommendations as part of a single, more general theme (or header), resulting in a decrease in the proportion of recalled recommendations. Two experiments (N= 193 and N= 266) found that the total number of recalled recommendations increased and the proportion of recalled recommendations decreased with the number of presented recommendations. Experiment 2 replicated the findings with the number and the proportion of intended behaviors. The implications of these findings for future behavioral health interventions are discussed.

Blunt cerebrovascular injury is an important cause of morbidity and mortality following head trauma. Intracranial vessel dissections, carotid-cavernous fistulae, and pseudo-aneurysms are uncommon traumatic vascular lesions with limited evidence to guide endovascular management.

Therapeutic strategies based on MEK inhibition may require complementation of ERK inhibition in chronic inflammatory conditions featuring a strong neutrophilic component. Neutrophils influence innate and adaptative immunity, notably through the generation of numerous cytokines and chemokines and through the modulation of their constitutive apoptosis. Several signaling cascades are known to control neutrophil responses, including the MEK pathway, which is normally coupled to ERK. However, we show here that in human neutrophils stimulated with cytokines or TLR ligands, MEK and ERK are activated independently of each other. Pharmacological blockade of MEK had no effect on the induction of ERK kinase activity and vice versa. In autologous PBMC exposed to the same stimuli or in neutrophils exposed to chemoattractants, this uncoupling of MEK and ERK was not observed. Whereas we had shown before that MEK inhibition impairs cytokine generation translationally in LPS‐ or TNF‐stimulated neutrophils, ERK inhibition affected this response transcriptionally and translationally. Transcriptional targets or ERK include the mitogen‐ and stress‐activated protein kinase 1 (MSK‐1) and its substrates, C/EBPβ and CREB, whereas translational targets include the S6 kinase and its substrate, the S6 ribosomal protein. In addition to affecting cytokine production, ERK inhibition interfered with how LPS or TNF promotes neutrophil survival and levels of the myeloid cell leukemia 1 (Mcl‐1) antiapoptotic protein. Whereas the ERK‐activating kinase was not identified, we found that the MAP3K, TGF‐β‐activated kinase 1 (TAK1), acts upstream of ERK and MEK in neutrophils. Our results document a functional uncoupling of the MEK/ERK module under certain stimulatory conditions and suggest that therapeutic strategies based on MEK inhibition might benefit from being complemented by ERK inhibition, particularly in chronic inflammatory conditions featuring a strong neutrophilic component.

AbstractThis paper blends recent research on hierarchy and democratization to examine the theoretical and empirical costs of treating regime type exogenously in the literature most identified with studying its impact on international politics. It argues that the apparent peace among democratic states that emerges in the aftermath of World War I is not caused by domestic institutional attributes normally associated with democracy. Instead, this peace is an artifact of historically specific great power settlements. These settlements shape subsequent aggregate patterns of military conflict by altering the organizational configuration of the system in three critical ways—by creating new states, by altering hierarchical orders, and by influencing regime type in states. These claims are defended with a series of tests that show first how the statistical relationship between democracy and peace has exhibited substantial variation across great power orders; second, that this statistical relationship breaks down with theoretically motivated research design changes; and third, that great powers foster peace and similar regime types within their hierarchical orders. In short, the relationship between democracy and peace is spurious. The international political order is still built and managed by great powers.

Cytokine production and delayed apoptosis are influenced by the TAK1‐p38‐MNK1 axis in neutrophils, which also affects molecules implicated in translation initiation control. A growing number of inflammatory and immune processes in vivo have been shown to be influenced by neutrophil‐derived cytokines. Whereas the underlying transcriptional mechanisms are increasingly well understood, the translational regulation of this neutrophil response remains largely unexplored. Here, we show that the MNK1, which participates in translational control in several cell types, is activated in response to physiological neutrophil agonists (LPS, TNF‐α) in the cytoplasmic and nuclear compartments. With the use of various pharmacological inhibitors, we found that MNK1 activation takes place downstream of the TAK1‐p38 MAPK axis in neutrophils, whereas the MEK/ERK, JNK, PI3K, and PKC pathways are not involved. Pharmacological blockade of MNK1, as well as overexpression experiments, established that cytokine protein synthesis (but not gene expression) is under the control of MNK1 in neutrophils. Likewise, MNK1 inhibition reversed the antiapoptotic effect of LPS and TNF‐α in neutrophils, and this was accompanied by a decreased expression of the antiapoptotic protein Mcl‐1. Thus, MNK1 appears to be an important regulator of neutrophil responses. Although MNK1 inhibition did not affect protein recruitment to mRNA caps, it decreased the phosphorylation of molecules implicated in translation initiation control, such as S6K, S6, and hyperphosphorylated 4E‐BP1. These molecular targets of MNK1 are shared with those of PI3K in neutrophils, and accordingly, MNK1 inhibition partially impaired the belated PI3K/Akt activation elicited by LPS or TNF in these cells. Given the importance of neutrophils and their products in numerous chronic inflammatory disorders, MNK1 could represent an attractive therapeutic target.

Evaluation of wildlife-habitat relationships at the landscape level provides insight into how habitat connectivity, fragmentation and land-use changes may affect wildlife populations. Although previous studies have demonstrated that habitat composition and configuration at large scales may affect the presence, survival and movement of carnivore species, no such analyses have been conducted for the gray fox Urocyon cinereoargenteus. We used a generalized correlative mapping approach to investigate the relationship of gray fox relative abundance to landscape variables at the county scale in Illinois, USA. Relative abundance of gray foxes was high in 37 of 102 (36%) counties. Four models were competitive based on ?AICcscores, and these models indicated that standard deviation of the perimeter-area ratio of agricultural patches, interspersion and juxtaposition index of grassland patches, coefficent of variation of the proximity index of forest patches and relative patch richness of the landscape affected gray fox relative abundance. The variables occurring in our competing models indicate that the relative abundance of the gray fox is higher in counties containing a high level of fragmentation of preferred habitat types (i.e. forests and grasslands) and lower dispersion of less preferred habitat types (i.e. agriculture). Our results reflect gray fox habitat use at smaller scales, and at the landscape scale, gray fox abundance is influenced by how cover-type patches are configured.

The major histocompatability complex on chromosome 6p has often been identified as containing potential risk factors for schizophrenia. The NOTCH4gene is located within this region (6p21.3) and sequence variants have previously shown association to the disease. It is further implicated from a functional standpoint as it plays a critical role during the neurodevelopmental process.

Sepsis is exceedingly burdensome for hospital intensive care unit caregivers, and its incidence, as well as sepsis-related deaths, is increasing steadily. Sepsis is characterized by a robust increase in NO production throughout the organism that is driven by iNOS. Moreover, NO is an important factor in the development of septic shock and is synthesized by NOS, an enzyme expressed by a variety of cells, including vascular endothelium, macrophages, and neutrophils. However, the effects of NO on leukocyte functions, and the underlying mechanisms, are relatively unknown. Thus, the present review focuses on the effects of NO and its derivatives on cells of the immune system. Experimental evidences discussed herein show that NO induces posttranslational modifications of key proteins in targeted processes with the potential of deterring cellular physiology. Consequently, the manipulation of NO distribution in septic patients, used in conjunction with conventional treatments aimed at restoring normal immune functions, may represent a valuable therapeutic strategy.

Let Wnbe a simple Markov chain on the integers. Suppose that Xnis a simple Markov chain on the integers whose transition probabilities coincide with those of Wnoff a finite set. We prove that there is an M> 0 such that the Markov chain Wnand the joint distributions of the first hitting time and first hitting place of Xnstarted at the origin for the sets {-M, M} and {-(M+ 1), (M+ 1)} algorithmically determine the transition probabilities of Xn.

Despite substantial evidence that international trade has promoted peace in the post–World War II era, the commercial peace research program still faces an important historical challenge. Dramatic economic integration in the nineteenth century failed to prevent the increasing interstate hostilities that culminated in the outbreak of war in 1914. This article uses a theoretical revision grounded in standard trade theory to reexamine the relationship between commerce and peace in the fifty years before World War I, a period often referred to as the first era of globalization. The article focuses on domestic conflict over commercial policy rather than on interdependence to understand the conditions under which globalization promotes peace. In a sample dating from 1865 to 1914, the authors find that lower regulatory barriers to commerce reduce participation in militarized interstate disputes. Contradicting conventional wisdom, this evidence affirms a basic premise of commercial liberalism during the first era of globalization—free trade promotes peace.

Despite substantial evidence that international trade has promoted peace in the post—World War II era, the commercial peace research program still faces an important historical challenge. Dramatic economic integration in the nineteenth century failed to prevent the increasing interstate hostilities that culminated in the outbreak of war in 1914. This article uses a theoretical revision grounded in standard trade theory to reexamine the relationship between commerce and peace in the fifty years before World War I, a period often referred to as the first era of globalization. The article focuses on domestic conflict over commercial policy rather than on interdependence to understand the conditions under which globalization promotes peace. In a sample dating from 1865 to 1914, the authors find that lower regulatory barriers to commerce reduce participation in militarized interstate disputes. Contradicting conventional wisdom, this evidence affirms a basic premise of commercial liberalism during the first era of globalization—free trade promotes peace.

The ability of human neutrophils to express a variety of genes encoding inflammatory mediators is well documented, and mounting evidence suggests that neutrophil‐derived cytokines and chemokines contribute to the recruitment of discrete leukocyte populations at inflammatory sites. Despite this, our understanding of the signaling intermediates governing the generation of inflammatory cytokines by neutrophils remains fragmentary. Here, we report that inhibitors of the p38 MAPK and MEK pathways substantially diminish the release of (and in the case of p38 inhibitors, the gene expression of) several inflammatory cytokines in neutrophils stimulated with LPS or TNF. In addition, various NF‐κB inhibitors were found to profoundly impede the inducible gene expression and release of inflammatory cytokines in these cells. The MAPK inhibitors did not affect NF‐κB activation; instead, the transcriptional effects of the p38 MAPK inhibitor appear to involve transcriptional factor IID. Conversely, the NF‐κB inhibitors failed to affect the activation of MAPKs. Finally, the MAPK inhibitors were found to prevent the activation a key component of the translational machinery, S6 ribosomal protein, in keeping with their post‐transcriptional impact on cytokine generation. To our knowledge, this constitutes the first demonstration that in neutrophils, the inducible expression of proinflammatory cytokines by physiological stimuli largely reflects the ability of the latter to activate NF‐κB and selected MAPK pathways. Our data also raise the possibility that NF‐κB or MAPK inhibitors could be useful in the treatment of inflammatory disorders in which neutrophils predominate.

We analyze the SDSS Lya forest PF(k, z) measurement to determine the linear theory power spectrum. Our analysis is based on fully hydrodynamic simulations, extended using hydro-particle-mesh simulations. We account for the effect of absorbers with damping wings, which leads to an increase in the slope of the linear power spectrum. We break the degeneracy between the mean level of absorption and the linear power spectrum without significant use of external constraints. We infer linear theory power spectrum amplitude Dimg1.gif(kp = 0.009 s km-1, zp = 3.0) = 0.452img2.gifimg3.gif and slope neff(kp, zp) = -2.321img4.gifimg5.gif (possible systematic errors are included through nuisance parameters in the fit: a factor [?]5 smaller errors would be obtained on both parameters if we ignored modeling uncertainties). The errors are correlated and not perfectly Gaussian, so we provide a kh2 table to accurately describe the results. The result corresponds to s8 = 0.85, n = 0.94 for a LCDM model with Om = 0.3, Ob = 0.04, and h = 0.7 but is most useful in a combined fit with the CMB. The inferred curvature of the linear power spectrum and the evolution of its amplitude and slope with redshift are consistent with expectations for LCDM models, with the evolution of the slope, in particular, being tightly constrained. We use this information to constrain systematic contamination, e.g., fluctuations in the UV background. This paper should serve as a starting point for more work to refine the analysis, including technical improvements such as increasing the size and number of the hydrodynamic simulations and improvements in the treatment of the various forms of feedback from galaxies and quasars.

The transverse proximity effect is the expected decrease in the strength of the Lya forest absorption in a QSO spectrum when another QSO lying close to the line of sight enhances the photoionization rate above that due to the average cosmic ionizing background. We select three QSOs from the Early Data Release of the Sloan Digital Sky Survey that have nearby foreground QSOs, with proper line-of-sight tangential separations of 0.50, 0.82, and 1.10 h-1 Mpc. We estimate that the ionizing flux from the foreground QSO should increase the photoionization rate by a factor (94, 13, 13) in these three cases, which would be clearly detectable in the first QSO and marginally so in the other two. We do not detect the transverse proximity effect. Three possible explanations are provided: an increase of the gas density in the vicinity of QSOs, time variability, and anisotropy of the QSO emission. We find that the increase of gas density near QSOs can be important if they are located in the most massive halos present at high redshift, but it is not enough to fully explain the absence of the transverse proximity effect. Anisotropy requires an unrealistically small opening angle of the QSO emission. Variability demands that the luminosity of the QSO with the largest predicted effect was much lower 106 yr ago, whereas the transverse proximity effect observed in the He II Lya absorption in QSO 0302-003 by Jakobsen et al. implies a lifetime longer than 107 yr. A combination of all three effects may better explain the lack of Lya absorption reduction. A larger sample of QSO pairs may be used to diagnose the environment, anisotropy, and lifetime distribution of QSOs.

The correlation between Lya absorption in the spectra of quasar pairs can be used to measure the transverse distance scale at z ~ 2, which is sensitive to the cosmological constant (OL) or other forms of vacuum energy. Using hydro-PM simulations, I compute the three-dimensional power spectrum of the Lya forest flux, PF(img1.gif), from which the redshift-space anisotropy of the correlation can be obtained. I compute directly the linear theory bias parameters of the Lya forest, potentially allowing simulation results to be extended to arbitrarily large scales. I investigate the dependence of PF(img1.gif) on the primordial power spectrum, the temperature-density relation of the gas, and the mean flux decrement, finding that the redshift-space anisotropy is relatively insensitive to these parameters. A table of results is provided for different parameter variations. I investigate the constraint that can be obtained on OL using quasars from a large survey. Assuming 13 img2.gif2 pairs at a separation of less than th and including separations less than 10', a measurement to [?] 5% can be made if simulations can predict the redshift-space anisotropy with [?] 5% accuracy or to [?] 10% if the anisotropy must be measured from the data. The Sloan Digital Sky Survey (SDSS) will obtain spectra for a factor of ~5 fewer pairs than this, so follow-up observations of fainter pair candidates will be necessary. I discuss the requirements on the spectral resolution and signal-to-noise ratio (SDSS quality spectra are sufficient). I find that a box size of ~40 h-1 Mpc and a resolution of ~40 h-1 kpc are necessary for convergence of the calculations to [?] 5% on all relevant scales, although somewhat poorer resolution can be used for large scales.

We present predictions of the correlation between the Lya forest absorption in quasar spectra and the mass within ~5 h-1 Mpc (comoving) of the line of sight, using fully hydrodynamic and hydro-PM numerical simulations of the cold dark matter model supported by present observations. The observed correlation based on galaxies and the Lya forest can be directly compared to our theoretical results, assuming that galaxies are linearly biased on large scales. Specifically, we predict the average value of the mass fluctuation, [?]dm[?], conditioned to a fixed value of the Lya forest transmitted flux, dF, after they have been smoothed over a 10 h-1 Mpc cube and line-of-sight interval, respectively. We find that the relation between dF/sF and [?]dm[?]/sm (where sm and sF are the rms dispersions) has a predicted slope of ~0.6 at dF = 0 that is largely insensitive to the cosmological model and other Lya forest parameters. Comparison of our predictions to observations should provide a fundamental test of our ideas on the nature of the Lya forest and the distribution of galaxies and can yield a measurement of the bias factor of any type of galaxy that is observed in the vicinity of Lya forest lines of sight.

The convertase furin is involved in the maturation of key growth/aggregation mediators synthesized by the platelet producers, megakaryocytes, but the regulation of furin in these cells remains unknown. Computer-assisted search of the furin promoter sequence revealed multiple potential binding motifs for GATA-1, suggesting that furin is expressed and regulated in these cells. Using megakaryoblastic Dami cells, we observed that fur mRNA expression increased gradually on phorbol 12-myristate 13-acetate–induced differentiation, reaching maximum levels (8.3-fold increase) at 10 days. Transient transfections with P1, P1A, or P1B fur-LUC–promoter constructs revealed that in Dami cells, the P1 promoter is the strongest and the most sensitive to forced expression of GATA-1. Coexpression of GATA-1 and its comodulator, Friend of GATA-1 (FOG-1), resulted in a cooperative increase in P1 activity. Deletion analysis indicated that important GATA-1–regulated sequences are located in the most proximal region of the P1 promoter. Further analysis revealed 2 potential GATA-binding motifs at positions −66 and +62. Point mutation of each of the 2 motifs indicated that the intactness of the first GATA site is required for full basal and GATA-1–stimulated promoter activity. Finally, the inhibition of furin activity through gene transfer of the inhibitor α1-AT-PDX led to a block in maturation of the furin substrates transforming growth factor-β1 and platelet-derived growth factor. Taken together, these results indicate that the most proximal GATA element in the P1 promoter is needed forfur gene expression in megakaryoblastic cells. They also suggest that proper regulation of the fur gene in megakaryocytes has an impact on the activation of furin substrates involved in megakaryocyte maturation and platelet functions.

The convertase furin is involved in the maturation of key growth/aggregation mediators synthesized by the platelet producers, megakaryocytes, but the regulation of furin in these cells remains unknown. Computer-assisted search of the furin promoter sequence revealed multiple potential binding motifs for GATA-1, suggesting that furin is expressed and regulated in these cells. Using megakaryoblastic Dami cells, we observed that furmRNA expression increased gradually on phorbol 12-myristate 13-acetate–induced differentiation, reaching maximum levels (8.3-fold increase) at 10 days. Transient transfections with P1, P1A, or P1B fur-LUC–promoter constructs revealed that in Dami cells, the P1 promoter is the strongest and the most sensitive to forced expression of GATA-1. Coexpression of GATA-1 and its comodulator, Friend of GATA-1 (FOG-1), resulted in a cooperative increase in P1 activity. Deletion analysis indicated that important GATA-1–regulated sequences are located in the most proximal region of the P1 promoter. Further analysis revealed 2 potential GATA-binding motifs at positions −66 and +62. Point mutation of each of the 2 motifs indicated that the intactness of the first GATA site is required for full basal and GATA-1–stimulated promoter activity. Finally, the inhibition of furin activity through gene transfer of the inhibitor α1-AT-PDX led to a block in maturation of the furin substrates transforming growth factor-β1 and platelet-derived growth factor. Taken together, these results indicate that the most proximal GATA element in the P1 promoter is needed forfurgene expression in megakaryoblastic cells. They also suggest that proper regulation of the furgene in megakaryocytes has an impact on the activation of furin substrates involved in megakaryocyte maturation and platelet functions.

The temporal evolution of the ionizing UV background radiation field at high redshift provides a probe of the evolution of the early star formation rate. By comparing the observed levels of absorption in the highest redshift quasar spectra to the predictions of a hydrodynamic simulation, we determine the evolution of the photoionization rate (G) for neutral hydrogen in the intergalactic medium over the redshift range 4.9 [?] z [?] 6.1. After accounting for sampling variance, we infer a sharp increase in G from z [?] 6.1 to z [?] 5.8, probably implying reionization at this redshift. We find a decrease in G from z [?] 5.6 to 5.2 at 3 s significance. This feature is a generic signature in the aftermath of reionization, entirely consistent with the cosmological reionization process being completed at z ~ 6.1. This generic feature is a result of a significant change in the star formation rate subsequent to the cosmological reionization. There is an abrupt rise of the temperature of the intergalactic medium due to photoheating when it is reionized. This translates to a correspondingly sudden jump in the Jeans mass and a dramatic suppression of gas accretion onto the most abundant (subgalactic) halos at the epochs of interest. The star formation rate suffers a temporary setback in the aftermath of reionization, resulting in a temporary decrease in the amplitude of the ionizing radiation field.