Theoretical Threshold Research Articles

Maximum Doppler Frequency Detection Based on Likelihood Estimation With Theoretical Thresholds

Maximum Doppler Frequency Detection Based on Likelihood Estimation With Theoretical Thresholds

Strain distribution and electrical characteristics of flexible low-temperature polysilicon thin film transistors under biaxial bending

This paper investigates the strain distribution of flexible p-channel low temperature polycrystalline silicon thin film transistors under biaxial bending. The strain distribution of LTPS TFTs under different bending conditions is analysed by finite element analysis. \U0001d6c6r and \U0001d6c6θ are essentially equal and constant within the load ring. The finite element analysis shows that when the biaxial bending strain condition is 2.5%, the strain distribution is mainly concentrated at the contact angle between the electrode and the oxide layer. This strain is significantly greater than the overall strain of the device, which is the main reason for the bending performance of the device. We found that under biaxial bending, the threshold voltage shifts towards the negative axis as the biaxial strain increases. Within this strain range, these electrical properties are evident under biaxial strain conditions. Comparing theoretical threshold voltage shifts based on energy band changes with experimental results under biaxial strain, it was found that changes in trap density should also contribute to the threshold voltage shift.

Nonlinear decay of high-power microwaves into trapped modes in inhomogeneous plasma

We present novel experimental evidence of parametric decay instability of microwave beams in the plasma edge of the Wendelstein 7-X stellarator. We propose that the instability is sustained by trapping of only one daughter wave in the non-monotonic density profile measured with high spatial resolution within a stationary magnetic island. The power levels and spectral shapes of the detected microwave signal are reproduced by numerical modelling and a theoretical power threshold is predicted around 300 kW, comparable with observations. We predict a fraction of power drained by daughter waves around 4% in the experiments, potentially increasing above 50% for more hollow edge density profiles. Such absorption levels could significantly reduce the efficiency of the microwave heating and current-drive system in tokamaks and stellarators.

Misclassification of nodal stage in gastric cancer: 16 lymph nodes is not enough

BackgroundIn gastric cancer, nodal stage plays an important role. Insufficient lymph node harvesting or incomplete examination may lead to misclassification and affect postoperative strategy and group survival. This study’s objective was to determine the minimum number of examined lymph nodes needed in gastric cancer and compare this to the minimum lymph node count according to the current Union for International Cancer Control (UICC) classification using real world data.MethodsBased on anatomical data, expected mean lymph node counts and their 95% confidence intervals for complete D2 lymphadenectomy were calculated. Using stochastic analysis, a threshold for correct classification in 95% of cases was determined. Survival data of nodal negative gastric cancer patients was extracted from the Surveillance, Epidemiology, and End Results (SEER)-Database for 2010–2017. Patients reaching at least the calculated theoretical threshold were compared to the minimum threshold according to the current UICC classification.ResultsThe expected lymph node count was 30 (95% CI: 28–32; range 17–52), corresponding to a 27 lymph nodes. In nodal negative patients with exactly 16 and at least 27 examined lymph nodes, relative 5 year survival was 79 and 89% in T1/T2 and 39 and 64% T3/T4 gastric cancer, respectively. Theoretically, when only 16 lymph nodes are analyzed, nodal negative staging may be incorrect in up to 47% of cases.ConclusionsA minimum threshold of 16 examined lymph nodes cannot be justified. Retrospective analysis confirmed systematic misclassification of patients with insufficient lymphadenectomy in nodal negative gastric cancer patients. Correct lymphadenectomy and thorough examination of the surgical specimen is mandatory.

Humoral immune response after COVID-19 infection or BNT162b2 vaccine among older adults: evolution over time and protective thresholds

The objectives of this study were to assess the dynamics of the SARS-CoV-2 anti-RBD-IgG response over time among older people after COVID-19 infection or vaccination and its comparison with indicative levels of protection. Geriatric patients with SARS-CoV-2 serological test results were included and divided into three groups. A vaccine group (n = 34), a group of natural COVID-19 infection (n = 32), and a group who contracted COVID-19 less than 15 days after the first injection (n = 17). Eighty-three patients were included; the median age with IQR was 87 (81–91) years. In the vaccine group at 1 month since the first vaccination, the median titer of anti-RBD-IgG was 620 (217–1874) BAU/ml with 87% of patients above the theoretical protective threshold of 141 BAU/ml according to Dimeglio et al. (J Infec. 84(2):248–88, [7]). Seven months after the first vaccination, this titer decreased to 30 (19–58) BAU/ml with 9.5% of patients > 141 BAU/ml. In the natural COVID-19 infection group, at 1 month since the date of first symptom onset, the median titer was 798 (325–1320) BAU/ml with 86.7% of patients > 141 BAU/ml and fell to 88 (37–385) with 42.9% of patients > 141 BAU/ml at 2 months. The natural infection group was vaccinated 3 months after the infection. Five months after the vaccination cycle, the median titer was 2048 (471–4386) BAU/ml with 83.3% of patients > 141 BAU/ml. This supports the clinical results describing the decrease in vaccine protection over time and suggests that vaccination after infection can maintain significantly higher antibody titer levels for a prolonged period of time.

Definition, Operationalisation, and Measurement of Leadership Strategy: Application in the Banking Sector in Kenya

This paper aimed to define, operationalise, and generate measures of leadership strategy that can inform future empirical enquiry and analysis. In addition, the paper aimed to provide a conceptualisation of the notion of leadership strategy, situating the concept within the broader leadership strategy literature from which a working definition of leadership strategy is coined. From the definition, leadership strategy was then operationalised by developing a set of items that can be used to measure it. The items were subsequently subjected to empirical evaluation and testing within the context of the banking sector in Kenya. Using SmartPLS software, Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were performed on questionnaire data collected online from 184 senior managers of 12 banks listed in the Nairobi Securities Exchange. The factors or indicators were validated with high scores of exploratory factor analysis and confirmatory factor analysis. All factors/indicators were validated and found to be consistently above theoretical thresholds. The study proposed an inventory for measuring leadership strategy using 24 Likert-scale items based on the empirical results. It is worth mentioning that while the items were validated in the banking sector context, each item is a generic measure of the corresponding factors and can be adapted for use in other research contexts. The paper established an empirical lead towards the proposition of an inventory for the construct of leadership strategy.

Crack front instability in mixed-mode I+III: The influence of non-singular stresses

In a previous paper (Leblond et al., 2011), a theoretical instability threshold was derived for the currently observed phenomenon of crack front fragmentation under mixed-mode I+III loading conditions. Instability modes were shown to emerge when the mode mixity ratio KIII0/KI0 exceeds some critical value [KIII0/KI0] that only depends on Poisson’s ratio. Unfortunately, the predicted threshold was found to be much larger than that observed in general. Numerical simulations of crack front fragmentation (Chen et al., 2015), based on a phase-field model, subsequently evidenced an important role of the specimen size on the non-coplanar instability. Here, we explore theoretically the influence of existence of some finite characteristic length(s), arising from the loading, by accounting for the presence of non-singular stresses Tij0 in the unperturbed configuration of the crack. By re-examining the linear stability analysis of Leblond et al. (2011) with these more general assumptions, we show that a negative non-singular stress Txx0 in the direction of propagation does not affect crack front fragmentation, while a negative non-singular Tzz0 in the direction of the crack front strongly hampers it. On the contrary, positive non-singular stresses Txx0 and Tzz0, or non-zero non-singular (antiplane shear) stresses Txz0, promote the fragmentation process, sometimes through the formation of facets that drift along the front as propagation proceeds. Large values of all three of these non-singular stresses may result in a significant lowering of the threshold value [KIII0/KI0] of the mode mixity ratio for instability, even possibly down to zero; which stresses out the potential existence of the fragmentation instability even in pure mode I. Yet, our results cannot explain the often observed formation of non-coplanar facets at extremely low mode mixity ratios; indeed the wavelength of the instability modes predicted are comparable to the finite characteristic length(s) introduced, of at least centimetric order of magnitude, while the formation of facets has been observed experimentally at scales as low as some tens of microns.

Nanofibers Comprising Interconnected Chain‐Like Hollow N‐Doped C Nanocages as 3D Free‐Standing Cathodes for Li–S Batteries with Super‐High Sulfur Content and Lean Electrolyte/Sulfur Ratio

The development of a suitable cathode host that withstands high sulfur content/loading and low electrolyte/sulfur (E/S) ratio is particularly important for practically sustainable Li-S batteries. Herein, a facile approach is utilized to prepare free-standing 3D cathode substrates comprising nitrogen-doped carbon (N-C) scaffold and metal-organic framework derived interconnected chain-like hollow N-C nanocages, forming a highly porous N-C nanofiber (HP-N-CNF) framework. The N-C skeleton provides highly conductive pathways for fast lithium ion/electron diffusion. The hollow interconnected N-C nanocages not only offer enough space to absorb a high volume of active material but also effectively channelize severe volume stress during the electrochemical performance. The Li-S cell utilizing HP-N-CNF as cathode host displays exceptional battery parameters with high effective sulfur content (83.2 wt%), ultrahigh sulfur loading (14.3 mg cm-2 ), and low E/S ratio (6.8 μL mg-1 ). The Li-S cell exhibits a maximum areal capacity of 12.2 mAh cm-2 which stabilizes at ≈5.5 mAh cm-2 after the 130th cycle at 0.05 C-rate and is well above the theoretical threshold. Therefore, the proposed unique nanostructure synthesis approach would open new frontiers for developing more realistic and sustainable host materials with feasible battery parameters for various energy storage applications.

A temperature‐dependent phenology model for Apanteles subandinus Blanchard, parasitoid of Phthorimaea operculella Zeller and Symmetrischema tangolias (Gyen)

AbstractThe potato tuber moth (Phthorimaea operculella Zeller) is a major invasive pest of potato (Solanum tuberosum L.) worldwide. Classical biological control using parasitoids had been of primary interest during the last decades to control this pest. More than twenty parasitoid species have been reported parasitizing P. operculella. Apanteles subandinus Blanchard had been successfully used in different countries. Determination of the parasitoid's temperature‐dependent development is crucial for better predicting the potential of the parasitoid to establish in a new region and to control the target pest. Therefore, the effect of temperature on the development and reproduction of A. subandinus was studied at five constant temperatures ranging from 11–30°C in its main host P. operculella. The Insect Life Cycle Modeling (ILCYM) software was used to fit nonlinear equations to collected life table data and to establish an overall phenology model to simulate life table parameters based on temperature. The parasitoid completed its life cycle at constant temperatures from 15 to 30°C. Temperature of 11°C was lethal to pupae, and at 35°C no larvae development was possible. The theoretical lower threshold temperatures for the development of egg‐larvae and pupae were 10.3°C and 11.8°C respectively. The model predicted limits for survival at around 12°C and 33°C. The lowest senescence rate was observed within the temperature range of 15–25°C. Oviposition time decreased significantly with increasing temperature from 12.2 days (15°C) to 1.8 days (30°C). The highest fertility was predicted at 27°C. Maximum population growth is expected around 26.78°C with a finite rate of increase, λ of 1.0445, which corresponds to a population doubling time of 15.9 days. The highest values for gross reproduction rate (GRR) and net reproduction rate (R0) were found between 24 and 25°C, and the shortest mean generation time (T) was observed at 30°C (23.48 d). The use of the phenology model in the context of classical biological control of P. operculella is discussed.

Optimal Power Allocation for Channel-Based Physical Layer Authentication in Dual-Hop Wireless Networks.

Channel-based physical-layer authentication, which is capable of detecting spoofing attacks in dual-hop wireless networks with low cost and low complexity, attracted a great deal of attention from researchers. In this paper, we explore the likelihood ratio test (LRT) with cascade channel frequency response, which is optimal according to the Neyman–Pearson theorem. Since it is difficult to derive the theoretical threshold and the probability of detection for LRT, majority voting (MV) algorithm is employed as a trade-off between performance and practicality. We make decisions according to the temporal variations of channel frequency response in independent subcarriers separately, the results of which are used to achieve a hypothesis testing. Then, we analyze the theoretical false alarm rate (FAR) and miss detection rate (MDR) by quantifying the upper bound of their sum. Moreover, we develop the optimal power allocation strategy between the transmitter and the relay by minimizing the derived upper bound with the optimal decision threshold according to the relay-to-receiver channel gain. The proposed power allocation strategy takes advantage of the difference of noise power between the relay and the receiver to jointly adjust the transmit power, so as to improve the authentication performance on condition of fixed total power. Simulation results demonstrate that the proposed power allocation strategy outperforms the equal power allocation in terms of FAR and MDR.

A COVID-19 vaccination model for Aotearoa New Zealand

We develop a mathematical model to estimate the effect of New Zealand’s vaccine rollout on the potential spread and health impacts of COVID-19. The main purpose of this study is to provide a basis for policy advice on border restrictions and control measures in response to outbreaks that may occur during the vaccination roll-out. The model can be used to estimate the theoretical population immunity threshold, which represents a point in the vaccine rollout at which border restrictions and other controls could be removed and only small, occasional outbreaks would take place. We find that, with a basic reproduction number of 6, approximately representing the Delta variant of SARS-CoV-2, and under baseline vaccine effectiveness assumptions, reaching the population immunity threshold would require close to 100% of the total population to be vaccinated. Since this coverage is not likely to be achievable in practice, relaxing controls completely would risk serious health impacts. However, the higher vaccine coverage is, the more collective protection the population has against adverse health outcomes from COVID-19, and the easier it will become to control outbreaks. There remains considerable uncertainty in model outputs, in part because of the potential for the evolution of new variants. If new variants arise that are more transmissible or vaccine resistant, an increase in vaccine coverage will be needed to provide the same level of protection.

A numerical and theoretical study of the multipactor appearance in the presence of a DC parallel electric field

In this paper, we study the appearance of the multipactor in a simple system with a bottom plate holding a static potential Vd. We developed a numerical model to compute the evolution of the multipactor threshold as a function of the potential. We identify the nature of the resonant modes that appear at different Vd using resonance theory. Then, we use it to compute the theoretical threshold of the structure. As we use a very simplistic electron emission model to identify the multipactor modes, we compute the threshold in a more realistic configuration in a second step.

Rumor Dynamic Model considering Intentional Spreaders in Social Network

The development of network technology has created various platforms and methods for information dissemination. When rumors spread in social networks, they will rapidly spread and may cause social harm. Also, there are groups in social networks that create and spread rumors for the purpose of profit, thus expanding the scope of rumors. Therefore, based on the theory of complex network propagation dynamics, the study of the propagation law of rumors and the design of effective prevention and control strategies is of practical importance and theoretical significance for understanding the propagation laws of rumors and controlling the outbreak of rumors. The spreading process of rumors on social network platforms is focused here. The intentional spreader based on the classic rumor‐spreading model is introduced. First, 2SIR rumor‐spreading models on homogeneous and heterogeneous networks are established, respectively. Second, the steady‐state analysis was separately carried out, and the corresponding propagation critical value was obtained: in the homogeneous network, the condition for the large‐scale spread of rumors is ; in the heterogeneous network, the condition for the large‐scale spread of rumors is . Finally, the simulation calculation and model feasibility verification were carried out on the model. The results show that the theoretical propagation threshold corresponds with the simulation results. According to the simulation results, the final influence of rumors has significantly decreased with decreasing values of β (intentional spreading rate) instead of α (unintentional spreading rate). It can be concluded that in the real‐life rumor control process, more resources need to be invested in reducing the rate of intentional transmission instead of being indiscriminately put on controlling all spreaders of rumors.

Absolute stimulated Brillouin side scattering in an inhomogeneous flowing plasma.

Theory of absolute stimulated Brillouin side scattering in an inhomogeneous flowing plasma is presented and verified numerically. The linearized coupling equations are transformed into a Schrödinger equation in k space and solved as an eigenvalue problem. Analytic threshold, growth rate, and scattering geometry are obtained for the pump laser with arbitrary incidence angle. Numerical solutions of the coupling equations show good agreements between the theoretical and numerical absolute thresholds when ion-acoustic wave damping is not too large, and thus an old but famous threshold in [Phys. Fluids 17, 1211 (1974)PFLDAS0031-917110.1063/1.1694867] is corrected. It also indicates that the theoretical analysis is not accurate for strong dampings, since it will overestimate the absolute threshold. Possibility of finding such instability in the current experiments is also discussed.

Inducing thermionic emission from lanthanum hexaboride probes in Magnum-PSI

For thermionic emission rates exceeding the incident plasma electron flux, recent theory proposes an inverse sheath regime, with promising properties for future application in fusion edge plasmas. With the aim of inducing thermionic emission in fusion-relevant plasma conditions, several lanthanum hexaboride probes were heated in the linear plasma generator Magnum-PSI. During exposures at low plasma power and additional pulsed laser heating, the probe’s floating potential was reduced by up to 12%, providing a possible indication of thermionic emission. However, these observations coincided with rapid erosion of probe material, attributed to enhanced lanthanum self-sputtering. During follow-up experiments with helium plasmas at electron temperatures around 1 eV, the lanthanum ion impact energy and sputtering yield were reduced, and rapid erosion was avoided, thus confirming the thesis of self-sputtering. A parameter scan of plasma power resulted in LaB 6 surface temperatures up to 2450 °C, exceeding the theoretical inverse sheath threshold temperature by over 300 °C. However, the probe’s floating potential did not deviate from reference measurements using a probe with high electronic work function, indicating absence of strong thermionic emission. This apparent discrepancy is attributed to the effects of probe surface modifications as observed during these experiments: impurity deposition, erosion and cavity formation. These modifications possibly affected the LaB 6 electronic work function, thereby keeping the inverse sheath threshold out of reach. In conclusion, although LaB 6 has one of the lowest work functions available, the inverse sheath threshold conditions could not be reached with the present setup in Magnum-PSI. Surface modifications thus do form a limiting factor for the application of LaB 6 in fusion-relevant plasma conditions. Moreover, the window of stable operation for LaB 6 in dense hydrogen plasmas is limited below ∼ 1.5 eV, and does not overlap with the conditions expected in the edge region of future fusion devices like ITER. • LaB 6 probes were heated up to 2450 °C under fusion-relevant plasma conditions. • Surface modifications limit the effective operation of powder-pressed LaB 6 . • Lanthanum self-sputtering in dense plasma conditions leads to rapid erosion. • The LaB 6 operation window does not overlap with ITER divertor conditions.

Cumulative downstream turbine‐induced mortality and thresholds for facilitating upstream passage of American eel

AbstractAmerican eels (Anguilla rostrata) are vulnerable to turbine‐induced mortality during outmigration along regulated rivers. Turbine‐induced mortality is cumulative when multiple facilities are encountered along the route. This level of mortality may be unsustainable such that facilitating upstream movement ostensibly for recovery purposes, may in fact be detrimental to the population or an ecological trap. The objectives of this study were to estimate a theoretical threshold for facilitating upstream movement passed hydroelectric facilities and estimating cumulative turbine mortality within waterbodies across American eel's historical range within Ontario, Canada. A stage‐structured model was used to estimate mortality thresholds parameterized by published life stage survival probabilities using a maternal effect and altering silver eel survival to mimic turbine mortality. The threshold was exceeded when population growth (λ) declined below 1.0. Site mortality was estimated based on the generating station characteristics including turbine type, size, proportion of flow through turbines, and sluice gate height. Cumulative mortality within a waterbody was projected using a Bayesian network (i.e., conditional probability) and the calculated site‐specific mortality. The survival required for a stable population using the stage‐structured model was 0.75; (0.65–0.85) therefore, annual mortality greater than 0.25 (0.15–0.35) would result in population decline (λ < 1). The effects of turbine mortality increased with additional hydroelectric facilities encountered along the route. Across Ontario, there was no eel habitat deemed to be safe in terms of levels of cumulative turbine mortality during outmigration. Moreover, 89.1% of eel habitat was considered to be within the cautionary range of turbine mortality, whereas 10.9% of eel habitat was considered to be above the threshold for sustainable passage during outmigration. Lake Ontario accounted for 98.2% of the area within the cautionary range, whereas most of the tributaries and watersheds associated with the Ottawa River and Lake Ontario were above the threshold.

How Much Information Is Required to Time the Market?

In this article, the authors present an analytical explanation for why it can be difficult to devise a successful market timing strategy. The authors derive formulas to estimate the minimum required information coefficient for a timing strategy to outperform a buy-and-hold market benchmark, both with and without an alpha target. They show that markets with high Sharpe ratios and those that have low volatility are by nature hard to time. They also show that having high market exposure in a market timing strategy is generally beneficial; however, there can be a critical point beyond which additional market exposure makes timing more difficult. The authors extend the model to cover practical considerations such as transaction costs, skewness and fat tails, and market timing with two correlated assets. Finally, they present a case study to illustrate how investors could apply their framework to choose the optimal market exposure in a market timing strategy using the S&amp;P 500. <b>Key Findings</b> ▪ Under a bivariate normal framework, the authors show that the expected return of a timing strategy comes in two additive parts: one part driven by timing information and the other driven by average market exposure. ▪ There is generally a theoretical nonzero information threshold for a timing strategy to beat a buy-and-hold benchmark. This threshold can serve as a useful guide to determine whether a timing strategy is likely to succeed, complementing historical backtests. ▪ Although an investor can increase timing strategy return by increasing average market exposure without having more timing information, the difficulty of beating a buy-and-hold benchmark with an alpha target increases dramatically as average market exposure becomes very high.

Cardiovascular disease in an intensive care unit: patterns of an often fatal omen

Abstract Background Care for the critically ill patient with Cardiovascular Disease (CVD) requires a unique management approach, as the theoretical critical threshold for decompensation is lower and inherent adaptive mechanisms may be compromised. We aimed to characterize the prognostic impact of CVD in patients admitted to an Intensive Care Unit (ICU). Methods We performed a cohort study of consecutive patients admitted to an ICU from January to December 2019. Patients were stratified as follows: (1) established CVD – presence of either atrial fibrillation, heart failure, coronary artery disease and/or peripheral artery disease; (2) at higher risk of CVD – known arterial hypertension, dyslipidemia, diabetes mellitus and/or current smoking, in the absence of established CVD; and (3) at lower risk of CVD – i.e. none of the above. The co-primary endpoints were all-cause death in ICU and death during index hospitalization. Results During 2019, there were 334 admissions in ICU, comprising a total of 296 patients (mean age 67±15 years, 58.1% male). Overall, 69 (23.3%) and 108 (36.5%) died in ICU and during index hospitalization, respectively. Compared to patients at lower risk of CVD, those at higher CVD risk or with established CVD had markers of more severe disease, as noted by higher risk scores (e.g., SAPS-II 35.0±20.0 vs. 43.5±22.3 vs. 52.6±20.0; p&amp;lt;0.001), higher rates of mechanical ventilation (41.5 vs. 57.3 vs. 63.9%; p=0.020), shock during ICU stay (34.0 vs. 52.7 vs. 66.9%; p&amp;lt;0.001) and acute kidney injury (26.4 vs. 35.5 vs. 57.9%; p&amp;lt;0.001), respectively, as well as higher death rates in ICU (5.7 vs. 21.8 vs. 31.6%; p=0.001) and index hospitalization (9.4 vs. 37.3 vs. 46.6%; p&amp;lt;0.001). In multivariate analysis, adjusted for age and cause of admission, established CVD independently predicted the risk of all-cause death in ICU (HR: 2.084; 95% CI: 1.136–3.823; p=0.018) and during index hospitalization (HR 1.712; CI: 1.009–2.889; p=0.046). The analysis for the group of patients at higher risk of CVD yielded similar results to the abovementioned. Conclusion Roughly 4 in every 5 patients admitted in ICU were at risk of or had established CVD. The presence of either of the above independently predicted a two- to three-fold higher risk of death during hospitalization. Our findings emphasize the considerable burden of CVD in ICU and underscore the importance of comprehensive management of the complex critically ill patient. Funding Acknowledgement Type of funding sources: None.

Pharmacokinetics of Single-Dose Intramuscular and Subcutaneous Injections of Buprenorphine in Common Marmosets (Callithrix jacchus).

Although buprenorphine is the most frequently used opioid analgesic in common marmosets (Callithrix jacchus), there is limited information in the literature supporting current dosing regimens used for this species. The purpose of this study was to determine the pharmacokinetic profiles of single-dose buprenorphine HCl administered intramuscularly (IM) at 0.01 mg/kg in 6 adult marmosets (1.8 to 12.8 y old; 2 males, 4 females) and subcutaneously (SQ) at 0.01 mg/kg in 6 adult marmo- sets (2.3-4.4 y old; 3 males, 3 females) by mass spectrometry. Blood was collected at multiple time points from 0.25 to 24 h from unsedated animals following a hybrid sparse-serial sampling design. The maximal observed plasma concentration of buprenorphine (Cmax ) administered IM (2.57 ± 0.95 ng/mL) was significantly higher than administered SQ (1.47 ± 0.61 ng/mL). However, the time to Cmax (Tmax) was not statistically different between routes (17.4 ± 6 min for IM and 19.8 ± 7.8 min for SQ). The time of the last quantifiable concentration of buprenorphine was 5 ± 1.67 h for IM compared with 6.33 ± 1.51 h for SQ, which was not statistically different. The mean buprenorphine plasma concentration-time curves were used to propose a dosing frequency of 4 to 6 h for buprenorphine at 0.01 mg/kg IM or SQ based on a theoretical therapeutic plasma concentration threshold of 0.1 ng/mL. Based on the mean pharmacokinetic parameters and plasma-concentration time curves, both IM and SQ routes of buprenorphine at this dose provide a rapid increase in the plasma concentration of buprenorphine above the therapeutic threshold, and may be more effective for acute rather than long-lasting analgesia. Further studies are needed to examine repeated dosing regimens and the efficacy of buprenorphine in common marmosets.

A generic crystallopathic model for chronic kidney disease progression.

Chronic kidney disease (CKD) has reached epidemic proportions globally. The natural course of chronic kidney disease is almost uniformly progressive, albeit at different rates in different individuals. The downhill course appears to pervade kidney diseases of all etiologies and seems to spiral down a self-perpetuating vortex, even if the original insult is ameliorated or controlled. In this issue of the JCI, Shiizaki, Tsubouchi, and colleagues proposed a model of renal tubule luminal calcium phosphate crystallopathy that accounts for renal function demise. Calcium phosphate crystals attached to TLR4 and underwent endocytosis at the brush border, triggering inflammation and fibrosis. This mechanism might operate in different kinds of kidney disease, with a theoretical phosphate concentration threshold in the proximal tubular lumen, beyond which is triggered undesirable downstream effects that eventuate in loss of renal function. If this model parallels human CKD, clinicians may focus efforts on determining phosphate exposure in the proximal tubular lumen.