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Spontaneous adrenal haemorrhage (SAH) is a rare condition. The incidence of adrenal haemorrhage in pregnancy is currently not known; however, an association with pregnancy has been reported.An acute presentation with severe back or flank pain should raise suspicion of this condition. Diagnosis is based on imaging. An ultrasound scan is a basic and readily available investigation in pregnancy to rule out renal and suprarenal pathology while CT or MRI scan can help to confirm the diagnosis. A multidisciplinary team (MDT) approach, involving the obstetric, anaesthetic, medical and endocrine team, is essential in management of this condition.We present a case of an SAH; managed conservatively, in an otherwise healthy and low-risk pregnant woman and describe the literature review on this rare condition, including pathophysiology and management.

Background: Anaemia is most common hematological issue encountered during pregnancy and one of the major cause for maternal and perinatal morbidity due to disturbed physiological milieu. Our objective was to study the pregnancy outcome in women with severe anaemia in labour. Method: A Prospective observational study was conducted by collecting data from medical records of around 100 consecutive consenting women with severe anaemia in labour with >28weeks of pregnancy which admitted in a labour room of a tertiary health care center of south Gujarat over a period of one year after HREC approval. Results: In our study Majority of the subjects (73 %) were in the age group of 19 – 29 years, Majority (70%) subjects were unbooked. 75% subjects were with severe anaemia (Hb = 4 – 7 gm/dl) and 25% subjects were of very severe anaemia (Hb < 4 gm/dl). Majority of the (69 %) subjects were multipara and (31%) subjects were primipara. In multipara, majority (73.91%) subjects were having < 2 years of birth spacing interval. 84% subjects had microcytic hypochromic anaemia. 62% subjects had vaginal delivery and 36% subjects were undergone for Emergency LSCS. Conclusion: Increasing utilization of healthcare facility at every step(rural/urban) by needy women can improve obstetric & perinatal outcome associated with maternal anaemia. To overcome complications of anemia during pregnancy & in labour early detection of cases & early catching of mild to moderate cases of anaemia & their timely management required. All these can improve our clinical & Reproductive outcome

Aims: This article analyzes an inventory system for deteriorating items. The demand is quadratic function of time and is dependent on time, price and advertisement. Shortages are allowed and partially backlogged. Background: Demand and pricing are the two most crucial factors in inventory policy for any business to be successful. In today’s era of competitive circumstances, any product is promoted through advertisement, which plays a vital role in changing the demand pattern among the community. The marketing and demonstration of an item by time-to-time with fashionable advertisements through well-known media such as TV, radio, newspaper, magazine, etc. However, this idea is not always true for some goods like wheat, vegetables, fruits, food grains, medicines and other perishable goods due to their deteriorating nature and this in turn decreases demand for such goods. Deterioration may define as decay, damage, spoilage, evaporation, obsolescence, pilferage. Hence, deterioration effect is a major part in inventory control theory. So in this article demand rate is considered to be a function of selling price, time and occurrence of advertisement instantaneously. Objective: A solution procedure is obtained to find optimal number of price changes and optimal selling price to maximize the total profit. Method: Classical Optimization. Result: From the sensitivity analysis table, it can be seen that the optimal profit is highly sensible to advertisement coefficient and purchase cost. With an increment in rate of deterioration, selling price decreases. Scale demand has reasonable effect on cycle time and selling price. When the value of increase, the cycle length and profit goes on decreasing. Growth in profit is observed if we increase parameter b, higher will be the profit. Price elasticity is sensible parameter with respect to selling price. If backlogging rate increases, the profit will decreases. The inventory parameters holding cost, back order cost and lost sale cost have marginal effect on total profit. Conclusion: In this article, an inventory model is proposed for deteriorating items with variable demand depends upon the advertisement, selling price of the item and time. Shortages are allowed and partially backlogged and backlogging rate depends on the waiting time for the next replenishment. From this article, we can conclude that the parameters are insensible with respect to optimal profit, cycle time and selling price and rest of the parameters have practical output on total profit.

Hexokinase is an enzyme involved in the glucose metabolism pathway. Magnesium is an inherent cofactor of the Hexokinase enzyme. The plethora of literature suggested that hexokinase level was decreased in diabetic rats. Sodium metavanadate shows insulin-mimetic action. We designed this work to determine the effect of magnesium on diabetes and associated vascular complications in rats. Type-2 diabetes was induced by a high-fat diet and a low dose of streptozotocin.. Diabetic rats were divided into groups, i.e. normal, diabetic, magnesium sulfate, sodium metavanadate, a combination of glibenclamide and metformin, a variety of sodium metavanadate with glibenclamide and metformin, and a combination of magnesium sulfate with glibenclamide and metformin. Magnesium sulfate was used as a hexokinase activator. Blood glucose levels were measured before initiation, between, and after 4 weeks of treatment. Biochemical and tissue parameters were estimated for additional confirmation. A vascular study took the contractile response of hydrogen peroxide in rat thoracic aortas of different groups. Statistical comparisons between groups were performed by two-tailed one-way ANOVA followed by the Dunnett test. P-values

Inventory model for vaccine of COVID-19 pandemic is the subject of analysis in the proposed article. The initial registration for vaccination and vaccination of registered individuals is taken during the period under consideration. The paper considers the utility of vaccine during storage, holding cost, purchase cost, manufacturing cost and inspection cost. A fraction of registered individuals who do not turn up for a vaccination is taken into account. All the actions by the player incur carbon emissions. During the whole procedure of vaccination starting from raw material to end user carbon emissions are observed. Carbon emissions in stocking raw material, during inspection, during purchase activity, during set-up and transportation phase and holding it at point of delivery. Maximum carbon emission of 28% occur during purchase activity followed by 21% during transportation at the point of delivery and stocking it at respective places. To follow green policy, carbon tax is levied. A non-linear formulation of the proposed problem is modelled to compute optimum cycle time without allowing shortages. The convexity of the objective function is established through the numerical data. Analysis of carbon emissions and carbon tax levied is carried out through the data. Research Objective: Carbon Emission is one of a cause for ozone layer depletion. Moreover, it causes many ecological disturbances resulting into several environmental temperature variations. These all problem affect an individual’s health. So, there arise a need to frame a mathematical model to decipher relationship between COVID-19 vaccine inventory and effect of carbon emissions.

Interleukin-12 (IL-12) is a proinflammatory cytokine, which bridges innate and adaptive immunity via induction of T helper 1 differentiation and promotes cytolytic activity of natural killer and T cells. IL-12 has demonstrated potent antitumor activity in syngeneic mouse models and promising anti-tumor efficacy in humans. However, development of IL-12-based treatments has been limited by severe systemic toxicities in the clinical setting. To overcome toxicity and potentially improve the therapeutic index of IL-12 in a clinical setting, XTX301 was engineered as a half-life extended and masked IL-12. The masking domain of XTX301 is designed to pharmacologically inactivate IL-12 in circulation and non-tumor tissue, while enabling generation of an active IL-12 moiety upon cleavage of a linker sequence by matrix metalloproteinases that are enriched in the tumor microenvironment. To confirm the ability of human tumor associated proteases to activate XTX301, cleavage was assessed in primary human tumor samples and in plasma from cancer patients. We observed cleavage of XTX301 in the majority of human tumors samples tested, but no activation was observed in plasma from cancer patients. Human IL-12 does not bind and signal through the mouse IL-12 receptors, hence three murine surrogates were created for in vivo studies: mXTX301, a non-cleavable control, and an unmasked control molecule. Tumor growth inhibition was observed after a single dose of mXTX301 as low as 0.039 mg/kg. The non-cleavable form of mXTX301 was less potent than mXTX301, demonstrating that the anti-tumor activity of mXTX301 is dependent on protease activation. The unmasked control was not well tolerated, with a > 20% body weight loss observed by Day 6, resulting in 75% of animals being euthanized by Day 11. Unlike the unmasked control, mXTX301 was well-tolerated at all tested doses, as evidenced by no loss in animals’ body weights, and demonstrated minimal pharmacodynamic activity in non-tumor tissues. In tumors, mXTX301 stimulated the infiltration of cytotoxic CD8+ T cells and induced the expression of several immune-related genes including those associated with IFN-γ cell signaling, antigen processing and presentation, and defense response as well as enrichment of gene signatures for T cells, natural killer (NK) cells, macrophages and dendritic cells as determined by RNA sequencing. In non-human primates, the highest non-severely toxic dose of XTX301 was 2mg/kg dosed weekly for a total of 4 doses. In summary, a half-life extended tumor-activated IL-12 molecule, mXTX301, demonstrated anti-tumor activity in preclinical mouse models with improved tolerability compared to a systemically active IL-12 molecule suggesting that XTX301 has potential for exerting potent anti-tumor activity while widening the therapeutic index of IL-12 treatment. Citation Format: Natalia Malkova, Ekta Patel, Sallyann Vu, Damiano Fantini, Rebekah O'Donnell, Manoussa Fanny, Justin Greene, Wilson Guzman, David Crowe, Stephanie Hsiao, Parker Johnson, Megan McLaughlin, Oleg Yerov, Kurt Jenkins, Katarina Halpin-Veszeleiova, Hanumantha Rao Madala, Caitlin O'Toole, Jake Taylor, Magali Pederzoli-Ribeil, Benjamin Nicholson, Carl Uli Bialucha, Jennifer E. O'Neil. A half-life extended, tumor-activated IL-12 increased the infiltration of effector immune cells into the tumor microenvironment and demonstrated anti-tumor activity in syngeneic mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 587.

The model deals with the stock-dependent demand as exhibiting a huge volume of commodities leads to draw more costumers and augment the trading of the goods. Objects like vegetables, fruits, medicines start getting deteriorate after some period of time that results in economical and financial loss. By taking care of this factor a constant deterioration rate is considered as controllable by the use of suitable preservation technologies. Preservation technology investments are made for a valuable business as it helps to decrease the rate of deterioration. This model allows shortages, and back-ordering is permissible to manage the loss that occurs due to perishable objects and shortages. The objective is to find the optimal cycle time, preservation technology cost, and positive inventory time. The paper also proves the convexity of the total cost through graphs with respect to decision variables. A sensitivity analysis of decision variables, with respect to different inventory parameters, is carried out to modify the model.

Examine social media experiences of the suicidal adolescent presenting to the Emergency Department with an acute mental health crisis.We used qualitative interviews to obtain in-depth understanding of both negative and positive impacts of social media use on acute adolescent suicidal behavior. A bilingual transcriptionist transcribed audio recordings. Three investigators independently reviewed transcripts to identify themes and develop initial coding scheme through "open coding." Using grounded theory, data collection proceeded along with cultivation of themes until thematic saturation was achieved. Thematic saturation was determined when no new themes were generated from the data. Data were coded in Dedoose software to facilitate reporting of themes and quotes. Techniques to ensure trustworthiness included iterative data collection, use of a coding framework, and multiple coders.Seventeen interviews were conducted from May to October 2020. Median participant age was 15 years. Twenty-four percent were of Hispanic ethnicity and 82% identified as cisgender. Major themes include distraction from negative emotions; facilitated communication resulting in improved social connectedness; metric of connectedness; comparison of self to others; and desensitization and normalization to suicidal acts. Minor theme of increased time on social media is also discussed. These themes echoed components of current suicide theory.Acutely suicidal adolescents report social media experiences that reflect themes of social alienation and learned capacity for suicidal acts. Themes echo components of current suicide theory. Our participants also reported positive uses of social media. These protective experiences should be leveraged to inform strategies to interrupt behaviors leading to acute suicidality.This study brings to the literature direct accounts of suicidal adolescents and their lived experiences with social media at the point of a mental health emergency. These experiences can inform strategies to interrupt behaviors leading to suicidality.

This chapter examines the illegal wildlife trade (IWT) in the Mekong, with particular attention to how political economic factors and legal structures shape actors’ interests and incentives. The current literature on wildlife trafficking mainly attributes wildlife protection failures to weak enforcement. However, this literature has paid little attention to the underlying factors that contribute to the weak enforcement of wildlife laws. This chapter applies a political economy analysis to better understand the role of each actor from the point of wildlife sourcing to end consumption. It also explains why effectively enforcing wildlife laws is difficult and is often not in the interest of wildlife officials. This chapter thus examines why actors along IWT supply chains engage in illegal activities and do not abide by conservation laws. With rising demand for wildlife products, particularly because of increasing economic prosperity, the survival of many endangered species is under threat. Despite growing calls for total bans of wildlife trade or trade regulations to prevent overharvesting, these frequently fail to achieve conservation goals if they do not consider the local political economy context. This chapter focuses on the global IWT hotspots of Vietnam, Laos, and Cambodia, analyzing how legal frameworks shape local political economies and showing why IWT is a pervasive problem in the region.

Triangulum, M33, is a low mass, relatively undisturbed spiral galaxy that offers a new regime in which to test models of dynamical heating. In spite of its proximity, the dynamical heating history of M33 has not yet been well constrained. In this work, we present the TREX Survey, the largest stellar spectroscopic survey across the disk of M33. We present the stellar disk kinematics as a function of age to study the past and ongoing dynamical heating of M33. We measure line of sight velocities for ~4,500 disk stars. Using a subset, we divide the stars into broad age bins using Hubble Space Telescope and Canada-France-Hawaii-Telescope photometric catalogs: massive main sequence stars and helium burning stars (~80 Myr), intermediate mass asymptotic branch stars (~1 Gyr), and low mass red giant branch stars (~4 Gyr). We compare the stellar disk dynamics to that of the gas using existing HI, CO, and Halpha kinematics. We find that the disk of M33 has relatively low velocity dispersion (~16 km/s), and unlike in the Milky Way and Andromeda galaxies, there is no strong trend in velocity dispersion as a function of stellar age. The youngest disk stars are as dynamically hot as the oldest disk stars and are dynamically hotter than predicted by most M33 like low mass simulated analogs in Illustris. The velocity dispersion of the young stars is highly structured, with the large velocity dispersion fairly localized. The cause of this high velocity dispersion is not evident from the observations and simulated analogs presented here., Comment: 27 pages, 15 figures, 6 tables

We measure homogeneous distances to M31 and 38 associated stellar systems ($-$16.8$\le M_V \le$ $-$6.0), using time-series observations of RR Lyrae stars taken as part of the Hubble Space Telescope Treasury Survey of M31 Satellites. From $>700$ orbits of new/archival ACS imaging, we identify $>4700$ RR Lyrae stars and determine their periods and mean magnitudes to a typical precision of 0.01 days and 0.04 mag. Based on Period-Wesenheit-Metallicity relationships consistent with the Gaia eDR3 distance scale, we uniformly measure heliocentric and M31-centric distances to a typical precision of $\sim20$ kpc (3%) and $\sim10$ kpc (8%), respectively. We revise the 3D structure of the M31 galactic ecosystem and: (i) confirm a highly anisotropic spatial distribution such that $\sim80$% of M31's satellites reside on the near side of M31; this feature is not easily explained by observational effects; (ii) affirm the thin (rms $7-23$ kpc) planar "arc" of satellites that comprises roughly half (15) of the galaxies within 300 kpc from M31; (iii) reassess physical proximity of notable associations such as the NGC 147/185 pair and M33/AND XXII; and (iv) illustrate challenges in tip-of-the-red-giant branch distances for galaxies with $M_V > -9.5$, which can be biased by up to 35%. We emphasize the importance of RR Lyrae for accurate distances to faint galaxies that should be discovered by upcoming facilities (e.g., Rubin Observatory). We provide updated luminosities and sizes for our sample. Our distances will serve as the basis for future investigation of the star formation and orbital histories of the entire known M31 satellite system., 32 pages, 15 figures, accepted for publication on ApJ

We analyze the kinematics as a function of stellar age for Andromeda (M31) mass analogs from the IllustrisTNG cosmological simulation. We divide the star particles into four age groups: less than 1 Gyr, 1 to 5 Gyr, 5 to 10 Gyr, and greater 10 Gyr, and compare the kinematics of these groups to that of the neutral gas cells. We calculate rotation curves for the stellar and gaseous components of each analog from 2 kpc to 20 kpc from the center of mass. We find that the lag, or asymmetric drift (AD), between the gas rotation curve and the stellar rotation curve on average increases with stellar age. This finding is consistent with observational measurements of AD in the disk of the Andromeda galaxy. When the M31 analogs are separated into groups based on merger history, we find that there is a difference in the AD of the analogs that have had a 4:1 merger the last 4 Gyr, 8 Gyr, or 12 Gyr compared to analogs that have not experienced a 4:1 merger in the same time frame. The subset of analogs that have had a 4:1 merger within the last 4 Gyr are also similar to AD measurements of stars in the disk of M31, providing evidence that M31 may in fact have recently merged with a galaxy nearly one fourth of its mass. Further work using high resolution zoom in simulations is required to explore the contribution of internal heating to AD., 14 pages, 11 figures, accepted to MNRAS for publication July 20, 2020

BackgroundInterleukin-12 (IL-12) is a proinflammatory cytokine which bridges innate and adaptive immunity via induction of T helper 1 differentiation and promoting cytolytic activity of natural killer and T cells. IL-12 has demonstrated potent antitumor activity in syngeneic mouse models and promising anti-tumor efficacy in humans. However, development of IL-12 has been limited by severe systemic toxicities. To overcome toxicity and improve the therapeutic index of IL-12, we employed protein engineering to generate XTX301, a highly potent, half-life extended and masked IL-12. The masking domain of XTX301 is designed to pharmacologically inactivate IL-12 systemically and render an active IL-12 moiety upon cleavage by proteases that are enriched in the tumor microenvironment.MethodsWe conducted experiments to assess the binding, bioactivity, safety, and anti-tumor efficacy of XTX301. Binding interactions were measured via SPR, bioactivity was measured using STAT-4 phosphorylation in a reporter cell line, and IFN-g production was assessed in human PBMCs via ELISA. Anti-tumor efficacy and pharmacodynamics were assessed in MC38 and B16F10 syngeneic tumor mouse models using a XTX301 murine surrogate, mXTX301. Safety and pharmacokinetics of XTX301 were evaluated in non-human primates (NHP).ResultsXTX301 showed no detectable binding to the high affinity IL12RB2 demonstrating that the masking domain indeed prevents interaction with the receptor. Upon cleavage of the masking domain by relevant proteases, binding was observed and was comparable to XTX300 unmasked control. Likewise, restoration of activity upon proteolytic cleavage was observed in an IL-12-dependent reporter gene assay and in primary human PBMCs. Human IL-12 does not cross react with mouse IL-12 receptors; hence a murine surrogate (mXTX301) was created for in vivo anti-tumor efficacy evaluation. A single dose of mXTX301 demonstrated up to 90% tumor growth inhibition in an inflamed MC38 and non-inflamed B16F10 syngeneic mouse models. mXTX301 induced a ~3 fold increase in IFN-g in tumors compared to vehicle control and ~150 fold less peripheral IFN-g compared to mXTX300. XTX301 exhibits minimal elevation in liver enzymes and a 50-fold improvement in tolerability compared to XTX300, in a repeat dose NHP safety study.ConclusionsOur data demonstrates that both XTX301 and mXTX301 are inactive when in masked form and become activated upon proteolytic cleavage to exert bioactivity comparable to recombinant IL-12. For efficacy, mXTX301 demonstrated tumor selective activity in syngeneic mouse models. XTX301 was well tolerated in repeat dose NHP safety study. In conclusion, XTX301 has potential for exerting potent anti-tumor activity with a favorable tolerability profile.

International audience; Although currently available data indicate that Africa has the lowest usage of antimicrobials in animals in the world (adjusted by animal biomass), data show a high prevalence of antimicrobial resistance in foodborne pathogens isolated from animals and animal products. Apart from the lack of solid data on antimicrobial use in many countries in Africa, diff erent hypotheses could explain this situation. Qualitative interviews of farmers show a lack of knowledge and uninformed use of antimicrobials. Considering the development of animal farming to meet an increasing demand for proteins, this defi ciency represents a serious public health issue. We advocate for policies that consider the specifi c challenges faced by family farmers in Africa, to simultaneously improve access to veterinary drugs while strengthening the regulation of their use. We propose a global approach targeting the agri-food system, off ering innovative social and technical interventions on antimicrobial usage, adapted to family farmers.

A significant fraction of Milky Way (MW) satellites exhibit phase-space properties consistent with a coherent orbital plane. Using tailored N--body simulations of a spherical MW halo that recently captured a massive (1.8$\times 10^{11}$M$\odot$) LMC-like satellite, we identify the physical mechanisms that may enhance the clustering of orbital poles of objects orbiting the MW. The LMC deviates the orbital poles of MW dark matter (DM) particles from the present-day random distribution. Instead, the orbital poles of particles beyond $R\approx 50$kpc cluster near the present-day orbital pole of the LMC along a sinusoidal pattern across the sky. The density of orbital poles is enhanced near the LMC by a factor $\delta \rho_{max}$=30\%(50\%) with respect to underdense regions, and $\delta \rho_{iso}$=15\%(30\%) relative to the isolated MW simulation (no LMC) between 50-150 kpc (150-300 kpc). The clustering appears after the LMC's pericenter ($\approx$ 50 Myr ago, 49 kpc) and lasts for at least 1 Gyr. Clustering occurs because of three effects: 1) the LMC shifts the velocity and position of the central density of the MW's halo and disk; 2) the DM dynamical friction wake and collective response induced by the LMC changes the kinematics of particles; 3) observations of particles selected within spatial planes suffer from a bias, such that measuring orbital poles in a great circle in the sky enhances the probability of their orbital poles being clustered. This scenario should be ubiquitous in hosts that recently captured a massive satellite (at least $\approx$ 1:10 mass ratio), causing the clustering of orbital poles of halo tracers., Comment: Submitted to ApJ. 23 pages and 16 figures. Comments are welcome

We present the color-magnitude diagrams and star formation histories (SFHs) of seven ultra-faint dwarf galaxies: Horologium 1, Hydra 2, Phoenix 2, Reticulum 2, Sagittarius 2, Triangulum 2, and Tucana 2, derived from high-precision Hubble Space Telescope photometry. We find that the SFH of each galaxy is consistent with them having created at least 80% of the stellar mass by $z\sim6$. For all galaxies, we find quenching times older than 11.5 Gyr ago, compatible with the scenario in which reionization suppresses the star formation of small dark matter halos. However, our analysis also reveals some differences in the SFHs of candidate Magellanic Cloud satellites, i.e., galaxies that are likely satellites of the Large Magellanic Cloud and that entered the Milky Way potential only recently. Indeed, Magellanic satellites show quenching times about 600 Myr more recent with respect to those of other Milky Way satellites, on average, even though the respective timings are still compatible within the errors. This finding is consistent with theoretical models that suggest that satellites' SFHs may depend on their host environment at early times, although we caution that within the error bars all galaxies in our sample are consistent with being quenched at a single epoch., 7 pages, 3 figures, 2 tables. Accepted for publication in ApJL

We present deep Hubble Space Telescope (HST) photometry of the ultra-faint dwarf (UFD) galaxies Pegasus III (Peg III) and Pisces II (Psc II), two of the most distant satellites in the halo of the Milky Way (MW). We measure the structure of both galaxies, derive mass-to-light ratios with newly determined absolute magnitudes, and compare our findings to expectations from UFD-mass simulations. For Peg III, we find an elliptical half-light radius of $a_h{{=}}1.88^{+0.42}_{-0.33}$ arcminutes ($118^{+31}_{-30}$ pc) and $M_V{=}{-4.17}^{+0.19}_{-0.22}$; for Psc II, we measure $a_h{=}1.31^{+0.10}_{-0.09}$ arcminutes ($69\pm8$ pc) and $M_V{=}{-4.28}^{+0.19}_{-0.16}$. We do not find any morphological features that indicate a significant interaction between the two has occurred, despite their close separation of only $\sim$40 kpc. Using proper motions (PMs) from Gaia early Data Release 3, we investigate the possibility of any past association by integrating orbits for the two UFDs in a MW-only and a combined MW and Large Magellanic Cloud (LMC) potential. We find that including the gravitational influence of the LMC is crucial, even for these outer-halo satellites, and that a possible orbital history exists where Peg III and Psc II experienced a close ($\sim$10-20 kpc) passage about each other just over $\sim$1 Gyr ago, followed by a collective passage around the LMC ($\sim$30-60 kpc) just under $\sim$1 Gyr ago. Considering the large uncertainties on the PMs and the restrictive priors imposed to derive them, improved PM measurements for Peg III and Psc II will be necessary to clarify their relationship. This would add to the rare findings of confirmed pairs of satellites within the Local Group., Comment: 18 pages, 11 figures; submitted to ApJ

T cells expressing CD19-targeting chimeric antigen receptors (CARs) reveal high efficacy in the treatment of B cell malignancies. Here, we report that T cell receptor fusion constructs (TRuCs) comprising an antibody-based binding domain fused to T cell receptor (TCR) subunits can effectively reprogram an intact TCR complex to recognize tumor surface antigens. Unlike CARs, TRuCs become a functional component of the TCR complex. TRuC-T cells kill tumor cells as potently as second-generation CAR-T cells, but at significant lower cytokine release and despite the absence of an extra co-stimulatory domain. TRuC-T cells demonstrate potent anti-tumor activity in both liquid and solid tumor xenograft models. In several models, TRuC-T cells are more efficacious than respective CAR-T cells. TRuC-T cells are shown to engage the signaling capacity of the entire TCR complex in an HLA-independent manner., Supraphysiological T cell activation by chimeric antigen receptor (CAR) contributes to T cell exhaustion and adverse events in CAR T cell therapies. Here the authors engineer a synthetic antigen receptor that integrates into the endogenous TCR complex, preserving natural regulatory circuits and achieving improved performance in mouse tumor models.

Background: For infants with NEC treated non-surgically, there is no consensus for when to re-initiate enteral feeds after NEC. In a previous meta-analysis, earlier refeeding (4-7 days after diagnosis of NEC) suggested a decreased incidence of the combined adverse outcome (NEC recurrence or stricture) and possible other benefits. Based on this analysis, we implemented a standardized guideline for non-surgical NEC through a consensus survey of key stakeholders involved in the decision to start refeeding at our institution. We aimed to implement and monitor a multidisciplinary clinical consensus guideline to …

In today’s competitive market, inventory management is a difficult job for every business enterprises. Objects are getting deteriorate after some period of time and result into economic loss. Keeping this in mind, this inventory model is for perishable objects where the rate of deterioration is considered to be constant with a constant demand rate. To reflect the real-life situation, the model explores a two-level trade-credit policy, i.e. the supplier offers certain credit period to the retailer and simultaneously the retailer permits a permissible delay in payment to the consumers that helps to increase the demand. If the retailer clears its entire amount during the end of first credit period, then the retailer can utilize it to earn interest. Moreover, if the retailer fails to clear the account by the end of first period, then he/she is allowed to pay off the balance after first credit period or by the end of second credit period. Here, the financial loans can be reduced through constant demand and interest earned. This paper uses a classical optimization method and calculated several numerical examples to elaborate the model. Convexity of cost function is proved through graphs. The objective of the paper is to minimize the total cost with respect to the inventory cycle time. At last, sensitivity analysis is done to study the effects of varying inventory parameters on decision variable and optimal solution.

We use deep narrowband Ca H&K ($F395N$) imaging taken with the Hubble Space Telescope (HST) to construct the metallicity distribution function (MDF) of Local Group (LG) ultra-faint dwarf (UFD) galaxy Eridanus II (Eri II). When combined with archival $F475W$ and $F814W$ data, we measure metallicities for 60 resolved red giant branch stars as faint as $m_{F475W}\sim24$ mag, a factor of $\sim4$x more stars than current spectroscopic MDF determinations. We find that Eri II has a mean metallicity of [Fe/H]$=$-2.50$^{+0.07}_{-0.07}$ and a dispersion of $��_{\mbox{[Fe/H]}}=0.42^{+0.06}_{-0.06}$, which are consistent with spectroscopic MDFs, though more precisely constrained owing to a larger sample. We identify a handful of extremely metal-poor star candidates (EMP; [Fe/H] $< -3$) that are marginally bright enough for spectroscopic follow up. Eri II's MDF appears well-described by a leaky box chemical evolution model. We also compute an updated orbital history for Eri II using Gaia eDR3 proper motions, and find that it is likely on first infall into the Milky Way. Our findings suggest that Eri II underwent an evolutionary history similar to that of an isolated galaxy. Compared to MDFs for select cosmological simulations of similar mass galaxies, we find that Eri II has a lower fraction of stars with [Fe/H] $< -3$, though such comparisons should currently be treated with caution due to a paucity of simulations, selection effects, and known limitations of Ca H&K for EMPs. This study demonstrates the power of deep HST CaHK imaging for measuring the MDFs of UFDs., Resubmitted to ApJ with revisions following a positive referee report of the initial draft; 29 pages, 19 figures, and 3 tables, including appendix. Comments welcome!

Price is the most important factor influencing demand rate based on marketing and economic theory. Along with price, stock display is also a major factor, as displayed stocks may induce customers to purchase more due to its visibility. Moreover, the demand for perishable products depends on its freshness. However, relatively little devotion has been paid to the influence of expiration dates despite the fact that they are an important factor in consumers’ purchase decisions. As a result, we develop an inventory model for perishable products in which demand explicitly in a multivariate function of price, displayed stocks, and expiration dates. We then formulate the model by determining the optimal selling price to maximize the total profit by using classical optimization method with the necessary condition given by Kuhn-Tucker. Furthermore, we discuss the optimal decisions under two scenarios: upper bound of profit and lower bound of profit by taking holding cost as a function of upper and lower bound respectively. Finally, a numerical example is demonstrated along with sensitivity analysis to describe the impact of inventory parameters on the optimal decisions.