Enhanced radiation shielding efficiency of polystyrene nanocomposites with tailored lead oxide nanoparticles.

In this study, we investigated a novel polymer nano-composite, PS-PbO, containing two distinct nano-sizes of lead oxide nanoparticles (PbO-A and PbO-B), in addition to the bulk size (PbO-K). These nanoparticles were embedded separately in a polystyrene (PS) matrix at different weight percentages (10%, 15%, 25%, and 35%) using roll mill mixing and compressing molding. Our evaluation focused on the radiation attenuation ability of PS-PbO and the effect of particle size, considering gamma-ray energies ranging from 0.06 to 1.3 MeV (from sources like 241Am, 133Ba, 137Cs, and 60Co). The linear attenuation coefficient (LAC) was determined by analyzing samples of the synthesized composite with different thicknesses. Then, various shielding parameters were calculated, including total molecular, atomic, and electronic cross-sections (σmol, σatm, σel), as well as the effective atomic number and the electron density (Zeff and Neff). Surprisingly, modifying PbO particle sizes had a significant impact on shielding efficiency. For instance, the composite with 25 wt% of the smallest PbO-B particles showed a 26.7% increase in LAC at 0.059 keV compared to the composite with 25 wt% of PbO-K (larger particles). Notably, the LAC peaked at low energy (0.059 keV), close to the K-edge of Pb, where interaction is directly proportional to Z4. With increasing PbO concentrations, the LAC of PS-PbO composites increased steadily. Additionally, as PbO concentration increased, the composite's effective atomic number Zeff and the electron density Neff increased, leading to a greater total Gamma-ray interaction cross-section. Furthermore, when comparing the Half-Value Layers of the novel nanocomposite to traditional lead shielding, a 70% reduction in mass was observed. Notably, the composite containing the smallest nano-size of PbO exhibited the highest radiation-shielding efficiency among all combinations and could therefore be used to create inexpensive and lightweight shields.

Coproporphyrin-I as a Selective OATP1B Biomarker Can Be Used to Delineate the Mechanisms of Complex Drug-Drug Interactions: Cedirogant Case Study.

Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus developed for the treatment of chronic plaque psoriasis. Cedirogant induces cytochrome P450 (CYP) 3A4 while inhibiting P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, and OATP1B3 in vitro. Static drug-drug interactions (DDIs) predictions suggested possible clinical induction of CYP3A4, and inhibition of P-gp, BCRP, and OATP1B1, leading to challenges in interpreting DDI studies between cedirogant and substrates of CYP3A, P-gp, BCRP, and OATP1B1/3. Here the effects of cedirogant on the pharmacokinetics of two statin drugs were investigated in healthy participants. Coproporphyrin-I (CP-I), a selective endogenous OATP1B biomarker, was used to assess the impact of cedirogant on OATP1B. Cedirogant (375 mg once daily) increased rosuvastatin maximum plasma concentration (Cmax) and area under the plasma concentration curve (AUCtau) by 141% and 55%, respectively when co-administered, whereas atorvastatin Cmax increased by 40% with no effect on its AUCtau compared with administration of rosuvastatin/atorvastatin alone. Cedirogant did not increase CP-I exposures, indicating no clinical OATP1B inhibition. The increased rosuvastatin exposure and minimal change in atorvastatin exposure with co-administration of cedirogant is attributed to BCRP inhibition and interplay between P-gp/BCRP inhibition and CYP3A induction, respectively. Correlation analysis with data from two investigational drugs (glecaprevir and flubentylosin) demonstrated that OATP1B1 R-value of > 1.5 and [Cmax,u]/[OATP1B1 IC50] of > 0.1 are associated with > 1.25-fold increase in CP-I Cmax ratio. This demonstrates the utility of CP-I in disentangling mechanisms underlying a complex DDI involving multiple transporters and enzymes and proposes refined criteria for static OATP1B inhibition predictions.

Venetoclax in biomarker-selected multiple myeloma patients: Impact of exposure on clinical efficacy and safety.

Venetoclax, a potent BCL-2 inhibitor, is currently under development for treatment of t(11;14) Multiple myeloma (MM). The objective of this research was to investigate the exposure-response relationships of venetoclax for a phase 1/2 study evaluating venetoclax monotherapy or in combination with dexamethasone in relapsed or refractory MM. A total of 117 patients receiving venetoclax at 300, 600, 800, 900, or 1200 mg were included in the analysis. The impact of venetoclax exposures on efficacy (objective response rate [ORR], progression-free survival [PFS] and overall survival [OS]) as well as safety (treatment-emergent adverse effects (grade ≥3) of neutropenia, infection, and any grade of serious treatment-emergent adverse effects) was evaluated. In the t(11;14)-positive subpopulation, venetoclax exposure relationships to PFS and OS indicated a trend of longer PFS and OS with higher exposures. Moreover, logistic regression analyses for clinical response (ORR and ≥VGPR rate) demonstrated a statistically significant (p < 0.05) relationship with exposure. Evaluation of the exposure-safety relationships demonstrated a lack of a relationship between venetoclax exposures (AUCavg ) and grade ≥3 infections, grade ≥3 neutropenia, grade ≥3 treatment-emergent adverse events or any grade serious treatment-emergent adverse events. These findings support further study of venetoclax at 800 mg QD dose in combination with dexamethasone in the t(11;14)-positive patient population where increased efficacy was observed without an increase in safety events.Clinical Trial: NCT01794520 registered 20 February 2013.

Phase 2 study of ibrutinib plus venetoclax in Japanese patients with relapsed/refractory mantle cell lymphoma.

BACKGROUND: Despite high response rates to initial therapy, most patients with mantle cell lymphoma (MCL) experience relapsed or refractory (R/R) disease. Here, we report the efficacy, safety, and pharmacokinetics of the Phase 2, single-arm M20-075 study (NCT04477486) of ibrutinib and venetoclax combination therapy in Japanese patients with R/R MCL. METHODS: Patients received 560 mg ibrutinib and 400 mg venetoclax (after a 5-week ramp-up from 20 mg) once daily for up to 104 weeks. Primary endpoint was complete response (CR) rate by independent review committee (IRC). Secondary endpoints included overall response rate (ORR), duration of response (DOR), undetectable minimal residual disease (uMRD) rate, progression-free survival (PFS), overall survival (OS), safety including dose-limiting toxicity (DLT) assessment in the first six patients, and pharmacokinetic parameters. Full analysis set (FAS) comprised all treated patients. Per protocol set (PPS) excluded treated patients with non-evaluable disease at baseline by IRC. RESULTS: Thirteen patients were treated (FAS n = 13; PPS, n = 12). Median age was 71 years, patients had a median of two prior treatments. After a median follow-up of 9.6 months, IRC-assessed CR rate and ORR were both 83% (PPS). All six MRD-evaluable patients had uMRD. Median DOR, PFS, and OS were unreached. The most common Grade ≥ 3 treatment-emergent adverse event (TEAE) was neutropenia (23%); 1 patient discontinued due to squamous cell carcinoma of the lung. No DLTs, tumor lysis syndrome, or deaths related to TEAEs were observed. CONCLUSION: Ibrutinib plus venetoclax exhibited high response rates and a well-tolerated safety profile in Japanese patients with R/R MCL.

Phase 1 study of selinexor in combination with salvage chemotherapy in Adults with relapsed or refractory Acute myeloid leukemia.

Selinexor, an oral inhibitor of the nuclear transport protein Exportin-1, shows promising single-agent activity in clinical trials of relapsed/refractory (R/R) acute myeloid leukemia (AML) and preclinical synergy with topoisomerase (topo) IIα inhibitors. We conducted a phase 1, dose-escalation study of selinexor with mitoxantrone, etoposide, and cytarabine (MEC) in 23 patients aged < 60 years with R/R AML. Due to dose-limiting hyponatremia in 2 patients on dose level 2 (selinexor 40 mg/m2), the maximum tolerated dose was 30 mg/m2. The most common grade ≥ 3 treatment-related non-hematologic toxicities were febrile neutropenia, catheter-related infections, diarrhea, hyponatremia, and sepsis. The overall response rate was 43% with 6 patients (26%) achieving complete remission (CR), 2 (9%) with CR with incomplete count recovery, and 2 (9%) with a morphologic leukemia-free state. Seven of 10 responders proceeded to allogeneic stem cell transplantation. The combination of selinexor with MEC is a feasibile treatment option for patients with R/R AML.

Towards better delineation of hydrothermal alterations via multi-sensor remote sensing and airborne geophysical data.

Integrating various tools in targeting mineral deposits increases the chance of adequate detection and characterization of mineralization zones. Selecting a convenient dataset is a key for a precise geological and hydrothermal alteration mapping. Remote sensing and airborne geophysical data have proven their efficiency as tools for reliable mineral exploration. Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), Advanced land imager (ALI), Landsat 8 (L8), and Sentinel 2 data are widely-used data among various types of remote sensing images in resolving lithological and hydrothermal alteration mapping over the last two decades. ASTER is a well-established satellite in geological remote sensing with detailed Short-wave infrared (SWIR) range compared to visible and near-infrared region (VNIR) that controls iron-associated alteration detection. On contrary, ALI has excellent coverage of the VNIR area (6 bands), but does not possess the potentiality of ASTER for the SWIR and thermal regions. Landsat 8 is widely used and highly recommended for lithological and hydrothermal alteration mapping. The higher spatial (up to 10 m) resolution of Sentinel 2 MSI has preserved its role in producing accurate geological mapping. Notwithstanding the foregoing, implementing the four datasets in a single study is time-consuming. Thus, an important question when commencing an exploration project for hydrothermal alterations-related mineralization (orogenic mineral deposits in the current research) is: which dataset should be adopted to fulfill proper and adequate outputs? Here the four widely recommended datasets (ASTER, ALI, L8, and sentinel 2) have been tested by applying the widely-accepted techniques (false color combinations, band ratios, directed principal component analysis, and constrained energy minimization) for geological and hydrothermal alteration mapping of Gabal El Rukham-Gabal Mueilha district, Egypt. The study area is covered mainly by Neoproterozoic heterogeneous collection of ophiolitic components, island arc assemblage, intruded by enormous granitic rocks. Additionally, airborne magnetic and radiometric data were applied and compared with the remote sensing investigations for deciphering the structural and hydrothermal alteration patterns within the study area. The results demonstrated a different extent from one sensor to another, highlighting their varied efficacy in detecting hydrothermal alterations (mainly hydroxyl-bearing alterations and iron oxides). Moreover, the analysis of airborne magnetic and radiometric data showed hydrothermal alteration zones that are consistent with the detected alteration pattern. The coincidence between high magnetic anomalies, high values of the K/eTh ratio, and the resultant alterations confirm the real alteration anomalies. Over and above that, the remote sensing results and airborne geophysical indications were verified with fieldwork and petrographic investigations, and strongly recommend combining ASTER and Sentinel 2 results in further investigations. Based on the outputs of the current research, we expect better hydrothermal alteration delineation by adopting the current findings as they sharply narrow the zones to be further investigated via costly geophysical and geochemical methods in mineral exploration projects.

Venetoclax Penetrates the Blood Brain Barrier: A Pharmacokinetic Analysis in Pediatric Leukemia Patients.

Infiltration of malignant cells into the central nervous system in hematological malignancies correlates with poor clinical outcomes. Investigations into the penetration of venetoclax into the central nervous system have been limited. We report venetoclax pharmacokinetics in plasma and cerebrospinal fluid samples from a Phase 1 study in pediatric patients with relapsed or refractory malignancies that demonstrate venetoclax ability to cross into the central nervous system. Venetoclax was detected in cerebrospinal fluid (CSF) samples, with concentrations ranging from < 0.1 to 26 ng/mL (mean, 3.6 ng/mL) and a plasma:CSF ratio ranging from 44 to 1559 (mean, 385). Plasma:CSF ratios were comparable among patients with AML and ALL and no clear trend was observed in the ratios over the course of treatment. Moreover, improvement in central nervous system (CNS) involvement status was observed in patients who had measurable concentrations of venetoclax in the CSF. CNS resolution was observed for up to six months while on treatment. These findings highlight the potential role of venetoclax and provide the opportunity to further investigate its utility in improving clinical outcomes for patients with CNS complications.

Gamma-ray attenuation parameters of HDPE filled with different nano-size and Bulk WO3.

High-density polyethylene (HDPE) was obtained through a compression molding technique, and incorporated with different filler weight fractions (0, 10, 15, 25, and 35%) of bulk WO3, and two different WO3 nanoparticle sizes (45 nm and 24 nm). The radiation attenuation ability of the new category of polymer composite HDPE/WO3 was evaluated using gamma-ray energies ranging from 59.53 up to 1332.5keV of four radioactive sources 241Am, 133Ba, 137Cs, and 60Co. The mass attenuation coefficients µm, the total molecular cross-section σmol, the effective atomic cross-section σatom, the total electronic cross-section σel, the effective atomic number Zeff, electron density Neff, the half value layer (HVL), the tenth value layer (TVL), and the relaxation length were investigated. The obtained results of the gamma-ray attenuation parameters exhibited an outstanding influence of the size and weight fraction of WO3 filler on the gamma-ray shielding ability of the HDPE composite. A significant improvement was detected at low gamma-ray energies. The HVL of the synthesized HDPE composites is compared with that of pure lead as a conventional shielding material. HDPE composite filled with the smaller size of WO3 nanoparticle shows good improvement in the attenuation parameters, which suggests promising applications in radiation protection and gamma-ray shielding.

Assessment of X-ray shielding properties of polystyrene incorporated with different nano-sizes of PbO.

PbO (lead oxide) particles with different sizes were incorporated into polystyrene (PS) with various weight fractions (0, 10, 15, 25, 35%). These novel PS/PbO nano-composites were produced by roll mill mixing and compressing molding techniques and then investigated for radiation attenuation of X-rays (N-series/ISO 4037) typically used in radiology. Properties of the PbO particles were studied by X-ray diffraction (XRD). Filler dispersion and elemental composition of the prepared nano-composites were characterized using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), revealing better filler distribution and fewer agglomerations with smaller PbO particle size. Linear and mass attenuation coefficients (µ and µm), total molecular and atomic cross-sections (σmol and σatm), as well as effective atomic number and electron density (Zeff and Neff), were calculated for the energy range N40 to N200. The influence of PbO weight percentage on the enhancement of the shielding parameters of the nano-composites was expected; however, the effect of PbO particle size was surprising. Linear and mass attenuation coefficients for PS/PbO composites increased gradually with increasing PbO concentrations, and composites with a small size of nanoparticles showed best performance. In addition, increasing PbO concentration raised the effective atomic number Zeff of the composite. Hence, the electron density Neff increased, which provided a higher total interaction cross-section of X-rays with the composites. Maximum radiation shielding was observed for PS/PbO(B). It is concluded that this material might be used in developping low-cost and lightweight X-ray shielding to be used in radiology.

Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet.

BACKGROUND AND OBJECTIVE: Venetoclax is an approved BCL-2 inhibitor, currently under evaluation in different hematological malignancies in adult and pediatric populations. Venetoclax is available as 10, 50, and 100 mg tablets. To provide an alternative to patients who find taking the commonly prescribed 100 mg tablet a challenge, the interchangeability of lower-strength tablets with the 100 mg tablet was investigated. Additionally, newly developed oral suspension powder formulations to facilitate dosing in pediatrics were evaluated. METHODS: Pharmacokinetic data from 80 healthy female participants from three phase I studies were utilized to evaluate the bioavailability of (1) 10 and 50 mg tablets relative to a 100 mg tablet; (2) 0.72 and 7.2% (drug to total weight) oral powder formulations relative to the 100 mg tablet; and (3) oral powder formulations administered using different vehicles (apple juice, apple sauce, and yogurt) relative to water under fed conditions. RESULTS: Bioavailability assessments at a 100 mg dose of venetoclax demonstrated bioequivalence across the 10, 50, and 100 mg tablet strengths. Oral powder formulations met the bioequivalence criteria (0.80-1.25) with respect to area under the concentration-time curve to time of the last measurable concentration (AUCt) and to infinite time (AUC∞) but exhibited a slightly lower maximum plasma concentration (Cmax). Exposure-response analyses were utilized to demonstrate that the lower Cmax observed with the powder formulations is not clinically meaningful. The delivery vehicles tested did not affect the bioavailability of venetoclax oral powder formulations. CONCLUSIONS: The smaller-sized tablets (10 and 50 mg) and the newly developed oral powder formulations of venetoclax can be used interchangeably with the 100 mg tablets to improve the patients' experience, while maintaining adequate exposure. CLINICAL TRIALS IDENTIFIERS: NCT01682616, 11 September 2012; NCT02005471, 9 December 2013; NCT02242942, 17 September 2014; NCT02203773, 30 July 2014; NCT02287233, 10 November 2014; NCT02993523, 15 December 2016; NCT03069352, 3 March 2017.

Comparison of demographic, clinical and laboratory characteristics between first and second COVID-19 waves in a secondary care hospital in Qatar: a retrospective study.

OBJECTIVE: To compare the patient profile and outcomes in Qatar during the first and second waves of the COVID-19 pandemic. SETTING: A retrospective observational study was conducted comparing the demographic, clinical and laboratory characteristics of patients with COVID-19 infection admitted to a secondary care hospital, during the first and second waves of the pandemic. PARTICIPANTS: 1039 patients from the first wave and 991 from the second wave who had pneumonia on chest X-ray and had a confirmed SARS-CoV-2 infection by a real-time PCR test of a nasopharyngeal swab were included. Patients with a normal chest X-ray and those who had a negative PCR test despite a positive COVID-19 antigen test were excluded. OUTCOME: Length of stay, need for mechanical ventilation, final disposition and mortality were the key outcomes studied RESULTS: Influenza like symptoms (18.5% in the first wave vs 36.1% in the second wave, p 0.001), cough (79.2% vs 87%, p<0.001) and dyspnoea (27.5% vs 38% p<0.001) were more common in the second wave. Second wave patients had significantly higher respiratory rate, lower peripheral oxygen saturation, needed more supplemental oxygen and had higher incidence of pulmonary embolism. More patients received hydroxychloroquine and antibiotics during the first wave and more received steroids, antivirals and interleukin-1 antagonist during the second wave. The second wave had a shorter length of stay (14.58±7.75 vs 12.61±6.16, p<0.001) and more patients were discharged home (22% vs 10%, p<0.001). CONCLUSIONS: Patients who presented during the second wave of COVID-19 pandemic appeared to be more ill clinically and based on their laboratory parameters. They required shorter hospitalisation and were more likely to be discharged home. This could represent greater expertise in handling such patients that was acquired during the first wave as well as use of more appropriate and combination therapies during the second wave.

The significance of nanoparticles in brain cancer diagnosis and treatment: modeling and simulation.

A numerical analysis of specific absorption rate (SAR) and temperature distributions in a realistic human head model is presented in this study. The key challenge is to rise cancer temperature to an optimal temperature without heating nearby healthy tissues. The model's uniqueness is that it captures the effect of nanoparticles on both brain cancer diagnosis and treatment. A realistic human head model with a cancerous brain segmented from 2D magnetic resonance imaging (MRI) gained from an actual patient using 3D Slicer, modeled, and simulated using CST-Microwave Studio, and illuminated by Archimedes spiral antenna. At frequencies of 2450 MHz and 915 MHz, the model simulated the absence and presence of various nanoparticles. The obtained results suggest that when using nanoparticles, it is possible to achieve sufficient energy deposition and temperature rise to therapeutic values (greater than 42 °C) in brain cancers using the proposed noninvasive hyperthermia system at 915 MHz frequency, especially for gold nanoparticles, without harming surrounding healthy tissue. Our research might pave the way for a clinical applicator prototype that can heat brain cancer.

Antisense oligonucleotides: absorption, distribution, metabolism, and excretion.

INTRODUCTION: Antisense oligonucleotides (ASOs) have emerged as a promising novel drug modality that aims to address unmet medical needs. A record of six ASO drugs have been approved since 2016, and more candidates are in clinical development. ASOs are the most advanced class within the RNA-based therapeutics field. AREAS COVERED: This review highlights the two major backbones that are currently used to build the most advanced ASO platforms - the phosphorodiamidate morpholino oligomers (PMOs) and the phosphorothioates (PSs). The absorption, distribution, metabolism, and excretion (ADME) properties of the PMO and PS platforms are discussed in detail. EXPERT OPINION: Understanding the ADME properties of existing ASOs can foster further improvement of this cutting-edge therapy, thereby enabling researchers to safely develop ASO drugs and enhancing their ability to innovate. ABBREVIATIONS: 2'-MOE, 2'-O-methoxyethyl; 2'PS, 2 modified PS; ADME, absorption, distribution, metabolism, and excretion; ASO, antisense oligonucleotide; AUC, area under the curve; BNA, bridged nucleic acid; CPP, cell-penetrating peptide; CMV, cytomegalovirus; CNS, central nervous system; CYP, cytochrome P; DDI, drug-drug interaction; DMD, Duchenne muscular dystrophy; FDA, Food and Drug Administration; GalNAc3, triantennary N-acetyl galactosamine; IT, intrathecal; IV, intravenous; LNA, locked nucleic acid; mRNA, messenger RNA; NA, not applicable; PBPK, physiologically based pharmacokinetics; PD, pharmacodynamic; PK, pharmacokinetic; PMO, phosphorodiamidate morpholino oligomer; PMOplus, PMOs with positionally specific positive molecular charges; PPMO, peptide-conjugated PMO; PS, phosphorothioate; SC, subcutaneous; siRNA, small-interfering RNA; SMA, spinal muscular atrophy.

Towards Precise Interpretation of Oil Transformers via Novel Combined Techniques Based on DGA and Partial Discharge Sensors.

Power transformers are considered important and expensive items in electrical power networks. In this regard, the early discovery of potential faults in transformers considering datasets collected from diverse sensors can guarantee the continuous operation of electrical systems. Indeed, the discontinuity of these transformers is expensive and can lead to excessive economic losses for the power utilities. Dissolved gas analysis (DGA), as well as partial discharge (PD) tests considering different intelligent sensors for the measurement process, are used as diagnostic techniques for detecting the oil insulation level. This paper includes two parts; the first part is about the integration among the diagnosis results of recognized dissolved gas analysis techniques, in this part, the proposed techniques are classified into four techniques. The integration between the different DGA techniques not only improves the oil fault condition monitoring but also overcomes the individual weakness, and this positive feature is proved by using 532 samples from the Egyptian Electricity Transmission Company (EETC). The second part overview the experimental setup for (66/11.86 kV-40 MVA) power transformer which exists in the Egyptian Electricity Transmission Company (EETC), the first section in this part analyzes the dissolved gases concentricity for many samples, and the second section illustrates the measurement of PD particularly in this case study. The results demonstrate that precise interpretation of oil transformers can be provided to system operators, thanks to the combination of the most appropriate techniques.

Approaches to handling missing or "problematic" pharmacology data: Pharmacokinetics.

Missing or erroneous information is a common problem in the analysis of pharmacokinetic (PK) data. This may present as missing or inaccurate dose level or dose time, drug concentrations below the analytical limit of quantification, missing sample times, or missing or incorrect covariate information. Several methods to handle problematic data have been evaluated, although no single, broad set of recommendations for commonly occurring errors has been published. In this tutorial, we review the existing literature and present the results of our simulation studies that evaluated common methods to handle known data errors to bridge the remaining gaps and expand on the existing knowledge. This tutorial is intended for any scientist analyzing a PK data set with missing or apparently erroneous data. The approaches described herein may also be useful for the analysis of nonclinical PK data.

Severe SARS-CoV-2 infection presenting with acute kidney injury and diabetic ketoacidosis complicated by pancreatitis in a 53-year man with hypertension.

Severe COVID-19 infection is associated with significant stress and marked immune response that can affect many organs and precipitate DKA, pancreatitis, and acute renal injury, which might be permanent.

Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma.

Combining venetoclax, a selective BCL2 inhibitor, with low-dose navitoclax, a BCL-XL/BCL2 inhibitor, may allow targeting of both BCL2 and BCL-XL without dose-limiting thrombocytopenia associated with navitoclax monotherapy. The safety and preliminary efficacy of venetoclax with low-dose navitoclax and chemotherapy was assessed in this phase I dose-escalation study (NCT03181126) in pediatric and adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia or lymphoblastic lymphoma. Forty-seven patients received treatment. A recommended phase II dose of 50 mg navitoclax for adults and 25 mg for patients <45 kg with 400 mg adult-equivalent venetoclax was identified. Delayed hematopoietic recovery was the primary safety finding. The complete remission rate was 60%, including responses in patients who had previously received hematopoietic cell transplantation or immunotherapy. Thirteen patients (28%) proceeded to transplantation or CAR T-cell therapy on study. Venetoclax with navitoclax and chemotherapy was well tolerated and had promising efficacy in this heavily pretreated patient population. SIGNIFICANCE: In this phase I study, venetoclax with low-dose navitoclax and chemotherapy was well tolerated and had promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. Responses were observed in patients across histologic and genomic subtypes and in those who failed available therapies including stem cell transplant.See related commentary by Larkin and Byrd, p. 1324.This article is highlighted in the In This Issue feature, p. 1307.

Polymeric composite materials for radiation shielding: a review.

The rising use of radioactive elements is increasing radioactive pollution and calling for advanced materials to protect individuals. For instance, polymers are promising due to their mechanical, electrical, thermal, and multifunctional properties. Moreover, composites made of polymers and high atomic number fillers should allow to obtain material with low-weight, good flexibility, and good processability. Here we review the synthesis of polymer materials for radiation protection, with focus on the role of the nanofillers. We discuss the effectivness of polymeric materials for the absorption of fast neutrons. We also present the recycling of polymers into composites.