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Cybersecurity attacks have been steadily increasing in the healthcare sector over the past decade. Health data is a valuable source of reliable and permanent personal information making it an attractive target. Institutions that have faced limited cybersecurity funding must now augment their approach to combat this threat. The Internet of Things (IoT) refers to the connection of physical operational devices to digital networks allowing for communication between devices. In the healthcare setting, this includes patient monitoring, diagnostics, and even robotic surgery devices. This increased connectivity increases the importance of agile and robust cybersecurity measures. A progressive approach must involve collaboration between information technology, clinical, and administrative leaders to be successful. Adequate protection of patient data and the integrity of digital infrastructure must be a priority mandate at the enterprise level.

Education is widely seen as a force for good, associated with hope and optimism about better individual and social futures. By contrast, and controversially, this paper argues that education and education policy in recent decades has been far from benign, as evidenced in the growing alienation of significant numbers of teachers and students and, crucially for our paper, in the growth of authoritarian models of schooling, involving �zero-tolerance�, �no excuses� disciplinary approaches. Against this background, and drawing on Hannah Arendt and the work of contemporary moral philosophers Elizabeth Minnich and Simona Forti, this paper diagnoses the nature and effects of school discipline policies in the neoliberal era, and in particular practices such as isolation, as a contemporary form of banal, or everyday, evil.�

IMPORTANCE: Finding a suitable fit in glasses for pediatric patients with congenital and acquired craniofacial abnormalities is difficult; consequently, these children are at high risk of vision loss secondary to refractive amblyopia as they often have poor adherence to daily glasses wearing. Custom 3-dimensional (3D)–printed glasses may have an improved design and fit, but access is limited by the availability of computed tomography and magnetic resonance imaging (MRI). OBJECTIVE: To describe a method for using a commercially available smartphone 3D surface imaging (3DSI) technique to capture facial anatomy as a basis for custom glasses design. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study analyzes data from a case series in a primary academic center with multiple referral centers throughout the United States. The evaluation included reported fit descriptions from patients with poor glasses adherence due to craniofacial abnormalities. MAIN OUTCOMES AND MEASURES: Key anatomic parameters for glasses fit (face width, distance from ear bridge to nasal bridge, distance from center of pupil to center of nasal bridge, distance from lateral to medial canthus, ear vertical offset, and nasal bridge width) were compared between scans. A 3DSI scan was considered successful if these key parameters could be determined and the difference in measurements was less than 5% between MRI and 3DSI. A second outcome measure included the fit of glasses designed by the 3DSI method as reported by the patient, parent, or guardian. RESULTS: Measurements of key parameters for glasses fit were similar across MRI and 3DSI scans with a mean (SD) difference of 1.47 (0.79) mm between parameters (range, 0.3-4.60 mm). Among 20 patients aged 1 to 17 years with craniofacial abnormalities, all achieved a successful fit (reporting daily glasses adherence without irritation) as judged by the patient, parent, or guardian. A mean of 1.7 revisions were made from initial prototype to final frame production using 3DSI technology. CONCLUSIONS AND RELEVANCE: This study demonstrated that smartphone-enabled 3DSI coupled with widely available 3D printing technology can produce custom frames with a successful fit for patients with craniofacial anomalies. This accessible and well-tolerated imaging process may have implications for adherence with glasses wearing among patients at risk of vision loss due to amblyopia.

This article highlights some of the key provisions employers should consider with employment agreements, and also emphasizes the restrictions and commitments that employment agreements should generally entail. ********** You are [...]

Objectives: To examine diarrhea-associated deaths among very low-birth-weight (VLBW) ([is less than]1500 g) infants and low- and normal-birth-weight (LNBW) ([is greater than or equal to] 1500 g) infants at birth and to identify specific interventions to prevent these deaths. Design: Retrospective analyses of linked infant and birth death data on diarrhea of all causes compiled by the National Center for Health Statistics, Centers for Disease Control and Prevention, Atlanta, Ga. Patients: Infants aged 27 days through 11 months who died with diarrhea. Setting: United States, 1991. Results: A majority (56%, n-143) of the 257 diarrhea-associated deaths reported among US infants in 1991 occurred among VLBW infants. Compared with LNBW infants, VLBW infants had a 100-fold greater diarrheal mortality (269 deaths per 100 000 live births for VLBW infants vs 2.8 deaths per 100 000 live births for LNBW infants), died at a younger age, and more often died in the hospital. Diarrhea-associated deaths among VLBW infants were strongly associated with prematurity and a low 1-minute Apgar score whereas African American race, less maternal education, and a low 1-minute Apgar score were associated with increased diarrheal mortality among LNBW infants. Conclusions: Infants of VLBW are at an increased risk for diarrheal deaths and new efforts are required to understand and improve the diagnosis of and therapy for diarrhea among these infants. For LNBW infants, diarrheal deaths remain a social problem and efforts need to focus on improved education and home-based rehydration therapy for children whose mothers fit the high-risk profile and who may lack adequate access to health care. Arch Pediatr Adolesc Med. 1998; 152:47-51, Very-low-birth-weight (VLBW) infants are at increased risk of developing potentially fatal diarrhea. Researchers analyzed data on all infants who died from diarrhea in the US in 1991. Of the 257 deaths from diarrhea, more than half occurred in VLBW infants. These infants had a 100-fold greater risk of fatal diarrhea compared to low-birth-weight infants. In VLBW infants, prematurity and a low Apgar score were linked to fatal diarrhea. Among low-birth-weight infants, African-American race and mothers with little education were linked to fatal diarrhea.

The article discusses two separate topics. The first topic is a month-long lockdown at the US Penitentiary in Leavenworth, Kansas, where prisoners reported limited access to showers and reduced meals. The second topic is a settlement agreement in Virginia, where the state agreed to pay $15,000 to a prisoner who was mauled by a DOC K-9. The article also briefly mentions a California law that extends involuntary commitment and detention to substance abusers. [Extracted from the article]

A study on how ligand backbone structure has an impact on selectivity, rate, and catalyst stability of hydroformylation catalysts was prompted by some longer-term stability issues being discovered for a phospholane-phosphite with a [−CH2O−] backbone. A series of phospholane-phosphite ligands were synthesized. Catalysts made in situfrom these ligands and [Rh(acac)(CO)2] were found to give iso-butanal selectivities up to 75% at temperatures between 75 and 105 °C: the latter being a benchmark for iso-selectivity in reactions conducted at industrially meaningful temperatures. A racemic rhodium complex of a bidentate phospholane-phosphite from a tropos-biphenol with an extended backbone showed unusually high stability at high temperatures, combined with even better iso-selectivity in propene hydroformylation relative to the original complex. A related ligand with an electron-withdrawing group maintained the unusually high stability and improved activity. Characterization of the precatalysts of type [RhH(CO)2(L)] was accomplished using in situHPIR spectroscopy and backed up by density functional theory calculations (B3PW91-D3 level) and by NMR studies; the latter showed that the variation of the backbone also had a pronounced impact on the precatalyst structure. A key finding is that it is now possible to prepare phospholane-phosphite ligands that deliver high iso-butanal selectivity and that show no signs of degradation after several days even above typical reaction temperatures. In one stability test, several kilograms of aldehydes were produced with TOF and selectivity being consistent over several days.

The town of Wenatchee, Washington, hugs the western confluence of the Columbia and Wenatchee Rivers, in the rain shadow of the Cascade Range. This favorable geographic position, with 300 days [...]

The article reports that a Florida county has agreed to pay $300,000 to settle a lawsuit over a jail suicide. The estate of Lukas MacKenzie Snelson, who committed suicide while in custody, filed a federal civil rights lawsuit against Escambia County Jail. The guards responsible for monitoring Snelson's welfare were found guilty of neglecting their duties. Critics argue that the county should have invested the money in alternatives to pretrial detention and addressing the root causes of crime, such as poverty and mental illness. The article also highlights concerns about the prison operator's track record and the challenges faced by detainees who are sent far away from their homes for trial. [Extracted from the article]

A federal civil rights lawsuit has been filed alleging that a Black Jamaican migrant held for federal Immigration and Customs Enforcement (ICE) at the Pike County Correctional Facility (PCCF) in Pennsylvania was subjected to racial slurs, choked, and pepper-sprayed while restrained in a chair. The incident occurred after the detainee used a homemade envelope to send a letter to his wife, which violated jail rules. The detainee suffered permanent injuries and was subjected to racial taunts and slurs throughout the ordeal. The lawsuit names the warden, six guards, the jail's healthcare provider, and two of its employees as defendants. [Extracted from the article]

The article discusses a recent ruling by the U.S. Court of Appeals for the Seventh Circuit regarding civil rights challenges to civil commitment. The court concluded that the principle laid out in Heck v. Humphrey applies, barring civil rights challenges to prison disciplinary actions unless the underlying commitment is terminated or shown to be invalid. The ruling extends this principle to challenges to civil commitment as a sexually violent person. The article also briefly mentions two Ohio prisoners and two guards who have been tried for assaults, resulting in one conviction and one acquittal. [Extracted from the article]

Catalyst-controlled regioselectivity in palladium-catalyzed carbonylation of alkenes has been a long-standing goal of homogeneous catalysis. In general, monophosphines do favor branched regioselectivity, but lead to poor enantioselectivity, while diphosphines give mainly linear products. Previously, we reported the simultaneous control of regio- and enantioselectivity in the hydroxy- and methoxycarbonylation of vinyl arenes with Pd complexes of the Phanephos ligand. Herein, we present a density functional theory study (B3PW91-D3 level of theory) of the catalytic cycle, supported by deuterium labeling studies, to understand its mechanism. Alkene coordination to a Pd-hydride species was identified as the origin of asymmetric induction and regioselectivity in both the parent Pd/Xylyl-Phanephos catalyst and electron-deficient analogue, and rationalized according to a quadrant-diagram representation. The mechanism by which the preferentially formed pro-(S) Pd-alkene complex can isomerize via rotation around the palladium–(C═C) bond was investigated. In the parent system, this process is in competition with the methanolysis step that leads to the ester product and is responsible for the overall loss of regioselectivity. On the other hand, the introduction of electron-withdrawing substituents on the catalyst framework results in the reduction of the methanolysis barriers, making the isomerization pathway energetically unfavorable and so leading simultaneously to high regiocontrol and good enantiomeric ratios.

ABSTRACTThe photographic work of Captain Linnaeus Tripe (ca. 1851–1860) falls in a transitional decade in which the albumen print began to supplant the salted paper print process. In the 1850s, a wide variety of albumen recipes led to a broad range of print sheens from matte to semi-glossy. These low sheen prints are more difficult to distinguish from salted paper prints. The presence of an albumen binder layer in these prints may not be as obvious as in later albumen prints, even under magnification. Instrumental analysis, such as infrared spectroscopy, can identify the presence of protein but cannot reliably differentiate between a binder layer and a subsequent coating. This paper discusses the visual and scientific analysis of prints created by Tripe. In addition, a set of standardized albumen print simulacra based on a recipe used by Tripe was prepared for comparison to his prints. Both groups of prints were investigated by visual examination, gloss measurement, and non-sampling instrumental analysis by ATR-FTIR, in addition to SEM analysis of the simulacra. The results of the research help to explain the material character of these prints and similar lightly albumenized prints of this period.

Making decisions on how best to treat cancer patients requires the integration of different data sets, including genomic profiles, tumour histopathology, radiological images, proteomic analysis and more. This wealth of biological information calls for novel strategies to integrate such information in a meaningful, predictive and experimentally verifiable way. In this Perspective we explain how executable computational models meet this need. Such models provide a means for comprehensive data integration, can be experimentally validated, are readily interpreted both biologically and clinically, and have the potential to predict effective therapies for different cancer types and subtypes. We explain what executable models are and how they can be used to represent the dynamic biological behaviours inherent in cancer, and demonstrate how such models, when coupled with automated reasoning, facilitate our understanding of the mechanisms by which oncogenic signalling pathways regulate tumours. We explore how executable models have impacted the field of cancer research and argue that extending them to represent a tumour in a specific patient (that is, an avatar) will pave the way for improved personalized treatments and precision medicine. Finally, we highlight some of the ongoing challenges in developing executable models and stress that effective cross-disciplinary efforts are key to forward progress in the field.

Alabama has been denied summary judgment in a prisoner's lawsuit over a knifepoint rape. The federal court declined to dismiss most of the claims made by the prisoner against officials with the state Department of Corrections. The court found evidence of deliberate indifference to prisoner-on-prisoner violence, serious medical needs, intentional infliction of emotional distress, and civil conspiracy. The court also noted that there were numerous reported incidents of assaults at the facility and evidence that senior DOC staff knew about staffing and assault problems but did nothing to correct them. [Extracted from the article]

The Eighth Circuit Court of Appeals affirmed an $800,000 jury award in a lawsuit against a contract doctor at an Arkansas jail. The detainee, Linda Warner, died of sepsis after her appendix ruptured while incarcerated. The court found no error in the lower court's judgment and credited the doctor with $500,000 from the settlement. The article also mentions a new justice center being constructed in Minnesota that aims to be more humane for detainees. [Extracted from the article]

Marked variation exists in the use of genomic data in tumour diagnosis, and optimal integration with conventional diagnostic technology remains uncertain despite several studies reporting improved diagnostic accuracy, selection for targeted treatments, and stratification for trials. Our aim was to assess the added value of molecular profiling in routine clinical practice and the impact on conventional and experimental treatments.

Wilms tumour is the most common childhood renal cancer and is genetically heterogeneous. While several Wilms tumour predisposition genes have been identified, there is strong evidence that further predisposition genes are likely to exist. Our study aim was to identify new predisposition genes for Wilms tumour.

A federal indictment has been handed down against Scott H. Jenkins, the Sheriff of Culpeper County in Virginia, for selling auxiliary deputy sheriff credentials. Jenkins is accused of accepting bribes totaling over $72,500 from local businessmen in exchange for issuing them badges, ID cards, guns, and body armor, and even helping one individual restore their gun rights. Jenkins, who is known for his far-right and anti-immigrant views, also founded the Make Virginia Great Again movement. He ran for reelection in November 2023 but lost to Tim Chilton. [Extracted from the article]

The hydrogenation of amides and other less electrophilic carbonyl derivatives with an N–C═O functionality requires significant improvements in scope and catalytic activity to be a genuinely useful reaction in industry. Here, we report the results of a study that examined whether such reactions are further disadvantaged by nitrogen-containing compounds such as aliphatic amines acting as inhibitors on the catalysts. In this case, an enantiomerically pure manganese catalyst previously established to be efficient in the hydrogenation of ketones, N-aryl-imines, and esters was used as a prototype of a manganese catalyst. This was accomplished by doping a model ester hydrogenation with various nitrogen-containing compounds and monitoring progress. Following from this, a protocol for the catalytic hydrogenation of amides and polyurethanes is described, including the catalytic hydrogenation of an axially chiral amide that resulted in low levels of kinetic resolution. The hypothesis of nitrogen-containing compounds acting as an inhibitor in the catalytic hydrogenation process has also been rationalized by using spectroscopy (high-pressure infrared (IR), nuclear magnetic resonance (NMR)) and mass spectrometry studies.

As the global demand for energy escalates, the increasing severity of environmental pollution underscores the urgent need for efficient development of hydrates—a promising, clean energy source with vast reserves. It is imperative to carry out reservoir stimulation on low-permeability hydrate reservoirs to enhance fluidity. In order to simulate the geometric morphology of complex fractures, based on the bifurcation fracture morphology in existing laboratory experiments, combined with embedded discrete fracture model and tree fractal theory, the multiphase and multi-component seepage mechanism, thermal conduction, thermal convection, and hydrate phase change in hydrate-bearing layers were comprehensively considered. Based on the TOUGH code, a TOUGH-EDFM module is developed to realize numerical simulation of three-dimensional four-phase four-component hydrate reservoir stimulation assisted depressurization development. We clarify the production capacity change characteristics, main methane dissociation zones, and gas-water migration trends after reservoir stimulation. The results indicate that in the multi-level branching fracture area, the increase in hydrate production in the primary fracture area of the reservoir is greater than that in the secondary fracture branching area. When the fractal scale factor is 0.56, the increase in production in the secondary branch fracture zone is 48% of that in the primary fracture zone. The cumulative gas production after the reservoir stimulation of Class III hydrate reservoirs can surpass that of the basic depressurization scheme by a remarkable 2.21 times, and the overall hydrate dissociation proportion has increased by 60%, indicating the ability of the reservoir to effectively utilize the energy within hydrate reservoirs, thereby significantly improving its depressurization development potential.

Solid electrolytes provide a route to the development of all-solid-state batteries that can potentially surpass the safety and performance of conventional liquid electrolyte-based devices. Sulfide solid electrolytes have received particular attention as a result of their high ionic conductivities. One of the main reasons for such high ionic conductivity is the apparently reduced grain boundary resistance of sulfide solid electrolytes compared to their oxide counterparts, but this is not fully established. Using two model electrolyte systems, Na3PS4and Na3PO4, we apply a novel microscale simulation approach to analyze ionic transport in polycrystalline materials with various grain volumes. For Na3PO4, high grain boundary resistance is found, with the Na-ion conductivity decreasing with decreasing grain volume. For Na3PS4, the overall influence of grain boundaries (GBs) is significantly reduced compared to the oxide. Detailed analysis reveals a minimal change in the local structures and Na-ion conduction mechanism between bulk and polycrystalline Na3PS4, whereas the change is far more substantial for Na3PO4, with evidence of over-coordination of Na ions at the GBs. Our microscale approach helps to explain the fundamentally different influences of GBs on ion transport in phosphate and thiophosphate solid electrolytes.

The field of pathology is developing rapidly, but is also greatly affected by staffing shortages. With the growing prevalence and complexity of diagnoses, Matthew Clarke and Tiffany M Graham explain how the new generation of pathologists can be trained and retained.

In the current competitive mortgage lending environment, lenders are continuing to search for revenue-generating channels to effectively reach the new generation of homebuyers. Today's homebuyers are accustomed to turning to [...]

Manganese catalysts derived from tridentate P,N,N ligands can be activated easily using weak bases for both ketone and ester hydrogenations. Kinetic studies indicate the ketone hydrogenations are 0th order in acetophenone, positive order in hydrogen and 1st order in the catalyst. This implies that the rate determining step of the reaction was the activation of hydrogen. New ligand systems with varying donor strength were studied and it was possible to make the hydrogen activation significantly more efficient; a catalyst displaying around a 3-fold increase in initial turn-over frequencies for the hydrogenation of acetophenone relative to the parent system was discovered as a result of these kinetic investigations. Ester hydrogenations and ketone transfer hydrogenation (isopropanol as reductant) are first order for both the substrate and catalysts. Kinetic studies also gained insight into catalyst stability and identified a working range in which the catalyst is stable throughout the catalytic reaction (and a larger working range where high yields can still be achieved). The new more active catalyst, combining an electron-rich phosphine with an electron-rich pyridine is capable of hydrogenating acetophenone using as little as 0.01 mol% catalyst at 65 °C. In all, protocols for reduction of 21 ketones and 15 esters are described.

The failure to develop effective therapies for pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) is in part due to their intrinsic heterogeneity. We aimed to quantitatively assess the extent to which this was present in these tumors through subclonal genomic analyses and to determine whether distinct tumor subpopulations may interact to promote tumorigenesis by generating subclonal patient-derived models in vitro and in vivo. Analysis of 142 sequenced tumors revealed multiple tumor subclones, spatially and temporally coexisting in a stable manner as observed by multiple sampling strategies. We isolated genotypically and phenotypically distinct subpopulations that we propose cooperate to enhance tumorigenicity and resistance to therapy. Inactivating mutations in the H4K20 histone methyltransferase KMT5B(SUV420H1), present in <1% of cells, abrogate DNA repair and confer increased invasion and migration on neighboring cells, in vitro and in vivo, through chemokine signaling and modulation of integrins. These data indicate that even rare tumor subpopulations may exert profound effects on tumorigenesis as a whole and may represent a new avenue for therapeutic development. Unraveling the mechanisms of subclonal diversity and communication in pGBM and DIPG will be an important step toward overcoming barriers to effective treatments.

The observation that BRCA1-and BRCA2-deficient cells are sensitive to inhibitors of poly(ADP–ribose) polymerase (PARP) has spurred the development of cancer therapies that use these inhibitors to target deficiencies in homologous recombination1. The cytotoxicity of PARP inhibitors depends on PARP trapping, the formation of non-covalent protein–DNA adducts composed of inhibited PARP1 bound to DNA lesions of unclear origins1–4. To address the nature of such lesions and the cellular consequences of PARP trapping, we undertook three CRISPR (clustered regularly interspersed palindromic repeats) screens to identify genes and pathways that mediate cellular resistance to olaparib, a clinically approved PARP inhibitor1. Here we present a high-confidence set of 73 genes, which when mutated cause increased sensitivity to PARP inhibitors. In addition to an expected enrichment for genes related to homologous recombination, we discovered that mutations in all three genes encoding ribonuclease H2 sensitized cells to PARP inhibition. We establish that the underlying cause of the PARP-inhibitor hypersensitivity of cells deficient in ribonuclease H2 is impaired ribonucleotide excision repair5. Embedded ribonucleotides, which are abundant in the genome of cells deficient in ribonucleotide excision repair, are substrates for cleavage by topoisomerase 1, resulting in PARP-trapping lesions that impede DNA replication and endanger genome integrity. We conclude that genomic ribonucleotides are a hitherto unappreciated source of PARP-trapping DNA lesions, and that the frequent deletion of RNASEH2Bin metastatic prostate cancer and chronic lymphocytic leukaemia could provide an opportunity to exploit these findings therapeutically. Mutations in all three genes encoding ribonuclease H2 sensitize cells to poly(ADP–ribose) polymerase inhibitors by compromising ribonucleotide excision repair.

The challenging reaction of unactivated ortho-substituted aromatic ethers with Grignard reagents has been found to be most effectively catalysed using nickel complexes of less sterically hindered ligands. Air stable, cheap, commercially available [NiCl2(PnBu3)2] stands out as an improved catalyst for this type of transformation. The improved results with this catalyst even extend to some couplings of a more activated substrate when examined at higher temperatures and at catalyst loadings down to 0.1 mol%. Unusual induction periods in these latter reactions have been related to the by-product magnesium salts acting as co-catalysts.

In this study, Ravichandran et al. induced extremely high rates of chromosome missegregation in yeast to determine how cells adapt to chromosomal instability (CIN) over time. They show that adaptation to CIN initially occurs through many different individual chromosomal aneuploidies, and their findings provide new insights into how cells adapt by obtaining specific complex aneuploid karyotypes in the presence of CIN.

Through exome sequencing, we identified six individuals with biallelic loss-of-function mutations in TRIP13. All six developed Wilms tumor. Constitutional mosaic aneuploidies, microcephaly, developmental delay and seizures, which are features of mosaic variegated aneuploidy (MVA) syndrome, were more variably present. Through functional studies, we show that TRIP13-mutant patient cells have no detectable TRIP13 and have substantial impairment of the spindle assembly checkpoint (SAC), leading to a high rate of chromosome missegregation. Accurate segregation, as well as SAC proficiency, is rescued by restoring TRIP13 function. Individuals with biallelic TRIP13 or BUB1B mutations have a high risk of embryonal tumors, and here we show that their cells display severe SAC impairment. MVA due to biallelic CEP57 mutations, or of unknown cause, is not associated with embryonal tumors and cells from these individuals show minimal SAC deficiency. These data provide insights into the complex relationships between aneuploidy and carcinogenesis.

The article discusses the addresses by the U.S. Secretary of State John Foster Dulles, in which a careful reading of his words is in order for what light they may throw on the current debate about national strategy. Ever since his sensational address before the Council on Foreign Relations, on January 12, 1954, the Secretary of State has been known as the Administration's leading advocate of "massive retaliation," a reputation that doubtless gives him the feeling of being a much misunderstood man. For to his critics Dulles has replied, from the first, that he wasn't talking about starting a war, but about "deterring" the other side from starting one.