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Philadelphia chromosome (Ph)-like acute lymphoblastic leukaemia (ALL) is a high-risk subtype with a gene expression profile similar to Ph-positive ALL, due to activation of tyrosine kinase signalling. To understand the clinical implications of Ph-like ALL, this single-centre retrospective study evaluates outcomes in 268 adults, largely Hispanic ALL patients treated between 2013 and 2024, with a subgroup analysis of 139 haematopoietic stem cell transplantation (HSCT) patients. ALL subtypes included 68 (25.4%) Ph-like, 89 (33.2%) Ph-positive, and 111 (41.4%) Ph-negative. Ph-like patients were the youngest age at diagnosis (p = 0.007), most likely to have refractory disease (p < 0.001), and least likely to achieve minimal residual disease (MRD) negativity after induction (p = 0.031). Relative to Ph-negative ALL, Ph-like achieved worse event-free survival (EFS) (HR = 1.66; 95% CI 1.12-2.46; p = 0.012), whereas Ph-positive had improved EFS (HR = 0.60; 95% CI 0.38-0.93; p = 0.024) and cumulative incidence of relapse (CIR) (HR = 0.59; 95% CI 0.35-0.99; p = 0.046). Within the transplant subgroup, Ph status did not impact disease-free survival (DFS), CIR, or overall survival (OS). However, patients who received blinatumomab within 1-year pre-HSCT had improved DFS (HR = 0.43; 95% CI 0.20-0.94; p = 0.034) and CIR (HR = 0.26; 95% CI 0.09-0.75; p = 0.13). In conclusion, our data suggest that Ph-like is less likely to respond to standard induction therapy and HSCT may result in similar survival outcomes to Ph-negative ALL.

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Introduction This study was designed to investigate the accuracy of clinical information provided by referring general dental practitioners (GDPs) following the introduction of a standardised referral form across Wales (the All Wales Universal Orthodontic Referral Form [AWUORF]) and to see whether the information given could be reliably used to screen the referrals.Aim To evaluate whether priority cases were being readily identified and whether inappropriate referrals could be minimised, thereby potentially reducing waiting lists.Method A service evaluation involving the retrospective study of 200 consecutive referrals to a specialist practice over a three-month period. A descriptive data analysis was undertaken.Results The GDPs had successfully identified the main complaint in 156 (78%) of the referrals. Of the 44 (22%) clinically inaccurate referrals, there was no impact on the patient in terms of referral pathway in 32 (16%) cases, but in the remaining 12 (6%), 5 (2.5%) cases were prioritised unnecessarily and the remaining 7 (3.5%) would have been seen more quickly had the GDP provided the relevant clinical information. The appropriateness of referral in terms of eligibility of the patient to receive NHS-funded orthodontic treatment was high with only 18 (9%) patients failing to meet the criteria.Conclusion The AWUORF successfully guides the GDP to make appropriate referrals and enables accurate triage in the majority of cases.

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The aim of the present study was to investigate whether a combination of platelet-rich plasma (PRP) and decalcified freeze-dried bone allograft (DFDBA) offers advantages over DFDBA and saline in infrabony defects. The objectives were to primarily evaluate changes in clinical attachment level (CAL) and secondarily changes in pocket depth (PD). A search was performed of electronic databases (Medline, PubMed, Embase, The Cochrane Central Register of Controlled Trials, and Web of Science), as well as hand searching and reference list searching. Only randomized, controlled trials published up until 30 March 2018 were included that had a follow-up period of at least 6 months. Four papers met the eligibility criteria and were critically appraised using the Consolidated Standards of Reporting Trials statement and put through the Cochrane Collaboration's tool for assessing risk of bias. In three of the four studies, clinically and significantly greater CAL gains and PD reductions were observed in patients who received PRP and DFDBA in comparison to those who received DFDBA and saline (P < 0.05). Methodological heterogeneity existed among the studies, especially in the preparation of PRP and the type of infrabony defect. This made it difficult to draw clear conclusions, but despite this, the studies could still be regarded, as significant as they showed a low risk of bias.

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This is the final report on the moss flora of the Bío-Bío Region (Región VIII) in south-central Chile where collections were made in 2001-2003. Reported in this paper are one species new to South America, four species new to Chile and 16 species new to the Region. With these new additions the total number of taxa in the Bío-Bío Region is 343, corresponding to 331 species and 12 infraspecific taxa. A complete checklist of the mosses for all the provinces in the Region is presented.

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Four p-type polymers were synthesized by modifying poly(bisdodecylquaterthiophene) (PQT12) to increase oxidizability by p-dopants. A sulfur atom is inserted between the thiophene rings and dodecyl chains, and/or 3,4-ethylenedioxy groups are appended to thiophene rings of PQT12. Doped with NOBF4, PQTS12 (with sulfur in side chains) shows a conductivity of 350 S cm-1, the highest reported nonionic conductivity among films made from dopant-polymer solutions. Doped with tetrafluorotetracyanoquinodimethane (F4TCNQ), PDTDE12 (with 3,4-ethylenedioxy groups on thiophene rings) shows a conductivity of 140 S cm-1. The converse combinations of polymer and dopant and formulations using a polymer with both the sulfur and ethylenedioxy modifications showed lower conductivities. The conductivities are stable in air without extrinsic ion contributions associated with PEDOT:PSS that cannot support sustained current or thermoelectric voltage. Efficient charge transfer, tighter π-π stacking, and strong intermolecular coupling are responsible for the conductivity. Values of nontransient Seebeck coefficient and conductivity agree with empirical modeling for materials with these levels of pure hole conductivity; the power factor compares favorably with prior p-type polymers made by the alternative process of immersion of polymer films into dopant solutions. Models and conductivities point to significant mobility increases induced by dopants on the order of 1-5 cm2 V-1 s-1, supported by field-effect transistor studies of slightly doped samples. The thermal conductivities were in the range of 0.2-0.5 W m-1 K-1, typical for conductive polymers. The results point to further enhancements that could be obtained by increasing doped polymer mobilities.

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The introduction of orthodontic therapists as a new group of dental care professionals (DCPs) requires that their training in specialist orthodontic practices has provision for monitoring the level of supervision and clinical care provided by the students. The University of Warwick Diploma in Orthodontic Therapy programme has developed a patient questionnaire with the aim of assessing the patient's perception of the student. The observational questionnaire was designed to cover the four General Dental Council (GDC) domains and learning outcomes for orthodontic therapists, such that patient response could potentially provide valuable feedback to support the training programme. Each of the 10 students had 30 questionnaires to complete. The questionnaire was anonymous and it was designed to be suitable for both young patients and their carers to complete in less than five minutes. The response rate was very high, with 291 of the 300 questionnaires being completed. The level of co-operation may have been partly due to the ease of completion of the questionnaire, but might suggest the willingness to provide supportive feedback for the students. This study provided formative feedback to students' educational and clinical development without impacting on a student's clinical activity and will be used to develop further assessment tools.

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An n-type pyromellitic diimide polymer composite with in situ microstructure growth of the common element compound SnCl2 reaches power factor of 50-100 µW m-1 K-2, the highest purely n-type polymer composite power factor yet reported. The composite has a gigantic Seebeck coefficient between -4000 and -5000 µV K-1, many times higher than other polymer composites.

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Leakage currents through the gate dielectric of thin film transistors remain a roadblock to the fabrication of organic field-effect transistors (OFETs) on ultrathin dielectrics. We report the first investigation of a self-assembled monolayer (SAM) dipole as an electrostatic barrier to reduce leakage currents in n-channel OFETs fabricated on a minimal, leaky ∼10 nm SiO2 dielectric on highly doped Si. The electric field associated with 1H,1H,2H,2H-perfluoro-octyltriethoxysilane (FOTS) and octyltriethoxysilane (OTS) dipolar chains affixed to the oxide surface of n-Si gave an order of magnitude decrease in gate leakage current and subthreshold leakage and a two order-of-magnitude increase in ON/OFF ratio for a naphthalenetetracarboxylic diimide (NTCDI) transistor. Identically fabricated devices on p-Si showed similarly reduced leakage and improved performance for oxides treated with the larger dipole FOTS monolayer, while OTS devices showed poorer transfer characteristics than those on bare oxide. Comparison of OFETs on both substrates revealed that relative device performance from OTS and FOTS treatments was dictated primarily by the organosilane chain and not the underlying siloxane-substrate bond. This conclusion is supported by the similar threshold voltages (VT) extrapolated for SAM-treated devices, which display positive relative VT shifts for FOTS on either substrate but opposite VT shifts for OTS treatment on n-Si and p-Si. Our results highlight the potential of dipolar SAMs as performance-enhancing layers for marginal quality dielectrics, broadening the material spectrum for low power, ultrathin organic electronics.

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Polycrystalline thin films of tellurium and organic semiconductor molecules are paired in heterostructured field-effect transistors built on Si/SiO2 substrates. While charge carrier mobilities can exceed 1 cm(2)/(V s), there is only a limited gate voltage range over which the current is modulated. We employ continuous and pulsed measurements on transistors to explore the influence of charge equilibration time on device behavior, finding that pulsed gating improves output characteristics. We also use surface potential measurements to investigate the interfacial vacuum level offset between materials, and we modify the interlayer potential profile by interposing statically charged dielectric layers on the silicon dioxide. We show that interfacial fields determine the gate voltage range over which Te shows a field effect in heterostructures with organic semiconductors and that modification of these fields can extend this range.

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We report the synthesis and characterization of two solution-processable pyromellitic diimide (PyDI)-acetylene-based conjugated homopolymers. Adjacent PyDI cores were connected with triple bond linkages by reacting 3,6-dibromo-N,N'-dialkyl pyromellitic diimides with bis(tributylstannyl)acetylene under Stille coupling conditions. Cyclic voltammetry revealed that these polymers have sufficient electron affinity to accept electrons. Absorption spectra revealed that one polymer, with a simple octyl chain, has greater intermolecular interaction or conjugation after forming a thin film, and that film exhibited electron transport in top-gate bottom-contact mode organic field-effect transistor (OFET) devices. X-ray diffraction (XRD) and atomic force microscopy (AFM) results show that the octyl polymer is amorphous on the bulk scale. The polymer exhibited electron mobility of about 2 × 10-4 cm2 V-1 s-1 with on/off ratio of 103 and is the simplest n-channel polymer yet reported. A 4-trifluoromethylphenethyl side chain did not result in measurable electron mobility. The octyl polymer exhibited negative Seebeck coefficient on the order of -40 µV/K in thermoelectric devices, further substantiating its n-channel activity. The demonstration of electron transport from such a simple polymer has opened a new path for obtaining n-channel semiconducting activity from polymer films.

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Elemental Te displays a wide variety of nanoscale morphologies of vapor-deposited films, depending on the substrate surface and temperature. These morphologies are correlated to field-effect mobilities in transistors made with Te as the lone semiconductor or from Te-organic multilayer semiconductors. Two examples of morphologies and transistor output characteristics, i.e., on a room temperature oxide and heated organic, are shown in the figure.

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OBJECTIVE: To examine incidence of mental health diagnoses during initial service of U.S. active duty military members and identify associations with deployment, attrition, and suicide. METHODS: A retrospective cohort of 576,502 service members (SMs) newly enlisted between 2003 and 2006 was identified. Data included medical encounter, deployment and attrition, and suicide. Multivariable logistic regression models examine the association between mental health diagnoses coded within the SMs' first 6 months of eligibility for health care benefits and deployment. Multivariable Cox proportional hazards models quantify the association between mental health diagnoses and attrition and suicide. RESULTS: The cumulative incidence of mental health diagnoses was approximately 9% at 6 months of service. Adjustment, depressive, and anxiety disorders were most common. Those with any mental health diagnosis during initial eligibility had increased risk of early attrition and were 77% less likely to deploy. Early mental health diagnoses were not statistically significantly associated with death by suicide. CONCLUSION: Mental health diagnoses during initial eligibility are common and associated with reduced odds of deployment and increased risk of early attrition. Policies designed to either retain or discharge SMs with a mental health diagnosis identified during initial training merit close examination in light of these findings.

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OBJECTIVES: The goal of this study was to investigate and identify risk factors for suicide among all active duty members of the US military during 2005 or 2007. METHODS: The study used a cross-sectional design and included the entire active duty military population. Study sample sizes were 2,064,183 for 2005 and 1,981,810 for 2007. Logistic regression models were used. RESULTS: Suicide rates for all services increased during this period. Mental health diagnoses, mental health visits, selective serotonin reuptake inhibitors (SSRIs), sleep prescriptions, reduction in rank, enlisted rank, and separation or divorce were associated with suicides. Deployments to Operation Enduring Freedom or Operation Iraqi Freedom were also associated with elevated odds ratios for all services in the 2007 population and for the Army in 2005. CONCLUSIONS: Additional research needs to address the increasing rates of suicide in active duty personnel. This should include careful evaluation of suicide prevention programs and the possible increase in risk associated with SSRIs and other mental health drugs, as well as the possible impact of shorter deployments, age, mental health diagnoses, and relationship problems.

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This report, prepared at the request of the Aerospace Medical Association (AsMA), reviews the present status of aeromedical regulation of depressive disorders and antidepressant medications, emphasizing the role of serotonin specific reuptake inhibitors (SSRIs). Aeromedical certifying authorities (CAs) generally prohibit pilots from flying with a diagnosed depressive disorder, and also prohibit flying while taking antidepressant medications, including SSRIs. Some CAs are reassessing these prohibitions, which are based on long aeromedical practices, in view of changing medical management of depressive disorders. Many pilots choose to fly while depressed, with or without medications, because of the long grounding periods mandated by current policies. Some SSRIs have very few aeromedically significant side effects. Modern psychiatric practice calls for long-term use of medication following clinical recovery from depressive disorders in order to prevent recurrent episodes. Given these and other factors, AsMA proposes that CAs remove the current absolute prohibitions against pilots flying while taking SSRIs, and adopt aeromedical protocols that include carefully controlled follow-up and review. AsMA urges all certificatory and regulatory authorities to consider immediately instituting a policy of using study groups to manage depressed aviators who require SSRI antidepressants. Protocols designed to aggressively manage the full spectrum of adverse possibilities related to SSRI use may enable the safe use of SSRIs in formerly depressed aviators who suffer no aeromedically significant side effects. In these closely managed cases of depressive disorders, special issuances or waivers for SSRI use are justified.

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Prolonged cardiac repolarization causes fatal cardiac arrhythmias. There is evidence that these contribute to sudden death associated with nocturnal hypoglycemia in young people with diabetes. We measured cardiac repolarization (QT interval [QTc] and QT dispersion [QTd]) during experimental hypoglycemia with and without beta-blockade and potassium infusion to establish possible mechanisms. Two groups of 10 nondiabetic men (study 1 and study 2) each underwent four hyperinsulinemic clamps: two euglycemic (5 mmol/l) and two hypoglycemic (5 mmol/l and 2.5 mmol/l for 60 min each). Study 1 was performed with and without potassium infusion to maintain normal concentrations and study 2 with and without beta-blockade (atenolol, 100 mg/day for 7 days). QTd was unchanged during euglycemia but increased during hypoglycemia (55 ms, P < 0.0001 vs. baseline), which was prevented by potassium (6 ms, P = 0.78). QTc increased significantly during hypoglycemia alone (67 ms, P < 0.0001) and during potassium replacement (46 ms, P = 0.02). In study 2, the increase in QTd during hypoglycemia (68 ms, P < 0.0001) was prevented by beta-blockade (3 ms, P = 0.88). The increase in QTc during hypoglycemia (55 ms, P < 0.0001) was prevented by beta-blockade (1 ms, P = 0.98). Our data indicate that hypoglycemia causes an acquired long QT syndrome. Sympathoadrenal stimulation is the main cause, through mechanisms that involve but are not limited to catecholamine-mediated hypokalemia. These abnormalities are prevented by selective beta-blockade.

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AIMS: Sudden death in young diabetic patients has been associated with nocturnal hypoglycaemia perhaps as a result of cardiac dysrhythmias following abnormal cardiac repolarization during hypoglycaemia. It was therefore important to compare the effect of soluble human insulin (HI) and a rapid-acting insulin analogue, insulin aspart (IAsp), on these aspects of cardiac function. METHODS: A total of 17 healthy males underwent identical hyperinsulinaemic hypoglycaemic clamps with blood glucose maintained at 5 mm for 30 min and reduced to 2.5 mm after an additional 30 min. Subjects received either HI or IAsp on two different occasions separated by 4-6 weeks. Regular measurements were made of two measures of cardiac repolarization, QT dispersion and QTc as well as of counter-regulatory hormones. RESULTS: The blood glucose lowering effect did not differ between IAsp and HI and the clearance rates were similar (HI mean +/- SD 1.24 +/- 0.12 l h(-1) kg(-1), IAsp mean +/- s.d. 1.22 +/- 0.32 l h(-1) kg(-1)). There were similar significant increases but no difference between treatments in QTc after hypoglycaemia induced by either IAsp or HI (480 +/- 37 ms vs 480 +/- 25 ms; NS). However, QT dispersion during hypoglycaemia was less pronounced with IAsp than with HI (92 +/- 36 ms vs 107 +/- 42 ms; P < 0.05). Plasma adrenaline increased significantly and similarly after both insulins (initial and final concentration, HI, 0.23 +/- 0.01 to 4.87 +/- 0.48 nm, P < 0.001, IAsp, 0.24 +/- 0.01 to 4.99 +/- 0.48 nm, P < 0.001). Serum potassium decreased significantly but by a similar amount between the groups (initial and final concentration, HI, 4.18 +/- 0.3 to 4.2 +/- 0.2 mm, P < 0.001, IAsp, 4.2 +/- 0.3 to 4.2 +/- 0.3 mm, P < 0.001). CONCLUSIONS: Soluble human insulin and insulin aspart had similar effects upon hypoglycaemia-induced alterations in cardiac repolarization, presumably because the effects of both regular insulin and insulin aspart on the sympathoadrenal response and potassium concentration were the same.

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Physicians frequently use serotonin reuptake inhibitors (SRIs) to treat a variety of psychiatric and medical conditions, many of which occur in aviators. SRIs are efficacious for treating acute conditions and may also prove useful for prophylaxis against recurrence through maintenance dosage. Aviators must meet standard safety criteria in order to use medications while performing flying duties, and must receive individual waivers as well. This article reviews the particular threats that serotonergic agents pose to aviation safety. Some SRIs may prove safer than others to use in the aviation environment, but such medications will require appropriate ground testing, and must provide aeromedically safe control of the symptoms for which they are prescribed.

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A total synthesis of FK-506 (1) is presented. The synthesis features a highly convergent approach utilizing a block coupling strategy. Top and bottom half sections of the molecule are coupled by addition of a vinyl cuprate with a spiroenone. The alpha-allyl aldol functionality is revealed by a reductive opening of the spiroenone system. The labile alpha,beta-diketoamide hemiketal portion of the molecule is prepared by a late stage generation and oxidation of a masked enediol. Top and bottom half segments are themselves derived by coupling of smaller subunits, resulting in a very convergent route.