An orthogonal C-H borylation--cross-coupling strategy for the preparation of tetrasubstituted "A2B2"-chrysene derivatives with tuneable photophysical properties.

The regioselective, orthogonal functionalisation of 4,10-dichlorochrysene enables the synthesis of a variety of 2,8,4,10-"A2B2"-tetrasubstituted chrysenes. Such compounds exhibit broadened UV-vis absorption spectra, decreased band gap and higher HOMO levels compared to the parent chrysene.

Heterostructures produced from nanosheet-based inks.

The new paradigm of heterostructures based on two-dimensional (2D) atomic crystals has already led to the observation of exciting physical phenomena and creation of novel devices. The possibility of combining layers of different 2D materials in one stack allows unprecedented control over the electronic and optical properties of the resulting material. Still, the current method of mechanical transfer of individual 2D crystals, though allowing exceptional control over the quality of such structures and interfaces, is not scalable. Here we show that such heterostructures can be assembled from chemically exfoliated 2D crystals, allowing for low-cost and scalable methods to be used in device fabrication.

The antibiofilm effects of Byotrol™ G32.

AIM: The purpose of this study was to evaluate a commercial antimicrobial formulation, Byotrol™ G32, as a potential coating for impeding biofilm formation on medical devices such as urinary catheters. METHODS AND RESULTS: The antimicrobial activity of Byotrol™ G32 and its individual constituents has been tested on planktonic and biofilm cultures of uropathogenic bacteria. The Byotrol™ G32 formulation was superior with MICs ranging from 3 µg ml(-1) to 15 µg ml(-1) for planktonic cultures and 3-20 µg ml(-1) for biofilms. Furthermore, Byotrol™ G32 was able to remove established biofilms and act as an antibiofilm surface coating. CONCLUSIONS: Byotrol™ G32 displays impressive antimicrobial activity both in suspension and as a coating. Pretreating medical devices with Byotrol™ G32 may significantly impede biofilm formation and prolong the lifetime of the device. SIGNIFICANCE AND IMPACT OF THE STUDY: Medical devices are indispensable in health care. They are, however, a predisposing factor in infection. This research has demonstrated that Byotrol™ G32 reduces bacterial growth and subsequent biofilm formation. Application of Byotrol™ G32 as a medical device coating could have a significant impact on the costs associated with device replacement and patient morbidity and mortality.

Poly(styrene oxide)-poly(ethylene oxide) block copolymers: From "classical" chemotherapeutic nanocarriers to active cell-response inducers.

Two poly(styrene oxide)-poly(ethylene oxide) (PSO-PEO) triblock copolymers with different chain lengths were analyzed as potential chemotherapeutic nanocarriers, and their ability to inhibit the P-glycoprotein (P-gp) efflux pump in a multidrug resistant (MDR) cell line were measured in order to establish possible cell-responses induced by the presence of the copolymer molecules. Thus, EO33SO14EO33 and EO38SO10EO38 polymeric micelles were tested regarding doxorubicin (DOXO) entrapment efficiency (solubilization test), physical stability (DLS), cytocompatibility (fibroblasts), release profiles at various pHs (in vitro tests), as well as P-gp inhibition and evasion and cytotoxicity of the DOXO-loaded micelles in an ovarian MDR NCI-ADR/RES cell line and in DOXO-sensitive MCF-7 cells. EO33SO14EO33 and EO38SO10EO38 formed spherical micelles (~13nm) at lower concentration than other copolymers under clinical evaluation (e.g. Pluronic®), exhibited 0.2% to 1.8% loading capacity, enhancing more than 60 times drug apparent solubility, and retained the cargo for long time. The copolymer unimers inhibited P-gp ATPase activity in a similar way as Pluronic P85, favoring DOXO accumulation in the resistant cell line, but not in the sensitive cell line. DOXO loaded in the micelles accumulated more slowly inside the cells, but caused greater cytotoxicity than free drug solutions in the NCI-ADR-RES cell line, which overexpressed P-gp. Hence, PSO-PEO block copolymers offer interesting features as new biological response modifiers to be used in the design of efficient nanocarriers for cancer chemotherapy.

Fabrication of planar organic nanotransistors using low temperature thermal nanoimprint lithography for chemical sensor applications.

A new fabrication process for the patterning of organic semiconductors at the nanoscale has been developed using low temperature thermal nanoimprint lithography and the details of this process are discussed. Novel planar nanotransistors have been fabricated and characterized from poly(3-hexylthiophene) (P3HT) and we demonstrate the feasibility of using such devices as highly sensitive chemical sensors.

MHC-based mate choice combines good genes and maintenance of MHC polymorphism.

Polymorphic genes of the major histocompatibility complex (MHC) are regarded as essential genes for individual fitness under conditions of natural and sexual selection. To test this hypothesis, we investigated the ultimate individual fitness trait--that of reproductive success. We used three-spined sticklebacks (Gasterosteus aculeatus) in seminatural enclosures, located in natural breeding areas where the experimental fish had been caught. During their reproductive period, fish were exposed continuously to their natural sympatric parasites. By genotyping almost 4000 eggs with nine microsatellites, we determined parenthood and inferred female mating decision. We found that with reference to their own MHC profile, female sticklebacks preferred to mate with males sharing an intermediate MHC diversity. In addition, males with a specific MHC haplotype were bigger and better at fighting a common parasite (Gyrodactylus sp.). This translated directly into Darwinian fitness since fish harbouring this specific MHC haplotype were more likely to be chosen and had a higher reproductive output. We conclude that females also based their mating decision on a specific MHC haplotype conferring resistance against a common parasite. This identifies and supports 'good genes'. We argue that such an interaction between host and parasite driving assortative mating is not only a prerequisite for negative frequency-dependent selection--a potential mechanism to explain the maintenance of MHC polymorphism, but also potentially speciation.

Calf-thigh sequential pneumatic compression compared with plantar venous pneumatic compression to prevent deep-vein thrombosis after non-lower extremity trauma.

OBJECTIVE: To compare the effectiveness of calf-thigh sequential pneumatic compression devices with the effectiveness of plantar venous intermittent pneumatic compression devices in prevention of venous thrombosis after major trauma. SUBJECTS AND METHODS: We evaluated 181 consecutive patients after major trauma without lower extremity injuries that precluded the use of pneumatic compression devices. We randomly assigned 149 patients to either calf-thigh sequential pneumatic compression or plantar venous pneumatic compression. After blinding the observers to the method of prophylaxis against deep-vein thrombosis, we performed bilateral compression ultrasonography on or before day 8 after randomization. RESULTS: Among 149 randomized patients, 62 who received calf-thigh sequential pneumatic compression and 62 who received plantar venous intermittent pneumatic compression devices completed the trial. Thirteen patients randomized to plantar venous intermittent pneumatic compression (21.0%) and 4 patients randomized to calf-thigh sequential pneumatic compression (6.5%) had deep-vein thrombosis (p = 0.009). Seven of 13 patients with deep-vein thrombosis after prophylaxis with plantar venous intermittent pneumatic compression had bilateral deep-vein thromboses, whereas all 4 patients with deep-vein thrombosis after prophylaxis with calf-thigh sequential pneumatic compression had unilateral deep-vein thrombosis. CONCLUSION: Calf-thigh sequential pneumatic compression prevents deep-vein thrombosis more effectively than plantar venous intermittent pneumatic compression after major trauma without lower extremity injuries.

Coancestry in apparently sporadic primary pulmonary hypertension.

OBJECTIVE: To examine sporadic cases of primary pulmonary hypertension of coancestry. DESIGN: An epidemiologic study of families of patients with primary pulmonary hypertension. SETTING: A university-affiliated referral population. PARTICIPANTS: Family members of 13 patients with primary pulmonary hypertension. MEASUREMENTS: Family pedigrees involving grandparents, parents, siblings, and children were supplemented by genealogic records. Coefficients of kinship (Ck) were calculated for the patients with primary pulmonary hypertension who demonstrated coancestry and compared with 500 sets of controls drawn at random from genealogic records. RESULTS: Two patients with sporadic primary pulmonary hypertension demonstrated coancestry. The great-great grandfather and great-great grandmother of one patient were the great-grandfather and great-grandmother of the other patient. No other cases of primary pulmonary hypertension were identified in these two families. The CK of the affected individuals (CK = 10.02 x 10(-5)) suggests strongly that the observed relationship did not occur by chance alone. Among 500 random sets of matched controls, only two sets yielded CK of 10.02 x 10(-5) or greater (p = 0.004). Coancestry could not be identified for the other five families of patients with sporadic primary pulmonary hypertension for whom genealogic records were available. CONCLUSIONS: The finding of coancestry in patients with sporadic primary pulmonary hypertension suggests that a genetic basis exists for some patients with apparently sporadic primary pulmonary hypertension. Familial primary pulmonary hypertension may be more common than previously recognized.

Physician-guided treatment compared with a heparin protocol for deep vein thrombosis.

BACKGROUND: Effective heparin therapy, defined by therapeutic prolongation of the activated partial thromboplastin time (APTT), decreases the risk of recurrent venous thromboembolism. Achieving therapeutic prolongation of the APTT within 24 hours of the start of heparin therapy has proved difficult. We hypothesized that a protocol that delivered high initial heparin infusions to patients without identifiable risk for bleeding complications would decrease the time to achieve a therapeutic anticoagulant effect without increasing the incidence of major bleeding complications. METHODS: To test this hypothesis, we studied concurrent patient cohorts. We defined a therapeutic anticoagulant effect (APTT > 55 seconds) to be an APTT more than 1.5 times the upper limit of normal. Twenty patients with acute symptomatic deep vein thrombosis received a 5000-U heparin bolus, followed by 1680 U/h (low risk to bleed) or 1240 U/h (high risk to bleed), adjusted by protocol-directed response to APTT results. Forty-eight patients with deep vein thrombosis were treated by their physicians. The Kaplan-Meier method was used to examine the proportion of patients who achieved an APTT greater than 55 seconds as a function of time. RESULTS: The two study cohorts did not differ with respect to age, weight, or risk factors for venous thromboembolism. Analysis of Kaplan-Meier curves showed that the heparin protocol decreased the time to achieve a therapeutic anticoagulant effect (P = .025). Ten (91%) of 11 patients (95% confidence interval, 59% to 100%) without risks to bleed who were treated by the heparin protocol and 29 (60%) of 48 patients (95% confidence interval, 45% to 74%) not treated by the protocol had an initial therapeutic APTT (P = .006). CONCLUSION: A protocol that delivers higher initial heparin infusions to patients without identifiable risks for bleeding decreases the time needed to achieve therapeutic prolongation of APTT, when compared with nonprotocol physician management.

The prevalence of early childhood autism: comparison of administrative and epidemiological studies.

The results of surveys and inquiries to identify autistic children, carried out in England and Wales, the U.S.A. and Denmark, are compared. Three studies, in each of which either a total population of children or a wide range of handicapped children was screened, using case-note inspection and interviews, all estimated the prevalence of the autistic syndrome to be between four and five children per 10,000 aged under 15 years. Inquiries that counted diagnosed cases only or that relied upon local authority records produced much lower prevalence rates for the autistic syndrome. The reasons for this are examined, and the implications for prevalence studies of handicapping conditions are discussed.

Idioventricular rhythm complicating acute myocardial infarction.

The incidence, natural history, prognosis, and electrocardiographic characteristics of idioventricular rhythm complicating acute myocardial infarction are described. It occurred as a transient arrhythmia nearly always within 24 hours of infarction in 61 (8%) of 737 patients, and was characterized by paroxysms of between 6 and 20 beats with widened bizarre QRS complexes at a rate of between 60 and 90 a minute. Most cases showed fusion beats and P waves dissociated from the QRS complexes, and in many cases idioventricular rhythm started during the slow phase of sinus arrhythmia. Though it usually occurred in patients with moderately severe transmural infarcts, the incidence of ventricular fibrillation and subsequent mortality was no greater than in patients with infarcts of equivalent severity who did not have idioventricular rhythm. It is concluded that this rhythm is a common and relatively benign arrhythmia complicating myocardial infarction, and that it should be distinguished from ventricular tachycardia.