Endowing a NAO Robot With Practical Social-Touch Perception.

Social touch is essential to everyday interactions, but current socially assistive robots have limited touch-perception capabilities. Rather than build entirely new robotic systems, we propose to augment existing rigid-bodied robots with an external touch-perception system. This practical approach can enable researchers and caregivers to continue to use robotic technology they have already purchased and learned about, but with a myriad of new social-touch interactions possible. This paper presents a low-cost, easy-to-build, soft tactile-perception system that we created for the NAO robot, as well as participants' feedback on touching this system. We installed four of our fabric-and-foam-based resistive sensors on the curved surfaces of a NAO's left arm, including its hand, lower arm, upper arm, and shoulder. Fifteen adults then performed five types of affective touch-communication gestures (hitting, poking, squeezing, stroking, and tickling) at two force intensities (gentle and energetic) on the four sensor locations; we share this dataset of four time-varying resistances, our sensor patterns, and a characterization of the sensors' physical performance. After training, a gesture-classification algorithm based on a random forest identified the correct combined touch gesture and force intensity on windows of held-out test data with an average accuracy of 74.1%, which is more than eight times better than chance. Participants rated the sensor-equipped arm as pleasant to touch and liked the robot's presence significantly more after touch interactions. Our promising results show that this type of tactile-perception system can detect necessary social-touch communication cues from users, can be tailored to a variety of robot body parts, and can provide HRI researchers with the tools needed to implement social touch in their own systems.

Self-assembly of an anion receptor with metal-dependent kinase inhibition and potent in vitro anti-cancer properties.

One topical area of supramolecular chemistry is the binding of anionic species but despite the importance of anions in diverse cellular processes and for cancer development, anion receptors or 'binders' have received little attention as potential anti-cancer therapeutics. Here we report self-assembling trimetallic cryptands (e.g. [L2(Metal)3]6+ where Metal = Cu2+, Zn2+ or Mn2+) which can encapsulate a range of anions and which show metal-dependent differences in chemical and biological reactivities. In cell studies, both [L2Cu3]6+ and [L2Zn3]6+ complexes are highly toxic to a range of human cancer cell lines and they show significant metal-dependent selective activity towards cancer cells compared to healthy, non-cancerous cells (by up to 2000-fold). The addition of different anions to the complexes (e.g. PO43-, SO42- or PhOPO32-) further alters activity and selectivity allowing the activity to be modulated via a self-assembly process. The activity is attributed to the ability to either bind or hydrolyse phosphate esters and mechanistic studies show differential and selective inhibition of multiple kinases by both [L2Cu3]6+ and [L2Zn3]6+ complexes but via different mechanisms.

A phase I pharmacokinetic and safety study of Paclitaxel Injection Concentrate for Nano-dispersion (PICN) alone and in combination with carboplatin in patients with advanced solid malignancies and biliary tract cancers.

PURPOSE: Paclitaxel injection concentrate for nano-dispersion (PICN) is a Cremophor-free, nanotechnology-driven paclitaxel formulation. This phase I study examined the safety, tolerability, pharmacokinetics and maximum tolerated dose (MTD) of PICN alone and in combination with carboplatin. Its early efficacy in unresectable biliary tract cancers (BTCs) was also evaluated. METHODS: This multi-center study comprised two parts. Part A contained a dose-escalation cohort following "3 + 3" design using PICN monotherapy in advanced solid tumors (Part A1); Part A2 dose-expansion cohort was then conducted in advanced BTCs due to observed efficacy in Part A1. Part B1 and B2 evaluated escalating dose of PICN with carboplatin in advanced solid tumors. PICN was administered as a 30 min-infusion every 3 weeks without pre-medications for hypersensitivity reactions. RESULTS: Thirty-six patients received PICN monotherapy in Part A and 21 received PICN plus carboplatin in Part B. The MTD of PICN was determined to be 295 mg/m2 both as a monotherapy and in combination with carboplatin at AUC 5. Dose-proportional exposure in paclitaxel Cmax and AUC was observed overdose range from 175 to 325 mg/m2 for PICN monotherapy and its combination with carboplatin. Carboplatin did not alter PICN exposure. Clinically significant toxicities mainly include neutropenia and peripheral neuropathy. PICN monotherapy yielded a response rate of 20% in unresectable BTCs. CONCLUSION: This study demonstrated the safety and stable pharmacokinetics of PICN as a monotherapy and in combination with carboplatin. Single-agent PICN showed promising antitumor activity in advanced BTCs, warranting further studies to investigate its role in gastrointestinal cancers.

Self-Assembled Anion-Binding Cryptand for the Selective Liquid-Liquid Extraction of Phosphate Anions.

The ligands L1 and L2 form trinuclear self-assembled complexes with Cu2+ (i.e. [(L1 )2 Cu3 ]6+ or [(L2 )2 Cu3 ]6+ ) both of which act as a host to a variety of anions. Inclusion of long aliphatic chains on these ligands allows the assemblies to extract anions from aqueous media into organic solvents. Phosphate can be removed from water efficiently and highly selectively, even in the presence of other anions.

Tooth-to-Implant-Supported Fixed Partial Denture: A Comprehensive Overview of Systematic Reviews.

OBJECTIVES: Tooth-to-implant-connected prostheses have been described as a possible treatment option for patients with long-span edentulous situations that were not conducive for placement of an adequate number of supporting implants. In this comprehensive overview of systematic reviews, the incidence of complications and the long-term survival rates of tooth-to-implant-supported fixed partial dentures (FPDs) were evaluated to determine whether it is a viable treatment. MATERIALS AND METHODS: A systematic search of 5 electronic databases was conducted for systematic reviews and meta-analyses of tooth-to-implant-supported FPDs up to January 2017. The articles were AMSTAR rated for methodological quality, and low-quality articles were eliminated. RESULTS: The initial search yielded 369 reviews in PubMed, 248 in Web of Science, 49 in EMBASE, 63 in Cochrane Library, and 27 in Google Scholar. After removal of duplicates and after full-text analysis, 5 were selected for the overview. CONCLUSIONS: Within the limitations of this overview, it was concluded that (1) the 10-year survival rates for tooth-to-implant FPDs were lower than the 5-year survival rates, (2) the tooth-to-implant FPDs' survival was lower than the individual abutment tooth or implant supporting it, (3) the biological and technical complications were more at 10 years compared with 5 years, and (4) the intrusion of the abutment teeth was more in the nonrigid connection FPDs than the rigid connection FPDs. Therefore, tooth-to-implant FPDs are a viable option but should be considered secondary to other available options with higher long-term survival rates and lower complications.

A ligand strand that displays anion-dependant reactivity with acetonitrile; formation of either a mononuclear complex or head-to-tail circular helicate.

The ligand L2,2 contains two bidentate domains separated by a 3,3-diamino-2,2'-biphenyl spacer unit and with Cu(ClO4)2 a mononuclear species is formed (e.g. [Cu(L2,2)]2+). Upon coordination with Cu(triflate)2 the ligand undergoes reaction with an acetonitrile solvent, producing a different ligand with unsymmetrical bidentate and tridentate domains (L2,3). This new ligand results in the formation of a tetranuclear head-to-tail circular helicate [Cu4(L2,3)4]8+ showing that in the presence of the triflate anion the ligand denticity is changed.

Self-Assembly of an Anion-Binding Cryptand for the Selective Encapsulation, Sequestration, and Precipitation of Phosphate from Aqueous Systems.

The self-assembled trimetallic species [L2 Cu3 ]6+ contains a cavity that acts as a host to many different anions. By using X-ray crystallography, ESI-MS, and UV/Vis spectroscopy we show that these anions are encapsulated both in the solid state and aqueous systems. Upon encapsulation, the anions Br- , I- , CO32- , SiF62- , IO63- , VO43- , WO42- , CrO42- , SO42- , AsO43- , and PO43- are all precipitated from aqueous solution and can be removed by filtration. Furthermore, the cavity can be tuned to be selective to either phosphate or sulfate anions by variation of the pH. Phosphate anions can be removed from water, even in the presence of other common anions, reducing the concentration from 1000 to <0.1 ppm and recovering approximately 99 % of the phosphate anions.

Dihydrogen phosphate-containing dinuclear double assemblies that demonstrate phosphate reactivity to the tetrafluoroborate anion.

The ligands L1 and L2 both form dinuclear assemblies with Cu(ii) and these react with dihydrogen phosphate so that the anion is incorporated within the assembly (e.g. [Cu2L2(H2PO4)]3+). However, in the presence of tetrafluoroborate anions the phosphate undergoes reaction with the anion forming [Cu3(L1)3(O3POBF3)]3+ and [Cu2(L2)2(O2P(OBF3)2)]+.

Ruthenium-Containing Linear Helicates and Mesocates with Tuneable p53-Selective Cytotoxicity in Colorectal Cancer Cells.

The ligands L1 and L2 both form separable dinuclear double-stranded helicate and mesocate complexes with RuII . In contrast to clinically approved platinates, the helicate isomer of [Ru2 (L1 )2 ]4+ was preferentially cytotoxic to isogenic cells (HCT116 p53-/- ), which lack the critical tumour suppressor gene. The mesocate isomer shows the reverse selectivity, with the achiral isomer being preferentially cytotoxic towards HCT116 p53+/+ . Other structurally similar RuII -containing dinuclear complexes showed very little cytotoxic activity. This study demonstrates that alterations in ligand or isomer can have profound effects on cytotoxicity towards cancer cells of different p53 status and suggests that selectivity can be "tuned" to either genotype. In the search for compounds that can target difficult-to-treat tumours that lack the p53 tumour suppressor gene, [Ru2 (L1 )2 ]4+ is a promising compound for further development.

Structural Strength Benefits Observed at the Hip of Premenarcheal Gymnasts Are Maintained Into Young Adulthood 10 Years After Retirement From the Sport.

PURPOSE: Premenarcheal female gymnasts have been consistently found to have greater bone mass and structural advantages. However, little is known about whether these structural advantages are maintained after the loading stimulus is removed. Therefore, the purpose of this study was to investigate the structural properties at the hip after long-term retirement from gymnastics. METHODS: Structural properties were derived from dual-energy X-ray absorptiometry scans using the hip structural analysis program for the same 24 gymnasts and 21 nongymnasts both in adolescence (8-15 y) and adulthood (22-30 y). Structural measures were obtained at the narrow neck, intertrochanter, and femoral shaft and included cross-sectional area, section modulus, and buckling ratio. Multivariate analysis of covariance was used to assess differences between groups in bone measures while controlling for size, age, maturity, and physical activity. RESULTS: Gymnasts were found to have structural advantages at the narrow neck in adolescence (16% greater cross-sectional area, 17% greater section modulus, and 25% lower buckling ratio) and 14 years later (13% greater cross-sectional area and 26% lower buckling ratio). Benefits were also found at the intertrochanter and femoral shaft sites in adolescence and adulthood. CONCLUSION: Ten years after retirement from gymnastics, former gymnasts' maintained significantly better hip bone structure than females who did not participate in gymnastics during growth.

Catalytic sp3 -sp3 Functionalisation of Sulfonamides: Late-Stage Modification of Drug-Like Molecules.

A new application of Pd-catalysed allylation is reported that enables the synthesis of a range of branched sp3 -functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd0 catalysts and base at room temperature, direct allylation was efficiently performed, yielding products that are analogues of structural motifs seen in biologically active small molecules. The reaction was performed under mild conditions and could be applied to nanomolar sigma-receptor binders, thus enabling a late-stage functionalisation and efficient expansion of drug-like chemical space.

Single-dose, open-label study of the differences in pharmacokinetics of colchicine in subjects with renal impairment, including end-stage renal disease.

BACKGROUND AND OBJECTIVE: The effect of renal impairment on colchicine pharmacokinetics in patients with chronic kidney disease (CKD) has not been studied previously. We evaluated the effect of renal impairment on colchicine pharmacokinetics in patients with CKD. METHODS: The pharmacokinetics and safety of a single, oral 0.6-mg dose of colchicine was evaluated in an open-label study in eight healthy subjects with normal renal function; eight subjects each with mild, moderate, or severe renal impairment; and eight subjects with end-stage renal disease (ESRD) who received a single dose prior to receiving, and again following, hemodialysis. RESULTS: Colchicine exposure was similar for subjects with normal renal function, mild impairment, or ESRD prior to and during hemodialysis (24.7-31.7 ng·h/mL), but was up to twofold higher in subjects with moderate or severe renal impairment (48.9 and 48.0 ng·h/mL, respectively). A very small amount of the colchicine dose (mean of 5.2 %) was recovered in dialysate. CONCLUSIONS: It appears that patients with mild or moderate renal impairment or those actively receiving hemodialysis do not show accumulation of colchicine, whereas those with severe renal impairment show a doubling of exposure. All patients with renal impairment taking colchicine should be closely monitored, especially as many patients taking colchicine often have other comorbidities and may be taking other medications.

Formation of a dimer of trinuclear helicates which encapsulates an array of six hydrogen-bonded anions.

The amine-containing ligand L, composed of two bidentate pyridyl-thiazole moieties linked by a 1,3-diaminophenylene unit, reacts with copper(II) ions to form a dinuclear double helicate [Cu2 L2 ](4+) . Reaction of [Cu2 L2 ](4+) with dihydrogen phosphate (0.5 equivalents) gives the unsaturated dinuclear double helicate [Cu2 L2 (OPO3 H2 )](3+) . [Cu2 L2 (OPO3 H2 )](3+) further reacts with another 0.5 equivalents of dihydrogen phosphate to give a trinuclear circular helicate which then self-assembles into a hexameric cluster [{Cu3 L3 (OPO3 H2 )3 }](26+) .

Are dosing adjustments required for colchicine in the elderly compared with younger patients?

INTRODUCTION: The objective of this study was to compare the relative bioavailability of the US Food and Drug Administration-approved formulation of colchicine after a single 0.6 mg dose in young (18-30 years of age) and elderly (≥60 years of age) healthy subjects to determine whether dosing adjustments are required in elderly patients. METHODS: A single-dose, single-drug, parallel-group study was performed in 20 young subjects with normal renal function (defined as creatinine clearance [CrCl] ≥80 mL/min) and 18 elderly subjects with normal or mild renal impairment (CrCl ≥50 mL/min) in otherwise good health. Blood samples were collected for up to 72 hours postdose and analyzed for colchicine using a validated liquid chromatography/tandem mass spectrometry method. Noncompartmental pharmacokinetic parameters were compared using analysis of variance methods. RESULTS: There were no statistically significant (P < 0.05) differences in mean colchicine pharmacokinetic parameters between young and elderly subjects, including peak plasma concentration (C(max)) (2.53 vs. 2.56 ng/mL), time to C(max) (1.25 vs. 1.25 hours), area under the plasma concentration-time curve to infinity (22.29 vs. 25.01 ng/h/mL), elimination half-life (25.4 vs. 30.1 hours), oral clearance (0.40 vs. 0.35 L/h/kg), and apparent volume of distribution (14.3 vs. 14.8 L/kg), respectively. CONCLUSION: The lack of any significant differences in colchicine pharmacokinetic parameters between young and elderly healthy subjects, with some of the latter including mild renal impairment, suggests that dose modification of colchicine may not be necessary in healthy elderly patients. However, when evaluating the use of colchicine dosing in an elderly patient, the confounding effect on overall exposure and safety from comorbid conditions, the use of concomitant medications, and the administration of multiple doses should be considered.

Former premenarcheal gymnasts exhibit site-specific skeletal benefits in adulthood after long-term retirement.

Young female gymnasts have greater bone strength compared to controls; although possibly due to selection into gymnastics, it is thought that their loading activity during growth increases their bone mass, influencing both bone geometry and architecture. If such bone mass and geometric adaptations are maintained, this may potentially decrease the risk of osteoporosis and risk of fracture later in life. However, there is limited evidence of the persisting benefit of gymnastic exercise during growth on adult bone geometric parameters. Therefore, the purpose of this study was to determine whether adult bone geometry, volumetric density, and estimated strength were greater in retired gymnasts compared to controls, 10 years after retirement from the sport. Bone geometric and densitometric parameters, measured by peripheral quantitative computed tomography (pQCT) at the radius and tibia, were compared between 25 retired female gymnasts and 22 controls, age range 22 to 30 years, by multivariate analysis of covariance (covariates: age, height, and muscle cross-sectional area). Retired gymnasts had significantly greater adjusted total and trabecular area (16%), total and trabecular bone mineral content (BMC) (18% and 22%, respectively), and estimated strength (21%) at the distal radius (p < 0.05) than controls. Adjusted total and cortical area and BMC, medullary area, and estimated strength were also significantly greater (13% to 46%) in retired gymnasts at the 30% and 65% radial shaft sites (p < 0.05). At the distal tibia, retired gymnasts had 12% to 13% greater total and trabecular BMC and volumetric bone mineral density as well as 21% greater estimated strength; total and cortical BMC and estimated strength were also greater at the tibial shaft (8%, 11%, and 10%, respectively) (p < 0.05). Former female gymnasts have significantly better geometric and densitometric properties, as well as estimated strength, at the radius and tibia 10 years after retirement from gymnastics compared to females who did not participate in gymnastics in childhood and adolescence.

Higher premenarcheal bone mass in elite gymnasts is maintained into young adulthood after long-term retirement from sport: a 14-year follow-up.

Sports that impact-load the skeleton during childhood and adolescence increase determinants of bone strength such as bone mineral content and density; however, it is unclear if this benefit is maintained after retirement from the sport. The purpose of this study was to assess whether the previously reported higher bone mass in a group of premenarcheal gymnasts was still apparent 10 years after the cessation of participation and withdrawal of the gymnastics loading stimulus. In 1995, 30 gymnasts 8 to 15 years of age were measured and compared with 30 age-matched nongymnasts. Twenty-five former gymnasts and 22 nongymnasts were measured again 14 years later (2009 to 2010). Gymnasts had been retired from gymnastics training and competition for an average of 10 years. Total body (TB), lumbar spine (LS), and femoral neck (FN) bone mineral content (BMC) was assessed at both measurement occasions by dual-energy X-ray absorptiometry (DXA). Multivariate analysis of covariance (MANCOVA) was used to compare former gymnasts' and nongymnasts' BMC while controlling for differences in body size and maturation (covariates: age, height, weight, and years from menarche [1995] or age at menarche [2009 to 2010]). Premenarcheal gymnasts (measured in 1995) had significantly greater size-adjusted TB, LS, and FN BMC (p < 0.05) (15%, 17%, and 12%, respectively) than nongymnasts. Ten years after retirement, gymnasts had maintained similar size-adjusted TB, LS, and FN BMC differences (p < 0.05) (13%, 19%, and 13%, respectively) when compared with nongymnasts. Bone mass benefits in premenarcheal gymnasts were still apparent even after long-term (10 years) removal of the gymnastics loading stimulus.

Bone mineral accrual from 8 to 30 years of age: an estimation of peak bone mass.

Bone area (BA) and bone mineral content (BMC) were measured from childhood to young adulthood at the total body (TB), lumbar spine (LS), total hip (TH), and femoral neck (FN). BA and BMC values were expressed as a percentage of young-adult values to determine if and when values reached a plateau. Data were aligned on biological ages [years from peak height velocity (PHV)] to control for maturity. TB BA increased significantly from -4 to +4 years from PHV, with TB BMC reaching a plateau, on average, 2 years later at +6 years from PHV (equates to 18 and 20 years of age in girls and boys, respectively). LS BA increased significantly from -4 years from PHV to +3 years from PHV, whereas LS BMC increased until +4 from PHV. FN BA increased between -4 and +1 years from PHV, with FN BMC reaching a plateau, on average, 1 year later at +2 years from PHV. In the circumpubertal years (-2 to +2 years from PHV): 39% of the young-adult BMC was accrued at the TB in both males and females; 43% and 46% was accrued in males and females at the LS and TH, respectively; 33% (males and females) was accrued at the FN. In summary, we provide strong evidence that BA plateaus 1 to 2 years earlier than BMC. Depending on the skeletal site, peak bone mass occurs by the end of the second or early in the third decade of life. The data substantiate the importance of the circumpubertal years for accruing bone mineral.

Effect of maturational timing on bone mineral content accrual from childhood to adulthood: evidence from 15 years of longitudinal data.

A higher bone mass may reduce the risk of osteoporosis and fractures. The role of maturational timing for optimizing bone mass is controversial due to the lack of prospective evidence from childhood to adulthood. The purpose of this study was to examine the long term relationship between the onset of maturation and bone mineral content (BMC) development. Two hundred thirty individuals (109 males and 121 females) from the Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS) were classified into maturity groups based on age of peak height velocity. BMC was serially assessed using dual energy X-ray absorptiometry (DXA). Multilevel models were constructed to examine the independent development of BMC by maturity group. When age, body size, and body composition were controlled early maturing females had on average 3-4%, 62.2 ± 16.8g (p<0.05), more total body BMC than their average maturing peers by 20 years of age. In contrast, late maturing females had 50.7 ± 15.6g less total body BMC. No maturational effects were found at either the lumbar spine or femoral neck (p>0.05) in females. There were no significant differences in BMC development at any site among male maturational groups (p>0.05). In this group of healthy participants, there appears to be a sex-dependent effect on the relationship between maturational timing and total body BMC development. Early, average and late maturing males displayed similar BMC development. Late maturing females had compromised BMC accrual compared to their early and average maturing peers.

Conjunctival concentrations of a new ophthalmic solution formulation of moxifloxacin 0.5% in cataract surgery patients.

PURPOSE: To compare the conjunctival concentrations of moxifloxacin after instillation of a single drop of moxifloxacin ophthalmic solution, 0.5% (Moxi) or a new 0.5% ophthalmic solution formulation (MAF) containing a retention-enhancing agent in patients undergoing cataract surgery. METHODS: This was a randomized, double-masked, parallel-group study. One hundred thirty patients scheduled for routine phacoemulsification and intraocular lens implantation were randomized to both treatment and post-dose sample collection time points. A single topical drop of Moxi or MAF was instilled in the study eye. At the designated time (0.25, 0.5, 1, 3, or 5 h post-dose), 2 conjunctival biopsy samples were obtained (N = 11-13 per treatment condition). Concentrations of moxifloxacin were determined using a validated ultra-performance liquid chromatography method. Moxifloxacin exposure [maximum mean moxifloxacin concentrations (C(max)) and area under the concentration-time curve (AUC)] was estimated from the observed concentration-time data. RESULTS: The conjunctival moxifloxacin C(max), 43.8 µg/g, for MAF was achieved at 0.25 h. This was 1.8-fold higher than the C(max) for Moxi (24.1 µg/g), which was reached at 0.5 h post-dose. MAF AUC(0-3) was significantly greater than the AUC(0-3) of Moxi [50.5 (µg·h)/g vs. 27.1 (µg·h)/g; P < 0.05]. The conjunctival moxifloxacin C(max) for MAF was 337- to 730-fold greater than the reported minimum inhibitory concentration (MIC(90)) values for Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. The C(max):MIC(90) ratios for Moxi ranged from 185 to 402. Conjunctival AUC(0-24):MIC(90) ratios ranged from 777 to 1,683 for MAF and from 625 to 1,355 for Moxi. CONCLUSIONS: The new MAF ophthalmic formulation of moxifloxacin provided higher peak levels of moxifloxacin in the conjunctiva tissue, and larger total tissue exposure than the current, commercially available formulation. The superior penetration of MAF observed in this study could translate into greater eradication of bacteria.

The effect of aquatic exercise and education on lowering fall risk in older adults with hip osteoarthritis.

OBJECTIVE: To evaluate the effect of aquatic exercise and education on fall risk factors in older adults with hip osteoarthritis (OA). METHOD: Seventy-nine adults, 65 years of age or older with hip OA and at least 1 fall risk factor, were randomly assigned to 1 of 3 groups: aquatics and education (AE; aquatic exercise twice a wk with once-a-wk group education), aquatics only (A; 2 wk aquatic exercise) and control (C; usual activity). Balance, falls efficacy, dual-task function, functional performance (chair stands), and walking performance were measured pre- and postintervention or control period. RESULTS: There was a significant improvement in fall risk factors (full-factorial MANCOVA, baseline values as covariates; p = .038); AE improved in falls efficacy compared with C and in functional performance compared with A and C. CONCLUSION: The combination of aquatic exercise and education was effective in improving fall risk factors in older adults with arthritis.