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The protective barriers of the CNS present challenges during the treatment and monitoring of diseases. In particular, the blood brain barrier is a major hindrance to the delivery of imaging contrast agents and therapeutics to the brain. In this work, we use gas microbubble-assisted focused ultrasound to transiently open the blood brain barrier and locally deliver silica coated gold nanorods across the barrier. This particular nanoagent possesses a strong optical absorption which enables in vivo and ex vivo visualization of the delivered particles using ultrasound-guided photoacoustic imaging. The results of these studies demonstrate the potential of ultrasound-guided photoacoustics to image contrast agents delivered via microbubble-assisted focused ultrasound for longitudinal diagnostic imaging and for therapeutic monitoring of neurological diseases.

Sclerosing perineuromas are rare, benign peripheral nerve sheath tumors classically reported on the fingers and palms of young men. We present the case of a 12-year-old boy with a slow-growing nodule on his right knee. Excision was performed, and pathology was consistent with a sclerosing perineuroma. This case highlights an atypical presentation of a rare lesion and provides useful knowledge of the clinical scenarios in which sclerosing perineuromas should be included in a differential diagnosis.

Colorectal cancer is the third most common cancer and the third leading cause of cancer death in the United States. Growth factor–independent 1 (GFI1) is a zinc finger transcriptional repressor responsible for controlling secretory cell differentiation in the small intestine and colon. GFI1 plays a significant role in the development of human malignancies, including leukemia, lung cancer, and prostate cancer. However, the role of GFI1 in colorectal cancer progression is largely unknown. Our results demonstrate that RNA and protein expression of GFI1 are reduced in advanced-stage nonmucinous colorectal cancer. Subcutaneous tumor xenograft models demonstrated that the reexpression of GFI1 in 4 different human colorectal cancer cell lines inhibits tumor growth. To further investigate the role of Gfi1 in de novo colorectal tumorigenesis, we developed transgenic mice harboring a deletion of Gfi1 in the colon driven by CDX2-cre (Gfi1F/F; CDX2-cre) and crossed them with ApcMin/+ mice (ApcMin/+; Gfi1F/F; CDX2-cre). Loss of Gfi1 significantly increased the total number of colorectal adenomas compared with littermate controls with an APC mutation alone. Furthermore, we found that compound (ApcMin/+; Gfi1F/F; CDX2-cre) mice develop larger adenomas, invasive carcinoma, as well as hyperplastic lesions expressing the neuroendocrine marker chromogranin A, a feature that has not been previously described in APC-mutant tumors in mice. Collectively, these results demonstrate that GFI1 acts as a tumor suppressor gene in colorectal cancer, where deficiency of Gfi1 promotes malignancy in the colon. Implications: These findings reveal that GFI1 functions as a tumor suppressor gene in colorectal tumorigenesis.

Contains fulltext : 177598.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis. DESIGN: Observational cohort study. SETTING: Seven hundred and thirty ICUs in 84 countries. PATIENTS: All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission. MEASUREMENTS AND MAIN RESULTS: ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock. CONCLUSIONS: In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death.

Previous research has shown a significant association between psychopathy and substance abuse. To date, these associations have not been compared between men and women in forensic or correctional samples, an important topic in light of some empirical findings indicating that psychopathy manifests differently across gender in other contexts. The current study was designed to address this gap in the literature using archival data sets consisting of four large samples derived from forensic, correctional, and university settings, with different measures for psychopathy, alcohol, and substance use. As expected, psychopathy (particularly traits reflective of disinhibition/social deviance) was significantly and moderately correlated with alcohol and substance abuse in all four samples; however, with one minor exception, hierarchical regression analyses revealed no significant moderating effects of gender on these associations. These findings indicate that, although psychopathy may be manifested different...

CASE DESCRIPTION A 3-month-old sexually intact female chinchilla (Chinchilla lanigera) was examined for sudden onset of non–weight-bearing lameness of the right hind limb. CLINICAL FINDINGS On physical examination, the right pes was swollen. An open wound on the medial aspect of the metatarsal region exposed the second metatarsal bone, and the pes was displaced laterally. Radiographs of the right pes revealed oblique displaced fractures of the 4 metatarsal bones. TREATMENT AND OUTCOME Surgical treatment was elected, and enrofloxacin was administered prior to surgery. The protruding fragment of the second metatarsal bone was excised, and the third and fourth metatarsal bones were repaired with intramedullary pins and external skeletal fixation. The chinchilla was bearing weight on the affected limb 9 days after surgery with only mild lameness. The implants were removed 35 days after surgery when radiographs showed bony union of the third and fourth metatarsal bones and continued reduction of the fractures of the second and fifth metatarsal bones. Fifty-six days after surgery, the chinchilla was bearing full weight on the limb, and radiographs showed bony union of the third, fourth, and fifth metatarsal bones. CLINICAL RELEVANCE Findings suggested that intramedullary pinning combined with an epoxy resin external fixator may be an effective technique for metatarsal fracture repair in chinchillas. This method allowed physiologic positioning of the limb and functional hind limb use during fracture healing. Prospective studies of fracture healing in exotic small mammals are indicated.

Background Many reports in the medical literature describe patients with concurrent psoriasis and bullous pemphigoid (BP), but little is known about these patients. Objective: To characterize patients with concurrent BP and psoriasis and their disease course. Methods We performed a systematic review of the English literature for all documented cases of coexistent BP and psoriasis. Results Our search yielded 76 cases meeting inclusion criteria. The male-to-female ratio was 2.3:1. The average age of onset of BP was 65 years. Prior to BP eruption, 38% of the patients had acute worsening of their psoriasis. Ultraviolet radiation therapy was the most cited cause of BP outbreak (25%). The most used systemic treatments for BP outbreak were corticosteroids (45%) and methotrexate (18%). Conclusion Patients with BP and psoriasis are clinically distinct. Providers should be aware of the association between these diseases and be able to choose treatments that do not exacerbate either disease.

In situ, real-time characterization of surfaces exposed to plasmas is of great interest. Common chemical analysis methods such as x-ray photoelectron spectroscopy, Auger electron spectroscopy, and secondary ion mass spectroscopy cannot be used. Here, we discuss the use of glow discharge-optical emission spectroscopy for this purpose. A small coupon piece (aluminum coated with yttria in this study) was mounted on an rf-biased electrode and inserted into an opening in the reactor wall. Silicon or SiO2 substrates on a separately rf-biased electrode were etched in an inductively coupled plasma (ICP) of Cl2/Ar/O2 or C4F8/O2, respectively. Pulsed bias was applied to sputter the surface of the coupon piece in the wall at the edge of the ICP, either after etching in an Ar ICP or during etching in the Cl2/Ar/O2 ICP. Optical emission from the region above the coupon surface was collected and spectrally resolved. The difference in intensity between the coupon bias on and off conditions was used to determine what species were present on the surface. A quantification method for converting emission intensities into atomic composition depth profiles is presented.

A two-dimensional (r, z) numerical simulation of the discharge characteristics of an atmospheric pressure plasma jet (APPJ), with coaxial shielding gas, was performed. The helium working gas flowed in a central capillary tube, engulfing a needle electrode powered by 13.7 MHz radio frequency sinusoidal voltage. The N2 shielding gas flowed in the annular space of a coaxial tube. These gases emerged, in laminar flow, in a 78%N2-21%O2-1%Ar dry air ambient. The characteristics of the APPJ with shielding gas were compared to those of the APPJ without shielding gas. The nitrogen shielding gas hindered the diffusion of oxygen and argon from the ambient air into the helium jet. With the shielding gas present, more nitrogen penetrated into the helium core, causing a shorter plasma ‘plume’. The flow rates of the working and shielding gas, critically affected the gas temperature, and in turn the discharge characteristics. For a He flow of 2 standard liters per minute (slm), switching on the nitrogen shielding gas flow (at 4.5 slm) reduced the on-axis O2 and Ar mole fractions from 3.9 × 10 − 4 to 6.8 × 10 − 5 and from 1.9 × 10 − 5 to 3.3 × 10 − 6 , respectively, at an axial distance of 3 mm downstream of the nozzle. The radial profiles of the mole fractions of the ambient gases were monotonically and strongly decreasing towards the system axis, for short axial distances from the nozzle (∼1 mm), but became progressively flatter at longer distances from the nozzle (3 mm and 5 mm). Simulation predictions captured the salient features of experimental data of ambient species mole fractions in the plasma jet, and the 706 nm optical emission intensity profiles of the He 33S excited state.

The clouded leopard (Neofelis nebulosa) is classified as vulnerable on the International Union for the Conservation of Nature Red List of Threatened Species. However, diseases affecting this species across zoo populations are not well documented. The primary objective of this retrospective study was to identify common and significant causes of morbidity and mortality in captive-bred clouded leopards from European, Asian, and Australian institutions. Medical records from 44 zoological parks that held 271 clouded leopards from 1934 to 2017 were reviewed. Major causes of mortality in the dead leopards (n = 141) were respiratory disease (17%), maternal neglect and starvation (12%), generalized infectious disease (10%), digestive disease (10%), and trauma (10%). Six animals lived more than 20 yr and two were older than 22 yr. Diseases were recorded 344 times (average of two per leopard) in 166 living leopards. The body systems most frequently affected by disease in these 166 individuals were, in order of frequency, integumentary (prevalence = 21%), digestive (21%), respiratory (16%), musculoskeletal (12%), and urinary (10%) systems. Neoplasia (7%) was less frequent, followed by cardiovascular (5%), genital (3%), and viral (3%) disorders. Extensive, self-induced alopecia on the tail and dorsum was the most frequently reported dermatological disease, which is proposed to be called the “clouded leopard alopecia syndrome.” The most common neoplasm was pheochromocytoma (1%), followed by squamous cell carcinoma of the paw pads, pleural mesothelioma and multicentric lymphomas (

Remote plasma sources are widely used in applications such as chamber cleaning and flowable chemical vapor deposition. In these processes, it is desirable that the dissociation rate of feed gases be as high as possible and stable. Here, the authors present results on radical densities and gas dissociation fractions for a 400 kHz toroidal transformer-coupled plasma source (MKS Instruments), operating at a power density of 5–50 W/cm3 with feed gas mixtures of O2 or NF3 in Ar and pressures of 0.4 or 2.0 Torr. Radical densities and feed gas dissociation percentages in the plasma were measured by optical emission spectroscopy combined with Ar actinometry. In the plasma, O2 was about 60% dissociated in dilute O2 mixtures (10%–20%). Dissociation decreased with the increasing addition of O2, dropping to 10% dissociation for 90% O2 in the feed gas. NF3 was >95% dissociated for all NF3/Ar mixtures. Little or no dependence on the flow rate was found. Plasma products flow into an anodized Al downstream chamber that is probed by vacuum ultraviolet (VUV) absorption spectroscopy and line-of-sight molecular beam mass spectrometry. In the downstream chamber, O recombined on the walls to form O2 (detected by VUV O2 absorption). The measured downstream O/O2 ratio was a strongly increasing function of an increasing flow rate reproduced by a downstream global model with O wall recombination probability of γO between 0.001 and 0.002. NF3 does not reform in the downstream chamber, as verified by VUV absorption and mass spectrometry. No NF or NF2 was detected, and F mostly recombined to form F2 at the back of the downstream chamber, along with N2. The F2, F, and N2 product absolute number densities were consistent with the 3:1 F:N mass balance of the NF3 feed gas.

Etching of p-Si in 60 mTorr 10%Cl2/90%Ar Faraday-shielded inductively coupled high density plasmas was investigated under both ion-assisted etching (IAE) and photoassisted etching (PAE) conditions. Real-time etching rates and after-etching Si surface chemical compositions were obtained by laser interferometry and vacuum-transfer x-ray photoelectron spectroscopy (XPS), respectively. Precisely controlled ion energy distributions (IEDs) were generated by applying pulsed negative DC bias on the conductive sample stage. Above a 36 eV threshold at a total flow rate of 250 SCCM, the IAE rate increased with the square root of the ion energy. In contrast to the DC bias, etching under RF bias did not exhibit a threshold ion energy because of the wide IED. XPS spectra revealed that the surface layer under PAE conditions had a significantly lower chlorine content, composed of only SiCl. Under IAE conditions, however, silicon dangling bonds (Si•), SiCl2, and SiCl3 were found on the surface, in addition to SiCl, with a relative abundance of SiCl > SiCl2 > SiCl3. The absence of higher chlorides and Si• under PAE conditions suggested that vacuum ultraviolet photons and above threshold-energy ions interact with the surface very differently. By varying the duty cycle of the pulsed DC bias, it was found that the IAE rate scaled with the energetic ion dose, but only for low duty cycles. For higher duty cycles, the apparent IAE yield fell off with an increasing Cl coverage on the surface, as the duty cycle went up, which pointed to a negative synergy (antisynergism) between PAE and IAE as the explanation. This antisynergism was further supported by the observed decrease of the total etching rate with an increasing period of the pulsed DC bias. A plausible mechanism is that increasing the pulsing period causes more near-surface damage, creating more recombination centers that lead to a higher loss rate of electron-hole pairs through recombination, thereby reducing the PAE rate.Etching of p-Si in 60 mTorr 10%Cl2/90%Ar Faraday-shielded inductively coupled high density plasmas was investigated under both ion-assisted etching (IAE) and photoassisted etching (PAE) conditions. Real-time etching rates and after-etching Si surface chemical compositions were obtained by laser interferometry and vacuum-transfer x-ray photoelectron spectroscopy (XPS), respectively. Precisely controlled ion energy distributions (IEDs) were generated by applying pulsed negative DC bias on the conductive sample stage. Above a 36 eV threshold at a total flow rate of 250 SCCM, the IAE rate increased with the square root of the ion energy. In contrast to the DC bias, etching under RF bias did not exhibit a threshold ion energy because of the wide IED. XPS spectra revealed that the surface layer under PAE conditions had a significantly lower chlorine content, composed of only SiCl. Under IAE conditions, however, silicon dangling bonds (Si•), SiCl2, and SiCl3 were found on the surface, in addition to SiCl, with a...

Infant protein intake has been associated with child growth, however, research on maternal protein intake during pregnancy is limited. Insulin-like growth factors (IGF) play a role in early fetal development and maternal protein intake may influence child body composition via IGF-1. The aim of this study was to investigate the association of maternal protein intake throughout pregnancy on cord blood IGF-1 and child body composition from birth to 5 years of age. Analysis was carried out on 570 mother–child dyads from the Randomised cOntrol trial of LOw glycaemic index diet study. Protein intake was recorded using 3-d food diaries in each trimester of pregnancy and protein intake per kg of maternal weight (g/d per kg) was calculated. Cord blood IGF-1 was measured at birth. Infant anthropometry was measured at birth, 6 months, 2 and 5 years of age. Mixed modelling, linear regression, and mediation analysis were carried out. Birth weight centiles were positively associated with early-pregnancy protein intake (g/d per kg), while weight centiles from 6 months to 5 years were negatively associated (B=−21·6, Pin utero effect on offspring body composition with a higher weight initially at birth but slower growth rates into childhood. Further research is needed to elucidate the exact mechanisms by which dietary protein modulates fetal growth.

Summary Background Elevated stearoyl-CoA desaturase 1 (SCD-1) activity showed associations with obesity in cross-sectional studies. In non-pregnant populations, nutrition regulates SCD-1 transcription and activity. Objective To investigate the longitudinal associations of maternal and fetal SCD-1 activity markers with infant anthropometry up to 2 years of age, and to explore how selected dietary intakes modulate SCD-1 activity in pregnancy. Methods As a secondary analysis from the ROLO intervention study, which was conducted in a population at risk for macrosomia, non-esterified fatty acids (NEFA) from maternal plasma at 13 and 28 weeks' gestation and in cord blood were measured via liquid-chromatography-mass-spectrometry. Fatty acid ratios 18:1/18:0 and 16:1/16:0 were used as markers for SCD-1 activity (‘desaturation indices’, DIs). Relationships of DIs with infant anthropometry up to 2 years of age and maternal dietary parameters during pregnancy were investigated using adjusted linear regression models and p-values correction for multiple testing. Results 18:1/18:0, but not 16:1/16:0, was associated with measures of infant anthropometry at birth (maternal and fetal markers) and up to 2 years of age (maternal markers only). Dietary intakes did not show strong associations with 18:1/18:0, but 16:1/16:0 was associated with absolute and relative dietary intakes. Conclusions In a population at risk for macrosomia, maternal SCD-1 activity measured via 18:1/18:0 was involved in the fetal programming of infant obesity, but could not be substantially modulated by short-term diet in pregnancy. Clinical trial registration ISRCTN Registration number: ISRCTN54392969 ( http://www.isrctn.com/ISRCTN54392969 ).

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in the United States, causing about 50,000 deaths each year. Growth Factor-Independent 1 (GFI1) is a critical zinc finger transcriptional repressor responsible for controlling secretory cell differentiation in the small intestine and colon. GFI1 plays a significant role in the development of human malignancies, including leukemia, lung cancer and prostate cancer. However, the role of GFI1 in CRC progression is largely unknown. Our results demonstrate that RNA and protein expression of GFI1 are reduced in advanced stages of non-mucinous CRC. Subcutaneous tumor models demonstrated that the re-expression of GFI1 in 4 different human CRC cell lines inhibits tumor growth by 25-60%. To further investigate the role of Gfi1 in de novo colorectal tumorigenesis, we developed transgenic mice harboring a deletion of Gfi1 in the distal intestine driven by the CDX2cre (Gfi1F/F; CDX2cre/+) and crossed them with ApcMin/+ mice (ApcMin/+; Gfi1F/F; CDX2cre/+). Loss of Gfi1 significantly increased the total number of colorectal adenomas compared to littermate controls with an APC mutation alone. Furthermore, we found that compound (ApcMin/+; Gfi1F/F; CDX2cre/+) mice develop both adenomas as well as carcinoid-like tumors expressing the neuroendocrine marker chromogranin A, a feature that has not been previously described in APC-mutant tumors in mice. Collectively, these results demonstrate that Gfi1 deficiency promotes colorectal tumorigenesis, and suggest that loss of Gfi1 may promote formation of carcinoid cancers of the large intestines.SignificanceThese findings reveal that GFI1 functions as a tumor suppressor gene in colorectal tumorigenesis.

Rigid bronchoscopy may be used to relieve acute airway obstruction following induction of anaesthesia and is a recommended option for management of the difficult airway. The ability of anaesthetists to perform rigid bronchoscopy has not been reported. We sought to explore the acquisition of procedural skill in rigid bronchoscopy by anaesthesiologists in a manikin. In a prospective interventional study, participants were asked to perform 40 rigid bronchoscopies in a TruCorp AirSim Advance airway manikin, configured to a randomised sequence of easy or difficult laryngoscopic grades to which the participants were blinded. The primary outcome was stabilisation (the attempt after which no further reduction in procedural time occurred). Dental injury and oesophageal intubation were also recorded. Forty anaesthesiologists and 40 unskilled controls (without laryngoscopic skills) participated. In the easy model, stabilisation occurred at attempt 8 in the anaesthesiology group and 10 in the unskilled controls. In the difficult model, stabilisation occurred at attempt 10 in both groups. Dental injury was less common in the anaesthesiology group. The proportion of participants achieving procedural competency did not differ between groups in either the easy (35/40 vs. 30/40) or difficult model (32/40 vs. 25/40). This study shows that the technical skill of rigid bronchoscopy can be acquired within 10 repetitions in a manikin model. As procedural competence and complication frequency vary with the laryngoscopic grade of the model, both easy and difficult configurations should be used for training. Advanced laryngoscopic skills are not required prior to training in this technique.

Inductively coupled plasmas (ICPs) are widely used for etching in semiconductor device fabrication. The use of pulse power - alternating periods of power-on and power-off at pulse repetition frequencies (PRF) of up to 10s kHz - is becoming more common. The process often uses highly attaching halogen gases in which the electrons are nearly fully convert to negative ions during the power-off period. The low electron density at the start of the next pulse can produce instabilities, E-H transitions and ignition delays. To address these issues, a low-level power could be maintained to limit the minimum plasma density. The remaining electrons can then seed the next plasma ignition, thereby reducing the ignition delay and enhancing the plasma stability.

White matter tissue properties are known to correlate with performance across domains ranging from reading to math, to executive function. Here, we use a longitudinal intervention design to examine experience-dependent growth in reading skills and white matter in grade school-aged, struggling readers. Diffusion MRI data were collected at regular intervals during an 8-week, intensive reading intervention. These measurements reveal large-scale changes throughout a collection of white matter tracts, in concert with growth in reading skill. Additionally, we identify tracts whose properties predict reading skill but remain fixed throughout the intervention, suggesting that some anatomical properties stably predict the ease with which a child learns to read, while others dynamically reflect the effects of experience. These results underscore the importance of considering recent experience when interpreting cross-sectional anatomy–behavior correlations. Widespread changes throughout the white matter may be a hallmark of rapid plasticity associated with an intensive learning experience., White matter properties correlate with cognitive performance in a number of domains. Here the authors show that altering a child’s educational environment though a targeted intervention program induces rapid, large-scale changes in the white matter, and that these changes track the learning process.

Protein aggregation is a central feature of most neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Protein aggregates are closely associated with neuropathology in these diseases, although the exact mechanism by which aberrant protein aggregation disrupts normal cellular homeostasis is not known. Emerging data provide strong support for the hypothesis that pathogenic aggregates in AD, PD, HD, and ALS have many similarities to prions, which are protein-only infectious agents responsible for the transmissible spongiform encephalopathies. Prions self-replicate by templating the conversion of natively-folded versions of the same protein, causing spread of the aggregation phenotype. How prions and prion-like proteins in AD, PD, HD, and ALS move from one cell to another is currently an area of intense investigation. Here, a Drosophila melanogaster model that permits monitoring of prion-like, cell-to-cell transmission of mutant huntingtin (Htt) aggregates associated with HD is described. This model takes advantage of powerful tools for manipulating transgene expression in many different Drosophila tissues and utilizes a fluorescently-tagged cytoplasmic protein to directly report prion-like transfer of mutant Htt aggregates. Importantly, the approach we describe here can be used to identify novel genes and pathways that mediate spreading of protein aggregates between diverse cell types in vivo. Information gained from these studies will expand the limited understanding of the pathogenic mechanisms that underlie neurodegenerative diseases and reveal new opportunities for therapeutic intervention.

This chapter introduces the concepts of blank art more thoroughly while addressing the two key themes of Violence and Power that are discussed throughout the book. The author introduces the importance of understanding how Violence functions in blank art as a form of commentary on political actions taken by the Reagan/Bush administration in the 1980s as well as by members of the powerful, capitalist elite in the United States at the same time. The author then discusses the idea of Power as a concept force in culture, in the economic, political, and philosophical sense. Encompassing both concepts in Marxist and Postmodern theoretical discourse, the author then situates them in the realm of media and art. Using blank works to identify the ways in which artists and the public can harness the influence of media for themselves, the author offers the beginnings of a powerful message for the ways in which popular art can be used as a tool for positive political control.

This chapter offers an analysis of John McNaughton’s Henry: Portrait of a Serial Killer (1986), a precise and exemplary piece of blank cinema. It demonstrates the blank movement’s use of the serial killer figure as an especially powerful tool for social and political criticism. It is a cinematic work of phenomenological interrogation of a serial murderer.

This chapter looks at the legacy of blank fiction and cinema, exploring the echoes of the blank arts of the 1980s into the 1990s and early 2000s. The authors look at how the form of blank fiction echoes throughout recent socially conscious works and illuminate specific elements of the blank style, including limited plot, a focus on characters whose motives are unexplained, the incorporation and manipulation of signs of traditional power, and an emphasis on emptiness.

This chapter situates the book historically, offering an in depth look at Ronald Reagan’s rise to power and his reelection in 1984. Examining the economic, political, and cultural climate of the time, the author examines what was happening in the United States at the time that the works of blank fiction and cinema became popular.

Chapter seven addresses the presence of the serial killer in blank art. The author argues that this horror trope serial serves as a way for some artists to interrogate the force of institutionalized racism in 1980s America through its popular media. In blank fiction and cinema, for example, there is an emphasis on the “unexamined” whiteness of characters and a focus on the deviance of such characters’ actions and notions of privilege from the popular, traditional American moral ideology. The film Manhunter is explored, as a more traditional example of a serial killer cinema film, to hold in contrast to the two examples of blank works explored in chapters eight and nine.

While literature is clear on the relationship between results control, incentives, and extrinsic motivation, there is little evidence on how (or whether) management controls are associated with intrinsic motivation. The purpose of this study is to provide evidence on this relationship since intrinsic motivation is critical to the persistence of long-term performance effects and desirable behaviors, such as learning and creativity. Using survey data from 196 employees, we examine whether personnel and action controls positively influence intrinsic motivation by increasing individuals’ perceptions of autonomy. We find that both of the personnel controls, feedback and training, and one of the action controls, visual management, influence performance through perceptions of autonomy and the extent to which respondents find work activities to be challenge motivating. The results show that the second type of action control, standard operating procedures, is not associated with autonomy but instead has a direct positive association with the extent to which respondents find their work activities enjoyment motivating, and, in turn, with performance. We also find that our results depend on length of tenure with the organization.

To explore the association between vitamin B12 deficiency and dementia in patients at high risk for vitamin B12 deficiency.Chart review.Emergency, critical care/ trauma, neurology, medicine, and rehabilitation units of two hospitals in Southwestern Ontario, Canada.Adult patients (n = 666) admitted from 2010 to 2012. Data collection included: reason for admission, gender, age, clinical signs and symptoms of B12 deficiency, serum B12 concentration, and B12 supplementation. Patients with dementia were identified based on their medication profile and medical history. Vitamin B12 deficiency (pmol/L) was defined as serum B12 concentration148; marginal deficiency: ≥148-220 and adequate220. Comparisons between B12-deficient patients with and without dementia were examined using parametric and non-parametric tests.Serum B12 values were available for 60% (399/666) of the patients, of whom 4% (16/399) were B12-deficient and 14% (57/399) were marginally deficient. Patients with dementia were not more likely to be B12-deficient or marginally deficient [21% (26/121)] compared to those with no dementia [17% (47/278), p=0.27)]. Based on documentation, 34% (25/73) of the B12-deficient and marginally-deficient patients did not receive B12 supplementation, of whom 40% (10/25) had dementia.In this sample of patients, there was no association between B12 deficiency and dementia. However, appropriate B12 screening protocols are necessary for high risk patient to identify deficiency and then receive B12 supplementation as needed.

Triple negative breast cancer (TNBC) is a highly metastatic disease that currently lacks effective prevention and treatment strategies. The insulin-like growth factor 1 receptor (IGF1R) and focal adhesion kinase (FAK) signaling pathways function in numerous developmental processes, and alterations in both are linked with a number of common pathological diseases. Overexpression of IGF1R and FAK are closely associated with metastatic breast tumors. The present study investigated the interrelationship between IGF1R and FAK signaling in regulating the malignant properties of TNBC cells. Using small hairpin RNA (shRNA)-mediated IGF1R silencing methods, we showed that IGF1R is essential for sustaining mesenchymal morphologies of TNBC cells and modulates the expression of EMT-related markers. We further showed that IGF1R overexpression promotes migratory and invasive behaviors of TNBC cell lines. Most importantly, IGF1R-driven migration and invasion is predominantly mediated by FAK activation and can be suppressed using pharmacological inhibitors of FAK. Our findings in TNBC cells demonstrate a novel role of the IGF1R/FAK signaling pathway in regulating critical processes involved in the metastatic cascade. These results may improve the current understanding of the basic molecular mechanisms of TNBC metastasis and provide a strong rationale for co-targeting of IGF1R and FAK as therapy for mesenchymal TNBCs.

A major achievement of reading research has been the development of effective intervention programs for struggling readers. Most intervention studies employ a pre-post design, to examine efficacy, but this precludes the study of growth curves over the course of the intervention program. Determining the time-course of improvement is essential for cost-effective, evidence-based decisions on the optimal intervention dosage. The goal of this study was to analyze reading growth curves during an intensive summer intervention program. A cohort of 31 children (6–12 years) with reading difficulties (N = 21 with dyslexia diagnosis) were enrolled in 160 h of intervention occurring over 8 weeks of summer vacation. We collected behavioral measures over 4 sessions assessing decoding, oral reading fluency, and comprehension. Mixed-effects modeling of longitudinal measurements revealed a linear dose-response relationship between hours of intervention and improvement in reading ability; there was significant linear growth on every measure of reading skill and none of the measures showed non-linear growth trajectories. Decoding skills showed substantial growth [Cohen’s d = 0.85 (WJ Basic Reading Skills)], with fluency and comprehension growing more gradually [d = 0.41 (WJ Reading Fluency)]. These results highlight the opportunity to improve reading skills over an intensive, short-term summer intervention program, and the linear dose-response relationship between duration and gains enables educators to set reading level goals and design a treatment plan to achieve them.

Perfluorocarbon nanodroplets (PFCnDs) are a tool used in ultrasound (US) as a contrast agent and therapeutic delivery vehicle. When loaded with a photoabsorber, PFCnDs can also provide photoacoustic (PA) contrast, as they undergo a laser-triggered phase change from droplet to bubble. Utilizing this phase-changing behavior, we have investigated the ability of laser-activated PFCnDs to open the blood brain barrier (BBB) and deliver an encapsulated photoabsorber across the BBB. This method of BBB opening could enable non-invasive delivery of contrast or therapeutics to the brain tissue under US/PA image guidance, resulting in a safe, efficient, and cost-effective approach to studying neurological diseases.

Introduction Road traffic accidents (RTAs) are the leading cause of trauma related mortality in Ireland. The penalty points system (PPS) was introduced in Ireland in 2002 to incentivise safer driving and reduce injury. Its early effect was studied previously 1 which concluded that there was a slight reduction in RTA related femoral shaft fractures (a sensitive indicator of high energy trauma) and a dramatic reduction in RTA related discharges. We hypothesized that over the following 14 years, the penalty points system might lose its effectiveness. Methods Data was again collected from the same HIPE departments from six Dublin teaching hospitals and also University Hospital Waterford (to represent both an urban and a more rural population cohort respectively) examining RTA related femoral shaft fractures over an identical 6 month period (October–April). RTA related discharge data over an identical 6 month period was again acquired and analysed from Beaumont Hospital, Dublin (identical data source to previous study). These results were compared with the identical 6 month period in 2001/02 & 2002/03 (October–April). Results The total number of RTA related femoral shaft fracture discharges in Dublin decreased from 16 post introduction of PPS in the 2002/03 6-month period to 7 in 2015/16 6-month period. The number remained the same in the Waterford region (n = 5). The total RTA related discharges in Beaumont Hospital, Dublin decreased from 70 post PPS introduction to 57 in the 2015/16 6-month period. This represents an incidence rate of 4.5/1000 discharges (vs 6.9 post introduction) which was a statistically significant reduction (p = 0.014). The mean length of stay for these patients reduced from 13 to 7.7 days. There were consistent reductions in head injury (major & minor), lower limb fracture and facial fracture since the introduction of the PPS. The upper limb, pelvic/acetabular and thoracic injuries remained largely unchanged. Whilst RTA related spinal and abdominal injuries decreased after the introduction of the PPS, this study shows that these injuries have unfortunately increased since the post-PPS study in 2002/03. Conclusions These results further support the effectiveness of the penalty points system and at a time where road death figures are under the spotlight, endorse the efficacious strategies implemented by the road safety authority in Ireland.

It is well established that visual sensitivity to motion is correlated with reading skills. Yet, the causal relationship between motion sensitivity and reading skills has been debated for more than thirty years. One hypothesis posits that dyslexia is caused by deficits in the motion processing pathway. An alternative hypothesis explains the motion processing deficit observed in dyslexia as the consequence of a lack, or poor quality, of reading experience. Here we used an intensive reading intervention program to test the causal relationship between learning to read and motion processing in children. Our data show that, while the reading intervention enhanced reading abilities, learning to read did not affect motion sensitivity. Motion sensitivity remained stable over the course of the intervention. Furthermore, the motion sensitivity deficit did not negatively impact the learning process. Children with poor motion sensitivity showed the same improvement in reading skills as children with typical motion sensitivity. Our findings call into question the view that motion processing deficits are due to poor reading experience. We propose that the correlation between the two measures arises from other common mechanisms, or that motion processing deficits are among a collection of correlated risk factors for reading difficulties.

Resistance to the human epidermal growth factor receptor (HER2)-targeted antibody trastuzumab is a major clinical concern in the treatment of HER2-positive metastatic breast cancer. Increased expression or signaling from the insulin-like growth factor-1 receptor (IGF-1R) has been reported to be associated with trastuzumab resistance. However, the specific molecular and biologic mechanisms through which IGF-1R promotes resistance or disease progression remain poorly defined. In this study, we found that the major biologic effect promoted by IGF-1R was invasion, which was mediated by both Src-focal adhesion kinase (FAK) signaling and Forkhead box protein M1 (FoxM1). Cotargeting IGF-1R and HER2 using either IGF-1R antibodies or IGF-1R short hairpin RNA in combination with trastuzumab resulted in significant but modest growth inhibition. Reduced invasion was the most significant biologic effect achieved by cotargeting IGF-1R and HER2 in trastuzumab-resistant cells. Constitutively active Src blocked the anti-invasive effect of IGF-1R/HER2 cotargeted therapy. Furthermore, knockdown of FoxM1 blocked IGF-1-mediated invasion, and dual targeting of IGF-1R and HER2 reduced expression of FoxM1. Re-expression of FoxM1 restored the invasive potential of IGF-1R knockdown cells treated with trastuzumab. Overall, our results strongly indicate that therapeutic combinations that cotarget IGF-1R and HER2 may reduce the invasive potential of cancer cells that are resistant to trastuzumab through mechanisms that depend in part on Src and FoxM1.