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Modern lifestyle increases the prevalence of obesity and its co-morbidities in the young population. High-salt (HS) diets are associated with hypertension and cardiac remodelling. The present study evaluated the potential effects of cardiometabolic programming induced by HS intake during puberty in lean and obese rats. Additionally, we investigated whether HS could exacerbate the impairment of cardiovascular parameters in adult life due to postnatal early overnutrition (PO). At postnatal day 3 (PN3), twenty-four litters of Wistar rats were divided into two groups: normal litter (NL, nine pups/dam) and small litter (SL, three pups/dam) throughout the lactation period; weaning was at PN21. At PN30, the pups were subdivided into two more groups: NL plus HS (NLHS) and SL plus HS (SLHS). HS intake was from PN30 until PN60. Cardiovascular parameters were evaluated at PN120. SL rats became overweight at adulthood due to persistent hyperphagia; however, HS exposure during puberty reduced the weight gain and food intake of NLHS and SLHS. Both HS and obesity raised the blood pressure, impaired baro- and chemoreflex sensitivity and induced cardiac remodelling but no worsening was observed in the association of these factors, except a little reduction in the angiotensin type-2 receptor in the hearts from SLHS animals. Our results suggest that the response of newborn offspring to PO and juveniles to a HS diet leads to significant changes in cardiovascular parameters in adult rats. This damage may be accompanied by impairment of both angiotensin signalling and antioxidant defence in the heart.
Sitophilus zeamais is a key pest of stored grains. Its control is made, usually, using synthetic insecticides, despite their negative impacts. Botanical insecticides with fumigant/repellent properties may offer an alternative solution. This work describes the effects of Anethum graveolens, Petroselinum crispum, Foeniculum vulgare and Cuminum cyminum essential oils (EOs) and (S)-carvone, cuminaldehyde, estragole and (+)-fenchone towards adults of S. zeamais. Acute toxicity was assessed by fumigation and topical application. Repellence was evaluated by an area preference bioassay and two-choice test, using maize grains. LC50 determined by fumigation ranged from 51.8 to 535.8 mg L−1 air, with (S)-carvone being the most active. LD50 values for topical applications varied from 23 to 128 µg per adult for (S)-carvone > cuminaldehyde > A. graveolens > C. cyminum > P. crispum. All EOs/standard compounds reduced significantly the percentage of insects attracted to maize grains (65–80%) in the two-choice repellence test, whereas in the area preference bioassay RD50 varied from 1.4 to 45.2 µg cm−2, with cuminaldehyde, (S)-carvone and estragole being strongly repellents. Petroselinum crispum EO and cuminaldehyde affected the nutritional parameters relative growth rate, efficiency conversion index of ingested food and antifeeding effect, displaying antinutritional effects toward S. zeamais. In addition, P. crispum and C. cyminum EOs, as well as cuminaldehyde, showed the highest acetylcholinesterase inhibitory activity in vitro (IC50 = 185, 235 and 214.5 µg mL−1, respectively). EOs/standard compounds exhibited acute toxicity, and some treatments showed antinutritional effects towards S. zeamais. Therefore, the tested plant products might be good candidates to be considered to prevent damages caused by this pest.
Both transposition of the great arteries (TGA) previously submitted to a Senning/Mustard procedure and congenitally corrected TGA (cc-TGA) have the systemic circulation supported by the morphological right ventricle, thereby rendering these patients to heart failure events risk. The aim of this study was to evaluate cardiopulmonary exercise test parameters for stratifying the risk of heart failure events in TGA patients.
Retrospective evaluation of adult TGA patients with systemic circulation supported by the morphological right ventricle submitted to cardiopulmonary exercise test in a tertiary centre. Patients were followed up for at least 1 year for the primary endpoint of cardiac death or heart failure hospitalisation. Several cardiopulmonary exercise test parameters were analysed as potential predictors of the combined endpoint and their predictive power were compared (area under the curve).
Cardiopulmonary exercise test was performed in 44 TGA patients (8 cc-TGA), with a mean age of 35.1 ± 8.4 years. The primary endpoint was reached by 10 (22.7%) patients, with a mean follow-up of 36.7 ± 26.8 months. Heart rate at anaerobic threshold had the highest area under the curve value (0.864), followed by peak oxygen consumption (pVO2) (0.838). Heart rate at anaerobic threshold ≤95 bpm and pVO2 ≤20 ml/kg/min had a sensitivity of 87.5 and 80.0% and a specificity of 82.4 and 76.5%, respectively, for the primary outcome.
Heart rate at anaerobic threshold ≤95 bpm had the highest predictive power of all cardiopulmonary exercise test parameters analysed for heart failure events in TGA patients with systemic circulation supported by the morphological right ventricle.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Using validated psychological assessment instruments, this study examined the psychological distress associated with potential language barriers experienced by over 135 000 Puerto Rican residents who either temporarily or permanently migrated to the continental United States with the landfall of Hurricane Maria in 2017.
Participants were Puerto Rican residents (n = 107) who remained in Puerto Rico (control) or left the island for at least 3 months because of Hurricane Maria (migrants). Participants completed an online survey in their preferred language (Spanish or English), which assessed self-reported English language proficiency, Kessler Psychological Distress Scale (K6), Posttraumatic Stress Disorder Checklist for DSM 5, Patient Health Questionnaire 9-item depression scale, and the Generalized Anxiety Disorder 7-item scale. It was hypothesized that migrants with lower self-reported English proficiency would have comparatively higher indices of post-disaster distress than those with a higher proficiency.
Dividing the migrant group by preferred language for questionnaire completion, the Fisher’s exact test showed significant differences in prevalence of severe mental distress, as defined by K6 scores above 13, between the Spanish-preferring migrants (30.4%), English-preferring migrants (0%), and controls (9.6%).
Our results support a possible correlation between decreased language proficiency in post-disaster migrants and a higher risk factor for severe mental distress.
Survival and infectivity of trypanosomatids rely on cell-surface and secreted glycoconjugates, many of which contain a variable number of galactose residues. Incorporation of galactose to proteins and lipids occurs along the secretory pathway from UDP-galactose (UDP-Gal). Before being used in glycosylation reactions, however, this activated sugar donor must first be transported across the endoplasmic reticulum and Golgi membranes by a specific nucleotide sugar transporter (NST). In this study, we identified an UDP-Gal transporter (named TcNST2 and encoded by the TcCLB.504085.60 gene) from Trypanosoma cruzi, the etiological agent of Chagas disease. TcNST2 was identified by heterologous expression of selected putative nucleotide sugar transporters in a mutant Chinese Hamster Ovary cell line. TcNST2 mRNA levels were detected in all T. cruzi life-cycle forms, with an increase in expression in axenic amastigotes. Confocal microscope analysis indicated that the transporter is specifically localized to the Golgi apparatus. A three-dimensional model of TcNST2 suggested an overall structural conservation as compared with members of the metabolite transporter superfamily and also suggested specific features that could be related to its activity. The identification of this transporter is an important step toward a better understanding of glycoconjugate biosynthesis and the role NSTs play in this process in trypanosomatids.
Regeneration from seed affects species assembly in plant communities, and temperature is the most important environmental factor controlling the germination process. Thermal dependence of seed germination is thus associated with species occurrence in an ecosystem. Hence, we aimed to investigate the role of temperature on seed germination of ten tree species from the western Brazilian Amazon. Seeds were collected in the state of Rondônia, Brazil, and set to germinate under constant temperatures ranging from 10 to 40°C in germination chambers. We calculated germination capacity (G%), germination rate (GR50, reciprocal of germination time), and thermal parameters, such as cardinal temperatures and thermal time requirements. Most species had a large range of temperatures showing G% ≥80%, with optimal temperature varying from 20 to 40°C. Base temperature ranged from 6 to 12°C and ceiling temperatures were mainly >40°C. Astronium lecointei and Parkia nitida showed high germination capacity under temperatures of 35–40°C, while germination of Theobroma cacao dropped from 100% to zero under temperatures between 37 and 40°C. The climax species Cedrela fissilis had the slowest germination time (10 days) and highest thermal time requirement, while seeds of Enterolobium schomburgkii (a late-successional species) germinated within the first day of the experiment. Rapid recruitment of Amazon species could be favoured with treefall disturbance, which increases temperatures in the understory, but sharp limits might be found in the supra-optimal range of temperatures. Such patterns might indicate different regeneration strategies in the tropical rainforest, providing important information regarding seed germination among Amazon species.
With brown adipose tissue (BAT) becoming a possible therapeutic target to counteract obesity, the prenatal environment could represent a critical window to modify BAT function and browning of white AT. We investigated if levels of uncoupling protein 1 (UCP1) and UCP1-mediated thermogenesis are altered in offspring exposed to prenatal obesity. Female CD-1 mice were fed a high-fat (HF) or standard-fat (SF) diet for 3 months before breeding. After weaning, all pups were placed on SF. UCP1 mRNA and protein levels were quantified using quantitative real-time PCR and Western blot analysis, respectively, in brown (BAT), subcutaneous (SAT) and visceral (VAT) adipose tissues at 6 months of age. Total and UCP1-dependent mitochondrial respiration were determined by high-resolution respirometry. A Student’s t-test and Mann–Whitney test were used (significance: P<0.05). UCP1 mRNA levels were not different between the HF and SF offspring. UCP1 protein levels, total mitochondrial respiration and UCP1-dependent respiration were significantly higher in BAT from HF males (P=0.02, P=0.04, P=0.005, respectively) and females (P=0.01, P=0.04, P=0.02, respectively). In SAT, the UCP1 protein was significantly lower in HF females (P=0.03), and the UCP1-dependent thermogenesis was significantly lower from HF males (P=0.04). In VAT, UCP1 protein levels and UCP1-dependent respiration were significantly lower only in HF females (P=0.03, P=0.04, respectively). There were no differences in total respiration in SAT and VAT. Prenatal exposure to maternal obesity leads to significant increases in UCP1 levels and function in BAT in offspring with little impact on UCP1 levels and function in SAT and VAT.
The Schiff base N1,N2-di(2-hydroxy)benzylidenebenzene-1,2-di-imine was prepared from salicylaldehyde and 1,2-diaminobenzene by reflux in ethanol for 6 h obtaining an orange crystalline solid. The Schiff base solid was separated by filtration and washed with ethanol and ethylic ether, and finally, it was dried in a vacuum system for 2 h. The X-ray powder diffraction pattern for this new compound showed that the crystalline compound belongs to the monoclinic system and space group P21/c (No. 14) with refined unit-cell parameters a = 5.9672 (7) Å, b = 16.561 (1) Å, c = 16.337 (2) Å, β = 91.41° (1). The volume of the unit cell is V = 1614.1 (2) Å3.
The right ventricular adaptations early after surgery in infants with tetralogy of Fallot are important to understand the changes that occur later on in life; this physiology has not been fully delineated. We sought to assess early postoperative right ventricular remodelling in patients with tetralogy of Fallot by cardiac MRI.
Materials and method
Subjects with tetralogy of Fallot under 1 year of age were recruited following complete surgical repair for tetralogy of Fallot. Protocol-based cardiac MRI to assess anatomy, function, and flows was performed before hospital discharge using the feed and sleep technique, an unsedated imaging technique.
MRI was completed in 16 subjects at a median age of 77 days (interquartile range 114). There was normal ventricular ejection fraction and indexed right ventricular end-diastolic volume (48±13 cc/m2), but elevated right ventricular mass (z score 6.2±2.4). Subjects requiring a transannular patch or right ventricle to pulmonary artery conduit had moderate pulmonary insufficiency (regurgitant fraction 27±16%).
Early right ventricular remodelling after surgical repair for tetralogy of Fallot is characterised by significant pulmonary regurgitation, right ventricular hypertrophy, and lack of dilation. Performing cardiac MRI using the feed and sleep technique is feasible in infants younger than 5 months. These results might open new avenues to study longitudinal right ventricular changes in tetralogy of Fallot and to further explore the utility of unsedated MRI in patients with other types of CHDs.
DTI is an established method to study cerebral white-matter microstructure. Two established measures of DTI are fractional anisotropy (FA) and mean diffusivity (MD) and both differ for bilingual and monolingual speakers. Less is known about differences in two other measures called radial (RD) and axial diffusivity (AD). We report differences in mean RD and AD-values in the right superior longitudinal fasciculus (SLF) and forceps minor between bilingual (Hindi–English) and monolingual (English) speakers as well as differences in mean FA-values in the anterior thalamic radiation, right inferior fronto-occipital and inferior longitudinal fasciculus (ILF) and mean MD-values in forceps minor and bilateral SLF. Noteworthy, a positive correlation between L2 proficiency and mean RD-values in the right SLF was observed. We suggest that changes in the geometry of white matter tracts reflect regular bilingual language experience and contend that neuroplasticity in right SLF results from demands on cognitive control for bilingual speakers.
Investments have been made to alter the food environment of neighbourhoods that have a disproportionate number of unhealthy food venues. Corner store conversions are one strategy to increase access to fruits and vegetables (F&V). Although the literature shows modest success, the effectiveness of these interventions remains equivocal. The present paper reports on the evaluation of Proyecto MercadoFRESCO, a corner store conversion intervention in two Latino communities.
A repeated cross-sectional design was employed. Data were stratified by intervention arm and bivariate tests assessed changes over time. Logistic and multiple regression models with intervention arm, time and the interaction of intervention and time were conducted. Supplementary analyses account for clustering of patrons within stores and staggering of store conversions.
Three stores were converted and five stores served as comparisons in East Los Angeles and Boyle Heights, California, USA.
Store patrons were interviewed before (n550) and after (n407) the intervention.
Relative to patrons of comparison stores, patrons of intervention stores demonstrated more favourable perceptions of corner stores and increased purchasing of F&V during that store visit. Changes were not detected in store patronage, percentage of weekly dollars spent on food for F&V or daily consumption of F&V.
Consistent with some extant food environment literature, findings demonstrate limited effects. Investments should be made in multilevel, comprehensive interventions that target a variety retail food outlets rather than focusing on corner stores exclusively. Complementary policies limiting the availability, affordability and marketing of energy-dense, nutrient-poor foods should also be pursued.
The parent–child attachment relationship plays an important role in the development of the infant's stress regulation system. However, genetic and epigenetic factors such as FK506 binding protein 51 (FKBP5) genotype and DNA methylation have also been associated with hypothalamus–pituitary–adrenal axis functioning. In the current study, we examined how parent–child dyadic regulation works in concert with genetic and epigenetic aspects of stress regulation. We study the associations of attachment, extreme maternal insensitivity, FKBP5 single nucleotide polymorphism 1360780, and FKBP5 methylation, with cortisol reactivity to the Strange Situation Procedure in 298 14-month-old infants. The results indicate that FKBP5 methylation moderates the associations of FKBP5 genotype and resistant attachment with cortisol reactivity. We conclude that the inclusion of epigenetics in the field of developmental psychopathology may lead to a more precise picture of the interplay between genetic makeup and parenting in shaping stress reactivity.
CVD affect a large proportion of the world’s population, with dyslipidaemia as the major risk factor. The regular consumption of both probiotic bacteria and yeast has been associated with improvement in the serum lipid profile. Thus, the present review aims to describe and discuss the potential mechanisms responsible for the hypocholesterolaemic effect of regular consumption of probiotic bacteria and yeast. Regarding the hypocholesterolaemic effect of probiotic bacteria, the potential mechanisms responsible include: deconjugation of bile salts; modulation of lipid metabolism; and decreased absorption of intestinal cholesterol through co-precipitation of intestinal cholesterol with the deconjugated bile salts, incorporation and assimilation of cholesterol in the cell membrane of the probiotics, intestinal conversion of cholesterol in coprostanol, and inhibition of the expression of the intestinal cholesterol transporter Niemann–Pick C1 like 1 (NPC1L1) in the enterocytes. The potential mechanisms responsible for the hypocholesterolaemic effect of probiotic yeasts include: deconjugation of bile salts; co-precipitation of intestinal cholesterol with the deconjugated bile salts; incorporation and assimilation of cholesterol in the cell membrane; and inhibition of hepatic cholesterol synthesis. The regular consumption of probiotic bacteria and yeast, as a non-pharmaceutical approach to help manage cardiovascular risk, holds promise, according to the beneficial hypocholesterolaemic effects described herein. However, the hypocholesterolaemic effects vary according to the strains used, the physiological state of the host, and the type of diet to which the probiotics are added. Further studies are necessary to fill the gaps with regard to the knowledge related to this topic.
Bicuspid aortic valve is the most common CHD. Its association with early valvular dysfunction, endocarditis, thoracic aorta dilatation, and aortic dissection is well established.
The aim of this study was to assess the incidence and predictors of cardiac events in adults with bicuspid aortic valve.
We carried out a retrospective analysis of cardiac outcomes in ambulatory adults with bicuspid aortic valve followed-up in a tertiary hospital centre. Outcomes were defined as follows: interventional – intervention on the aortic valve or thoracic aorta; medical – death, aortic dissection, aortic valve endocarditis, congestive heart failure, arrhythmias, or ischaemic heart disease requiring hospital admission; and a composite end point of both. Kaplan–Meier curves were generated to determine event rates, and predictors of cardiac events were determined by multivariate analysis.
A total of 227 patients were followed-up over 13±9 years; 29% of patients developed severe aortic valve dysfunction and 12.3% reached ascending thoracic aorta dimensions above 45 mm. At least one cardiac outcome occurred in 38.8% of patients, with an incidence rate at 20 years of follow-up of 47±4%; 33% of patients were submitted to an aortic valve or thoracic aorta intervention. Survival 20 years after diagnosis was 94±2%. Independent predictors of the composite end point were baseline moderate–severe aortic valve dysfunction (hazard ratio, 3.19; 95% confidence interval, 1.35–7.54; p<0.01) and aortic valve leaflets calcification (hazard ratio, 4.72; 95% confidence interval, 1.91–11.64; p<0.005).
In this study of bicuspid aortic valve, the long-term survival was excellent but with occurrence of frequent cardiovascular events. Baseline aortic valve calcification and dysfunction were the only independent predictors of events.
Economic losses due to an increase of leg disorders in broilers have become a major concern of the poultry industry. Despite the efforts to reduce skeletal abnormalities in chickens, insufficient progress has been made. Bacterial chondronecrosis with osteomyelitis (BCO) is one of the main disorders that affect bone integrity in broilers. However, the genetic pathways and genes involved in most bone problems, including BCO, remains unclear. In this study, femoral samples from male broilers with 45 days of age affected or not with BCO were used to compare the relative expression with a reverse transcription real time PCR approach of 13 candidate genes: SPP1 (osteopontin), TNFRSF11B (osteoprotegerin), SPARC (osteonectin), CALB1 (calbidin 1), CALM (Calmodulin 2), IBSP (sialoprotein), COL1A2 (collagen, type I, α 2), BMP2 (bone morphogenetic protein 2), BMP3 (bone morphogenetic protein 3), RANKL (κ-B nuclear factor ligand), SMAD1 (SMAD family member 1), LEPR (leptin receptor) and RUNX2 (related transcription factor Runt 2). Differential expression test between affected and non-affected groups was performed using the REST software. The RUNX2 and SPARC genes were downregulated (P<0.05) in the affected group, with reduced expression of fourfold when compared with the non-affected group. This result indicates that the downregulation of RUNX2 and SPARC can contribute to an increased incidence of BCO in broilers.
Subduction initiation is a cornerstone in the edifice of plate tectonics. It marks the turning point of the Earth's Wilson cycles and ultimately the supercycles as well. In this paper, we explore the consequences of subduction zone invasion in the Atlantic Ocean, following recent discoveries at the SW Iberia margin. We discuss a buoyancy argument based on the premise that old oceanic lithosphere is unstable for supporting large basins, implying that it must be removed in subduction zones. As a consequence, we propose a new conceptual model in which both the Pacific and the Atlantic oceans close simultaneously, leading to the termination of the present Earth's supercycle and to the formation of a new supercontinent, which we name Aurica. Our new conceptual model also provides insights into supercontinent formation and destruction (supercycles) proposed for past geological times (e.g. Pangaea, Rodinia, Columbia, Kenorland).
‘DASH for Asthma’ (n 90) was a 6-month randomized controlled trial that demonstrated potential benefits of a DASH (Dietary Approaches to Stop Hypertension) behavioural intervention for improving diet quality and asthma control by comparing intervention to usual care in adults with uncontrolled asthma. The present study examined acceptability and feasibility of the intervention from the perspective of intervention participants and lifestyle coaches.
Grounded in Social Cognitive Theory, the 3-month intensive stage, including three individual and eight group sessions, focused on diet modifications and behavioural self-regulation. The 3-month maintenance stage contained telephone consultations. Participants and lifestyle coaches completed surveys including 5-point Likert scales and open-ended questions. We analysed data using descriptive and inductive content analyses.
Forty-six intervention participants (survey response rate was 65–72 %) and two lifestyle coaches.
Participants and lifestyle coaches were highly satisfied (all mean ratings >4) with individual and group sessions. Participants identified mastery of knowledge and skills (awareness, goal setting, self-monitoring, problem solving), social learning (class members sharing experiences and ideas) and good coaching skills (reflective listening, empathy, motivational counselling) as important contributors to self-efficacy and programme satisfaction. Participants also valued personalized feedback received in individual sessions. Lifestyle coaches viewed participant engagement as a facilitator to effective sessions. Finally, participants and lifestyle coaches identified food tasting as beneficial for observational learning and facilitation of participant engagement. High class attendance and self-monitoring rate also reflected the high engagement among participants.
The DASH behavioural intervention was feasible and highly acceptable to participants with uncontrolled asthma and lifestyle coaches.
The effects of different dietary levels of maize silage (10% v. 36% DM) and group size (7 v. 14 animals) were assessed on growth performance and in vivo digestibility of 28 male fattening buffaloes. In addition, the effects of diet on meat quality and group size on behaviour and immune response were separately evaluated. Animals were weighed and assigned to three groups. The high silage – low size group (HL) was fed a total mixed ration (TMR) containing 36% DM of maize silage and consisted of seven animals (age 12.7±2.6 months; BW 382.2±67.7 kg at the start of the study). The low silage – low size group (LL) was fed a TMR containing 10% DM of maize silage and consisted of seven animals (age 13.0±2.7 months; BW 389.4±72.3 kg). The high silage – high size group (HH) was fed the 36% maize silage DM diet and consisted of 14 animals (age 13.9±3.25 months; BW 416.5±73.9 kg). Total space allowance (3.2 indoor+3.2 outdoor m2/animal) was kept constant in the three groups, as well as the ratio of animals to drinkers (seven animals per water bowl) and the manger space (70 cm per animal). Growth performance, carcass characteristics and digestibility were influenced neither by dietary treatment nor by group size, even if the group fed 36% maize silage diet showed a higher fibre digestibility. No effect of diet was found on meat quality. Group size did not affect the behavioural activities with the exception of drinking (1.04±0.35% v. 2.60±0.35%; P<0.01 for groups HL and HH, respectively) and vigilance (2.58±0.46% v. 1.20±0.46%; P<0.05 for groups HL and HH, respectively). Immune responses were not affected by group size.
While more and more long-period giant planets are discovered by direct imaging, the distribution of planets at these separations (≳5 AU) has remained largely uncertain, especially compared to planets in the inner regions of solar systems probed by RV and transit techniques. The low frequency, the detection challenges, and heterogeneous samples make determining the mass and orbit distributions of directly imaged planets at the end of a survey difficult. By utilizing Monte Carlo methods that incorporate the age, distance, and spectral type of each target, we can use all stars in the survey, not just those with detected planets, to learn about the underlying population. We have produced upper limits and direct measurements of the frequency of these planets with the most recent generation of direct imaging surveys. The Gemini NICI Planet-Finding Campaign observed 220 young, nearby stars at a median H-band contrast of 14.5 magnitudes at 1”, representing the largest, deepest search for exoplanets by the completion of the survey. The Gemini Planet Imager Exoplanet Survey is in the process of surveying 600 stars, pushing these contrasts to a few tenths of an arcsecond from the star. With the advent of large surveys (many hundreds of stars) using advanced planet-imagers we gain the ability to move beyond measuring the frequency of wide-separation giant planets and to simultaneously determine the distribution as a function of planet mass, semi-major axis, and stellar mass, and so directly test models of planet formation and evolution.