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Newton's Principia is perhaps the second most famous work of mathematics, after Euclid's Elements. Originally published in 1687, it gave the first systematic account of the fundamental concepts of dynamics, as well as three beautiful derivations of Newton's law of gravitation from Kepler's laws of planetary motion. As a book of great insight and ingenuity, it has raised our understanding of the power of mathematics more than any other work. This heavily annotated translation of the third and final edition (1726) of the Principia will enable any reader with a good understanding of elementary mathematics to easily grasp the meaning of the text, either from the translation itself or from the notes, and to appreciate some of its significance. All forward references are given to illuminate the structure and unity of the whole, and to clarify the parts. The mathematical prerequisites for understanding Newton's arguments are given in a brief appendix.
Use of the herbicide atrazine (ATR) is banned in the European Union; yet, it is still widely used in the USA and Australia. ATR is known to alter testosterone and oestrogen production and thus reproductive characteristics in numerous species. In this proof of concept study, we examined the effect of ATR exposure, at a supra-environmental dose (5 mg/kg bw/day), beginning on E9.5 in utero, prior to sexual differentiation of the reproductive tissues, until 26 weeks of age, on the development of the mouse penis. Notably, this is the first study to specifically investigate whether ATR can affect penis characteristics. We show that ATR exposure, beginning in utero, causes a shortening (demasculinisation) of penis structures and increases the incidence of hypospadias in mice. These data indicate the need for further studies of ATR on human reproductive development and fertility, especially considering its continued and widespread use.
Introduction: Oxygen is commonly administered to prehospital patients presenting with acute myocardial infarction (AMI). We conducted a systematic review to determine if oxygen administration, in AMI, impacts patient outcomes. Methods: We conducted a systematic search using MeSH terms and keywords in Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Central, clinicaltrials.gov and ISRCTN for relevant randomized controlled trials and observational studies comparing oxygen administration and no oxygen administration. The outcomes of interest were: mortality (≤30 days, in-hospital, and intermediate 2-11 months), infarct size, and major adverse cardiac events (MACE). Risk of Bias assessments were performed and GRADE methodology was employed to assess quality and overall confidence in the effect estimate. A meta-analysis was performed using RevMan 5 software. Results: Our search yielded 1192 citations of which 48 studies were reviewed as full texts and a total of 8 studies were included in the analysis. All evidence was considered low or very low quality. Five studies reported on mortality finding low quality evidence of no benefit or harm. Low quality evidence demonstrated no benefit or harm from supplemental oxygen administration. Similarly, no benefit or harm was found in MACE or infarct size (very low quality). Normoxia was defined as oxygen saturation measured via pulse oximetry at ≥90% in one recent study and ≥94% in another. Conclusion: We found low and very low quality evidence that the administration of supplemental oxygen to normoxic patients experiencing AMI, provides no clear harm nor benefit for mortality or MACE. The evidence on infarct size was inconsistent and warrants further prospective examination.
Introduction: Opioids are routinely administered for analgesia to prehospital patients experiencing chest discomfort from acute myocardial infarction (AMI). We conducted a systematic review to determine if opioid administration impacts patient outcomes. Methods: We conducted a systematic search using MeSH terms and keywords in Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Central and Clinicaltrials.gov for relevant randomized controlled trials and observational studies comparing opioid administration in AMI patients from 1990 to 2017. The outcomes of interest were: all-cause short-term mortality (≤30 days), major adverse cardiac events (MACE), platelet activity and aggregation, immediate adverse events, infarct size, and analgesia. Included studies were hand searched for additional citations. Risk of Bias assessments were performed and GRADE methodology was employed to assess quality and overall confidence in the effect estimate. Results: Our search yielded 3001 citations of which 19 studies were reviewed as full texts and a total of 9 studies were included in the analysis. The studies predominantly reported on morphine as the opioid. Five studies reported on mortality (≤30 days), seven on MACE, four on platelet activity and aggregation, two on immediate adverse events, two on infarct size and none on analgesic effect. We found low quality evidence suggesting no benefit or harm in terms of mortality or MACE. However, low quality evidence indicates that opioids increase infarct size. Low-quality evidence also shows reduced serum P2Y12 (eg: clopidogrel and ticagrelor) active metabolite levels and increased platelet reactivity in the first several hours post administration following an increase in vomiting. Conclusion: We find low and very low quality evidence that the administration of opioids in STEMI may be adversely related to vomiting and some surrogate outcomes including increased infarct size, reduced serum P2Y12 levels, and increased platelet activity. We found no clear benefit or harm on patient-oriented clinical outcomes including mortality.
Introduction: There is increasing evidence to support the integration of simulation into medical training; however, no national emergency medicine (EM) simulation curriculum currently exists. Using Delphi methodology, we aimed to identify and establish content validity evidence for EM curricular content best suited for simulation-based training to inform national postgraduate EM training. Methods: A national panel of experts in EM simulation-related education iteratively rated potential curricular topics, on a 4-point scale, to determine those best suited for simulation-based training. After each round, responses were analyzed and topics scoring <2/4 were removed. Remaining topics were resent to the panel for further ratings until consensus was achieved, defined as Cronbach α ≥ 0.95. At conclusion of the Delphi process, topics that were rated ≥3.5/4 were considered core curricular topics, while those rated 3.0-3.5 were considered extended curricular topics. Results: Forty-four experts from 13 Canadian centres participated. Two hundred and eighty potential curricular topics, in 29 domains, were generated from a systematic review of the literature, analysis of relevant educational documents and a survey of Delphi panelists. Three rounds of Delphi surveys were completed before consensus was achieved, with response rates ranging from 93-100%. Twenty-eight topics, in 8 domains, reached consensus as core curricular topics. An additional 35 topics, in 14 domains, reached consensus as extended curricular topics. Conclusion: Delphi methodology allowed for achievement of expert consensus and content validation of EM curricular content best suited for simulation-based training. These results provide a foundation for improved integration of simulation into postgraduate EM training and can be used to inform a national simulation curriculum to supplement clinical training and optimize learning.
We sought to address the prior limitations of symptom checker accuracy by analysing the diagnostic and triage feasibility of online symptom checkers using a consecutive series of real-life emergency department (ED) patient encounters, and addressing a complex patient population – those with hepatitis C or HIV. We aimed to study the diagnostic and triage accuracy of these symptom checkers in relation to an emergency room physician-determined diagnosis. An ED retrospective analysis was performed on 8363 consecutive adult patients. Eligible patients included: 90 HIV, 67 hepatitis C, 11 both HIV and hepatitis C. Five online symptom checkers were utilised for diagnosis (Mayo Clinic, WebMD, Symptomate, Symcat, Isabel), three with triage capabilities. Symptom checker output was compared with ED physician-determined diagnosis data in regards to diagnostic accuracy and differential diagnosis listing, along with triage advice. All symptom checkers, whether for combined HIV and hepatitis C, HIV alone or hepatitis C alone had poor diagnostic accuracy in regards to Top1 (<20%), Top3 (<35%), Top10 (<40%), Listed at All (<45%). Significant variations existed for each individual symptom checker, as some appeared more accurate for listing the diagnosis in the top of the differential, vs. others more apt to list the diagnosis at all. In regards to ED triage data, a significantly higher percentage of hepatitis C patients (59.7%; 40/67) were found to have an initial diagnosis with emergent criteria than HIV patients (35.6%; 32/90). Symptom checker diagnostic capabilities are quite inferior to physician diagnostic capabilities. Complex patients such as those with HIV or hepatitis C may carry a more specific differential diagnosis, warranting symptom checkers to have diagnostic algorithms accounting for such complexity. Symptom checkers carry the potential for real-time epidemiologic monitoring of patient symptoms, as symptom entries and subsequent symptom checker diagnosis could allow health officials a means to track illnesses in specific patient populations and geographic regions. In order to do this, accurate and reliable symptom checkers are warranted.
One of the crucial problems in early modern history continues to be the relationship between the movements commonly called the Renaissance and the Reformation, and the part played by the Northern Humanists in both. Detrimental to its solution has been the comparative neglect of the strategic role of Philipp Melanchthon, as well as the school of humanist educators that graduated from the halls of this Praeceptor Germaniae. In him as in none other, not even Erasmus, we have the full convergence of Northern Humanism with the Protestant Reformation. On the other hand, some scholars have mistakenly assumed that the emphasis on the Bible among the German reformers led to its domination of their schools.
Elevated levels of pro-inflammatory cytokines are consistently reported in schizophrenia (SZ) and bipolar-I disorder (BD), as well as among individuals who have been exposed to childhood trauma. However, higher levels of inflammatory markers in these disorders are yet to be investigated with respect to levels of exposure to different types of childhood trauma.
Participants were 68 cases with a diagnosis of schizophrenia/schizoaffective disorder (SZ), 69 cases with a diagnosis of psychotic BD and 72 healthy controls (HC). Serum levels of interleukin 6 (IL-6), tumour necrosis factor-α (TNF-α) and C-reactive protein (CRP) were quantified, and childhood trauma exposure was assessed with the Childhood Trauma Questionnaire.
The SZ group had significantly higher levels of IL-6, TNF-α and CRP when compared with the HC group (all p < 0.05, d = 0.41–0.63), as well as higher levels of TNF-α when compared with the BD group (p = 0.014, d = 0.50); there were no differences between the BD and HC groups for any markers. Exposure to sexual abuse was positively associated (standardised β = 0.326, t = 2.459, p = 0.018) with levels of CRP in the SZ group, but there were no significant associations between any form of trauma exposure and cytokine levels in the HC or BD groups.
These results contribute to the evidence for a chronic state of inflammation in SZ but not BD cases. Differential associations between trauma exposure and levels of pro-inflammatory cytokines across the diagnostic categories suggest that trauma may impact biological (stress and immune) systems differently in these patient groups.
The Vietnam draft lottery exposed millions of men to risk of induction at a time when the Vietnam War was becoming increasingly unpopular. We study the long-term effects of draft risk on political attitudes and behaviors of men who were eligible for the draft in 1969–1971. Our 2014–2016 surveys of men who were eligible for the Vietnam draft lotteries reveal no appreciable effect of draft risk across a wide range of political attitudes. These findings are bolstered by analysis of a vast voter registration database, which shows no differences in voting rates or tendency to register with the Democratic or Republican parties. The pattern of weak long-term effects is in line with studies showing that the long-term economic effects of Vietnam draft risk dissipated over time and offers a counterweight to influential observational studies that report long-term persistence in the effects of early experiences on political attitudes.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
There are no estimates of the heritability of phenotypic udder traits in suckler sheep, which produce meat lambs, and whether these are associated with resilience to mastitis. Mastitis is a common disease which damages the mammary gland and reduces productivity. The aims of this study were to investigate the feasibility of collecting udder phenotypes, their heritability and their association with mastitis in suckler ewes. Udder and teat conformation, teat lesions, intramammary masses (IMM) and litter size were recorded from 10 Texel flocks in Great Britain between 2012 and 2014; 968 records were collected. Pedigree data were obtained from an online pedigree recording system. Univariate quantitative genetic parameters were estimated using animal and sire models. Linear mixed models were used to analyse continuous traits and generalised linear mixed models were used to analyse binary traits. Continuous traits had higher heritabilities than binary with teat placement and teat length heritability (h2) highest at 0.35 (SD 0.04) and 0.42 (SD 0.04), respectively. Udder width, drop and separation heritabilities were lower and varied with udder volume. The heritabilities of IMM and teat lesions (sire model) were 0.18 (SD 0.12) and 0.17 (SD 0.11), respectively. All heritabilities were sufficiently high to be in a selection programme to increase resilience to mastitis in the population of Texel sheep. Further studies are required to investigate genetic relationships between traits and to determine whether udder traits predict IMM, and the potential benefits from including traits in a selection programme to increase resilience to chronic mastitis.
The prevalence of mental disorders among Black, Latino, and Asian adults is lower than among Whites. Factors that explain these differences are largely unknown. We examined whether racial/ethnic differences in exposure to traumatic events (TEs) or vulnerability to trauma-related psychopathology explained the lower rates of psychopathology among racial/ethnic minorities.
We estimated the prevalence of TE exposure and associations with onset of DSM-IV depression, anxiety and substance disorders and with lifetime post-traumatic stress disorder (PTSD) in the Collaborative Psychiatric Epidemiology Surveys, a national sample (N = 13 775) with substantial proportions of Black (35.9%), Latino (18.9%), and Asian Americans (14.9%).
TE exposure varied across racial/ethnic groups. Asians were most likely to experience organized violence – particularly being a refugee – but had the lowest exposure to all other TEs. Blacks had the greatest exposure to participation in organized violence, sexual violence, and other TEs, Latinos had the highest exposure to physical violence, and Whites were most likely to experience accidents/injuries. Racial/ethnic minorities had lower odds ratios of depression, anxiety, and substance disorder onset relative to Whites. Neither variation in TE exposure nor vulnerability to psychopathology following TEs across racial/ethnic groups explained these differences. Vulnerability to PTSD did vary across groups, however, such that Asians were less likely and Blacks more likely to develop PTSD following TEs than Whites.
Lower prevalence of mental disorders among racial/ethnic minorities does not appear to reflect reduced vulnerability to TEs, with the exception of PTSD among Asians. This highlights the importance of investigating other potential mechanisms underlying racial/ethnic differences in psychopathology.
In 2016, imported Zika virus (ZIKV) infections and the presence of a potentially competent mosquito vector (Aedes albopictus) implied that ZIKV transmission in New York City (NYC) was possible. The NYC Department of Health and Mental Hygiene developed contingency plans for a urosurvey to rule out ongoing local transmission as quickly as possible if a locally acquired case of confirmed ZIKV infection was suspected. We identified tools to (1) rapidly estimate the population living in any given 150-m radius (i.e. within the typical flight distance of an Aedes mosquito) and (2) calculate the sample size needed to test and rule out the further local transmission. As we expected near-zero ZIKV prevalence, methods relying on the normal approximation to the binomial distribution were inappropriate. Instead, we assumed a hypergeometric distribution, 10 missed cases at maximum, a urine assay sensitivity of 92.6% and 100% specificity. Three suspected example risk areas were evaluated with estimated population sizes of 479–4,453, corresponding to a minimum of 133–1244 urine samples. This planning exercise improved our capacity for ruling out local transmission of an emerging infection in a dense, urban environment where all residents in a suspected risk area cannot be feasibly sampled.
We assess how likely Americans are to support political candidates
who are Muslim, and the extent to which support for Muslim
candidates is structured by “cultural outgroup
antipathy”—generalized antipathy targeting cultural outgroups. We
employ two survey experiments included in the 2007 and 2010
Cooperative Congressional Election Studies that juxtapose a
hypothetical state legislative candidate's Muslim faith with Arab
ethnicity, African American race, and both Democratic and Republican
party affiliation. Identifying a candidate as Muslim significantly
reduces voter support and that reduction is largest among people
with higher levels of cultural outgroup antipathy. The effect is
consistent regardless of whether the candidate is also identified as
being Arab or African American or is just presented as a Muslim. We
also find that cultural outgroup antipathy diminished electoral
support for same-party Muslim candidates among Democrats but not
Introduction: Our emergency department (ED) sees a low volume of high acuity pediatric cases. A needs assessment revealed that 68% of our Emergency Physicians (EP) manage pediatric patients in less than 25% of their shifts. The same percentage of EPs as well as ED nurses indicated they were uncomfortable managing a critically unwell neonate. Thus, an interprofessional curriculum focused on pediatric emergencies for ED staff was developed. In-situ simulation education was chosen as the most appropriate method to consolidate each didactic block of curriculum, and uncover important system gaps. Methods: Needs assessment conducted, and emerging themes informed IPE curriculum objectives. A committee of experts in simulation, pediatric emergencies and nursing education designed a full-day, RCPSC accredited, interprofessional in-situ simulation program. Results: Progressive segmental strategy maximized learning outcomes. The initial phase (2 hrs) comprised an” early recognition of sepsis” seminar and 4 rotating skills stations (equipment familiarity, sedating the child, IV starts, and mixing IV medication). This deliberate, adaptive, customized practice was enhanced by expert facilitation at each station, directly engaging participants and providing real-time feedback. The second phase allowed interprofessional teams of MDs, RNs and Physician Assistants to apply knowledge gained from the didactic and skills stations to in-situ simulated emergencies. Each group participated in two pediatric emergency scenarios. Scenarios ran 20 minutes, followed by a 40 minute debrief. Each scenario had a trained debriefer and content expert. The day concluded with a final debrief, attended by all participants. Formalized checklists assessed participants knowledge translation during simulation exercises. Participants assessed facilitators and evaluated the simulation day and curriculum via anonymous feedback forms. Debriefing sessions were scribed and knowledge gaps and system errors were recorded. Results were distributed to ED leaders and responsibilities assigned to key stakeholders to ensure accountability and improvement in system errors. Results All participants reported the experience to be relevant and helpful in their learning. All participants requested more frequent simulation days. System gaps identified included: use of metric vs imperial measurements, non-compatible laryngoscope equipment, inadequate identification of team personnel. As a result, the above-mentioned equipment has been replaced, and we are developing resuscitation room ID stickers for all team roles. Conclusion: Simulation as a culmination to a didactic curriculum provides a safe environment to translate acquired knowledge, increasing ED staff comfort and familiarity with rare pediatric cases. Additionally, is an excellent tool to reveal system gaps and allow us to fill these gaps to improve departmental functioning and safety.
Introduction: BACKGOUND In the modern era of terrorism and senseless violence, it is essential that hospital staff have expertise in implementation of a mass casualty incident (MCI) plan. OBJECTIVES 1. To assess current gaps in implementation of an academic urban hospital code orange plan using live simulation and tabletop exercise. 2. To identify and educate front-line staff to champion a hospital-wide MCI plan. INNOVATION Historically, in order to limit resource utilization and impact on patient care, disaster response training of front-line staff involved tabletop exercises only. The tenets of experiential learning suggest that learner engagement through realistic active practice of skills achieves deeper uptake of new knowledge. We enhanced the traditional tabletop approach through novel use of live actor patients presenting to an academic, urban emergency department (ED) during a hospital-wide MCI simulation. Methods: To assess the current code orange plan, an interprofessional, committee comprising expert leaders in trauma, emergency preparedness, emergency medicine and simulation integrated tabletop and live simulation to stage a MCI based on a mock incident at a new subway station. ED staff, the trauma team and champions from medicine, surgery and critical care participated along with support departments such as Patient Flow, Patient Transport, Environmental Services and the Hospital Emergency Operations Centre. Ten live actor patients and eight virtual patients presented to the ED. The exercise occurred in situ in the ED. Other participating departments conducted tabletop exercises and received live actor patients. Results: CURRICULUM Staff decanted the ED and other participating units using their current knowledge of hospital code orange policy. Live and virtual patients were triaged and managed according to severity of injuries. Live actor patients were assessed, intervened and transported to their designated unit. Virtual patients were managed through verbal discussion with the simulation controllers. An ED debrief took place using a plus/delta approach followed by a hospital-wide debrief. Conclusion: CONCLUSION An interprofessional hospital-wide MCI simulation revealed important challenges such as communication, command and control and patient-tracking . The exercise ignited enthusiasm and commitment to longitudinal practice and improvement for identified gaps.
The wandering of a wing-tip vortex in free-stream turbulence was documented by analysis of multi-probe hot-wire measurements in a wind tunnel and flow visualisation and particle image velocimetry measurements in a water tunnel. An error-minimisation approach was applied to the hot-wire measurements to estimate the time history of the location of the vortex axis, whereas flow visualisation from two orthogonal views permitted the reconstruction of relatively long sections of the vortex axis. The amplitude of the wandering motion was found to scale with the turbulence intensity, the core radius and the vortex turnover time; this amplitude was insensitive to changes in the integral length and time scales of the turbulence. The period of the vortex wandering was distributed in the range between 1 and 10 vortex turnover times. The wavelength of wandering was distributed at a relatively long value, which scaled with the vortex turnover time. The velocity of vortex wandering depended on the vortex turnover time, but also contained an additional contribution that was consistent with motion induced by bending waves. The prevalence of the vortex turnover time as the scale for vortex wandering was interpreted as evidence that vortex-induced straining of the free-stream eddies bounds the interaction time between the two, thus limiting the time available for linear and angular momentum transfer.
Nutritional management of pigs to optimise growth demands pig-specific, time-specific and place-specific determination and provision of nutritional requirement. These elements need to be incorporated into response prediction models that operate in a real-time (not retrospective) closed-loop control environment. This implies appropriate means for the on-line measurement of response to change in nutrient provision, and the simultaneous means for manipulation of feeding level and feed quality. The paper describes how response prediction modelling and response measurement may now be achieved. Optimisation may be pursued with mixed objectives, including those of production efficiency and environmental protection.
There is a high and increasing proportion of
single-parent families in Jamaica. This has raised
concerns about the potential impact of single-parent
families on the social, cognitive and behavioural
development of children, including their sexual
relationships. The aim of this study was to
investigate the association between being raised in
a single-parent family and age of sexual debut among
young people in Jamaica. The study was
cross-sectional in design, and based on a
multi-stage sampling procedure. The study was
conducted in July/September 2016. The study sample
comprised 233 respondents (110 males and 123
females) aged from 18 to 35 years (mean 26.37 years;
SD 5.46). Respondents completed a self-administered
questionnaire with questions on socio-demographic
characteristics, family structure, sexual debut and
current sexual behaviour. Ninety-seven (41.7%)
respondents grew up in single-parent families. A
total of 201 (86.3%) had had sex (102 males and 99
females). Their mean age of sexual debut was 15.51
years (SD 3.41). Sixty-five (32.3%) had early sexual
debut (<16 years). Respondents from
single-parent families were more likely to have had
early sexual debut (56.9%; n=37)
compared with those from two-parent families (43.1%,
p=0.004). Only 44.6%
(n=29) of those who experienced
early sexual debut used a condom during their first
sexual encounter compared with 73%
(n=100) of those who had a later
sexual debut (≥16 years;
p=<0.001). A single-father
family structure was a significant predictor of
early sexual debut (AOR 5.5; 95%CI: 1.1–25.8). The
study found a significant association between
single-parent family structure and age of sexual
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.