Y N Do you require any vehicles entering the farm to be disinfected prior to entry and upon exiting? Y N Do you require that visitors avoid livestock areas purchase 300 mg lopid fast delivery medicine dosage chart, pens buy lopid 300mg mastercard medications given for adhd, and barns unless absolutely necessary? Y N Do you restrict close contact or handling of animals by visitors (unless necessary for the health of the animal)? Cleaning and Disinfection Y N Do you clean and disinfect any non-disposable items that come in contact with eye or nasal discharges 300 mg lopid for sale treatment action group, manure lopid 300mg with visa symptoms zenkers diverticulum, urine, saliva, or milk from an infected animal? Y N Do you dispose of bedding and manure from isolation areas so that livestock or wildlife do not have access to it? Y N Do you remove dirt and organic material (bedding, manure) before applying disinfectants? Y N Are boot baths properly maintained (proper concentration used, changed frequently to keep clean)? Conclusion Total number of: Yes responses ________ No responses ________ If you have 1 or more No responses, you have identifed areas for improvement on your farm. Not all questions are equal in their risk of disease transmission, so it is important to work with your veterinarian to develop a management plan addressing the biggest risks frst. This will help minimize the chance of foot-and-mouth disease from entering your farm. Each farm will be unique in their ability to prevent disease transmission because management styles, herd sizes and fnances vary. Overview of Parkinson’s Disease Parkinson’s disease is a progressive and chronic neurodegenerative brain disorder that affects approximately 1 million people in the United States. Parkinson’s disease affects both men and women; however, men are one and a half times more likely than women to have the disease. The condition is generally characterized by primary motor symptoms of resting tremor, bradykinesia, rigidity, and postural instability. Non-motor symptoms experienced by Parkinson’s disease patients may include cognitive impairment, mood disorders, and sleep disturbances. The progression of Parkinson’s disease may differ markedly from patient to patient following diagnosis. There is no cure for Parkinson’s disease; therefore, the goals for treatment are to improve quality of life and manage the signs and symptoms of the disease. Several treatment options for Parkinson’s disease are currently available and involve a wide range of administration routes including tablets, capsules, patches, subcutaneous injections, intramuscular injections and intrajejunal infusions. Carbidopa-levodopa remains the mainstay of treatment for the signs and symptoms of Parkinson’s disease. Over the course of their disease, almost all patients with Parkinson’s disease will take carbidopa-levodopa. Deep brain stimulation is also a potential therapeutic option for patients with advanced Parkinson’s disease. Non-pharmacological management approaches include exercise, yoga, meditation, diet, and lifestyle modification. Discussion focused on two key topics: (1) the effects of Parkinson’s disease that matter most to patients, and (2) patients’ perspectives on treatments for Parkinson’s disease. The discussion questions (Appendix 1) were published in a Federal Register notice that announced the meeting. For each topic, a panel of patients and patient representatives (Appendix 2) shared comments to begin the dialogue. Panel comments were followed by a facilitated discussion inviting comments from other patients and patient representatives in the audience. Participants who joined the meeting via live 3 webcast (referred to in this report as web participants) were also able to contribute comments. In addition, in-person and web participants were periodically invited to respond to polling questions (Appendix 3), which provided a sense of the demographic makeup of participants and of how many participants shared a particular perspective on a given topic. Approximately 45 Parkinson’s disease patients and patient representatives attended the meeting in- person, and approximately 10 patients or patient representatives provided input through the live webcast. According to their responses to the polling questions, in-person and web participants represented an even distribution of gender. A majority of meeting participants identified themselves as having received a Parkinson’s disease diagnosis less than ten years ago. To supplement the input gathered at the meeting, patients and others were encouraged to submit 2 comments on the topic to a public docket, which was open until November 23, 2015. A few patient groups and healthcare providers also submitted surveys and patient group responses to the public docket. More information, including the archived webcast and meeting transcript, is available on the meeting website: http://www. To the extent possible, the terms used in this report to describe specific Parkinson’s disease symptoms, impacts, and treatment experiences reflect the words used by in-person participants, web participants, or docket commenters. The report is not meant to be representative in any way of the views and experiences of any specific group of individuals or entities. There may be symptoms, impacts, treatments, or other aspects of Parkinson’s disease that are not included in this report. The input from the meeting and docket comments underscore the debilitating effect that Parkinson’s disease has on patients’ lives and the challenges patients face in finding therapy to manage the multiple challenges caused by their condition. Several key themes emerged from this meeting: • Parkinson’s disease is a progressive, devastating disease. Participants emphasized the difficulty of living with the unexpected onset and progression of symptoms. Many described living with daily motor symptoms which included bradykinesia, dyskinesia, tremor and dystonia. In addition to motor symptoms, participants also highlighted sleep disturbances, cognitive impairment, fatigue, and constipation. Participants described severe limitations in performing at work, caring for self and family, and maintaining relationships. Participants described the burden of selecting the best available treatments to address their symptoms, the complexity of managing proper timing of medications in addition to pill burden (number and frequency of pills taken throughout the day), and the need for adjustment of their medication regimen because of unpredictable symptoms, changes in daily demands leading to increases in symptoms, as well as disease progression. Participants emphasized that the side effects of treatments were often as debilitating as the underlying disease symptoms. Many participants highlighted the benefits of incorporating non- drug therapies, such as exercise and diet modifications, with prescription regimens for optimal symptom management. For example, Appendix 4 shows how this input may directly support our benefit-risk assessments for products under review. In addition, the report may be useful to drug developers as they explore potential areas of unmet need for Parkinson’s disease patients such as limiting disease progression or increasing symptom control. It could also point to the potential need for development and qualification of new outcome measures in clinical trials. Topic 1: Disease Symptoms and Daily Impacts That Matter Most to Patients The first discussion topic focused on patients’ experiences with their Parkinson’s disease symptoms and the resulting effects on their daily lives. Five panelists (Appendix 2) provided comments to start the dialogue, including two women and three men. The panelists provided a range of experiences with Parkinson’s disease: two panelists spoke of experiencing symptoms for several years prior to diagnosis, two panelists described living with Parkinson’s disease for over twenty-five years, and one panelist shared her late mother’s experiences with Parkinson’s disease progression. Panelists described living with the symptoms of Parkinson’s disease and its impact on daily life with compelling detail. During the large-group facilitated discussion, participants indicated by show of hands that their experiences were reflected in the panelists’ comments. Motor symptoms, impaired balance and coordination, cognitive impairment, and sleep disturbances received the highest number of responses. Responding web participants reported similar symptoms to those participating in person.
We should not allow this risk to be dismissed categorically by those who have a vested interest in continuing current farming practices generic lopid 300 mg with mastercard medicine neurontin. We cannot count on new antibiotics to save us from this crisis—the pipeline is inadequate discount lopid 300 mg mastercard x medications. We must do a much better job of preserving the effectiveness of the antibiotics we have now buy lopid 300mg line treatment for hemorrhoids. Because nearly 80 percent of antimicrobial use in the United States is in livestock cheap lopid 300 mg amex medications prescribed for ptsd, we must do a much better job of reducing antibiotic use in livestock as well as in humans. It is important that we not be bogged down or distracted by quibbles over the minutiae of the molecular mechanisms by which antibiotic resistance spreads from animals to humans or the precise proportion of antibiotic-resistant infections in humans that is caused by antibiotic use in animals. The fundamental point is that antibiotic-resistant microbes can move from livestock fed antibiotics to humans, that patients are harmed as a result of this process, and that, in some countries, national policies eliminating growth promotion and routine prophylactic use have reverted or slowed antibiotic resistance rates. Thus, from a policy perspective, the real question is, what is the “pro” of antimicrobial use in animals that might cause society to agree to take on the corresponding “con”—the risk of harming humans by this use? The pro is the ability of industrial farms to take shortcuts in animal husbandry to increase the potential for profit. Do we, as a society, believe that livestock producers should be afforded the right to profligate antimicrobial use by growing animals in unsanitary and crowded conditions despite the clear associated risk of transmission of antibiotic-resistant bacteria from animals to humans, resulting in harm to humans? If we reduce the amount of antibiotics fed to animals by 50 percent per animal, but we grow twice as many animals, we still will be exposing the bacteria in the food production environment to the same amount of antibiotics, driving antibiotic resistance. As a society, if we want to reduce the selection of antibiotic-resistant bacteria, and thereby reduce the risk of antibiotic-resistant infections, we should be consuming less meat. This real, transformative opportunity has had insufficient attention at the level of national health and commerce policy. Johnson has received consulting payments from Crucell/Jannsen and has received research grants from Actavis, Merck, and Thetraphase. Clinical features and aerobic and anaerobic microbiological characteristics of cellulitis. Factors associated with complications and mortality in adult patients hospitalized for infectious cellulitis. Danmap 2014: Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. Recent research examining links among klebsiella pneumoniae from food, food animals, and human extraintestinal infections. Intermingled klebsiella pneumoniae populations between retail meats and human urinary tract infections. Survey of infections due to staphylococcus species: Frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific Region for the sentry antimicrobial surveillance program, 1997–1999. Ceftiofur resistance in Salmonella enterica serovar heidelberg from chicken meat and humans, Canada. Summary report on antimicrobials sold or distributed for use in food-producing animals. Antibiotic resistance: Implications for global health and novel intervention strategies: Workshop summary. Similarity between human and chicken Escherichia coli isolates in relation to ciprofloxacin resistance status. Population-based epidemiology and microbiology of community-onset bloodstream infections. Changes in intestinal flora of farm personnel after introduction of a tetracycline-supplemented feed on a farm. Use of sulfasuxidine, streptothricin, and streptomycin in nutritional studies with the chick. Reduced and responsible: Use of antibiotics in food- producing animals in the Netherlands. Foodborne urinary tract infections: A new paradigm for antimicrobial-resistant foodborne illness. Antimicrobials in agriculture and the environment: Reducing unnecessary use and waste: The review on antimicrobial resistance. Medical and economic impact of extraintestinal infections due to Escherichia coli: Focus on an increasingly important endemic problem. Rising plague: The global threat from deadly bacteria and our dwindling arsenal to fight them. In Antibiotic resistance: Implications for global health and novel intervention strategies: Workshop summary. The epidemic of antibiotic-resistant infections: A call to action for the medical community from the Infectious Diseases Society of America. Recommended design features of future clinical trials of anti-bacterial agents for community- acquired pneumonia. Antimicrobial agents for complicated skin and skin structure infections: Justification of non-inferiority margins in the absence of placebo-controlled trials. Nosocomial bloodstream infections in pediatric patients in United States hospitals: Epidemiology, clinical features and susceptibilities. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. There is no ideal antimicrobic An antimicrobic or antimicrobial agent is Selective Toxicity - Drugs that specifically target a chemical substance similar to an microbial processes, and not the human host’s. Antibiotics Spectrum of antibiotics and targets • Naturally occurring antimicrobials – Metabolic products of bacteria and fungi – Reduce competition for nutrients and space • Bacteria – Streptomyces, Bacillus, • Molds – Penicillium, Cephalosporium * * 1 The mechanism of action for different 5 General Mechanisms of Action for antimicrobial drug targets in bacterial cells Antibiotics - Inhibition of Cell Wall Synthesis - Disruption of Cell Membrane Function - Inhibition of Protein Synthesis - Inhibition of Nucleic Acid Synthesis - Anti-metabolic activity Antibiotics weaken the cell wall, and cause the cell to lyse. Cell wall synthesis • Bactericidal • Vancomycin – hinders peptidoglycan elongation • Penicillin and cephalosporins – binds and blocks peptidases involved in cross-linking the glycan molecules Fig. Affect cell wall synthesis The mechanism of cell wall inhibition by penicillins and cephalosporins Penicillin – Figure 13. Penicillin V, ampicillin or other analogues may be used for oral administration Cephalosporins - similar to penicillins 2 Penicillin Penicillin continued • Penicillin chrysogenum • Resistance – if bacteria contain • A diverse group (1st, 2nd , 3rd generations) penicillinases - ββββ-lactamase – Natural (penicillin G and V) • Inhibits cell wall synthesis – Semisynthetic (ampicillin, amoxicillin) • Effective against Gram+ bacteria • Structure –Beta-lactam ring – Variable side chain (R group) Effect of β-lactamase on penicillin Penicillins Cephalosporin - beta lactam Cephalosporin continued… • Cephalosporium acremonium (mold) • Resistant to most pencillinases • Widely administered today • Broad-spectrum – inhibits cell wall – Diverse group (natural and semisynthetic- th synthesis 4 generation! Moreover, once they have entered the environ- Accepted 7 February 2017 ment, antibiotics can affect natural microbial communities. The latter play a key role in fundamental ecological Available online 10 February 2017 processes, most importantly the maintenance of soil and water quality. In fact, they are involved in biogeochem- Keywords: icalcyclingandorganiccontaminantdegradationthankstotheirlargereservoirofgeneticdiversityandmetabol- Antibiotic effects ic capability. When antibiotics occur in the environment, they can hamper microbial community structure and Natural microbial communities functioning in different ways and have both direct (short-term) and indirect (long-term) effects on microbial Biodegradation communities. The short-term ones are bactericide and bacteriostatic actions with a consequent disappearance Antibiotic resistance genes of some microbial populations and their ecological functioning. The indirect impact includes the development of antibiotic resistant bacteria and in some cases bacterial strains able to degrade them by metabolic or co-met- abolic processes. Biodegradation makes it possible to completely remove a toxic compound from the environ- ment if it is mineralized. This review describes the current state of knowledge regarding the effects of antibiotics on natural microbial communities in soil and water ecosystems. Introduction mitosanes, anthracenones, enediynes and epothilones) or pesticides (such as oxytetracycline and streptomycin) [7,8]. Pharmaceuticals are essential for the maintenance of public health Antibioticscurrently in use are natural, synthetic and semi-synthetic and life quality. Semi-synthetic taminants in soil andwaterecosystems[1,2] thanks to an increase in the compounds are natural antibiotics chemically altered by inserting an ability to detect them with advanced chemical analyses. Among the var- additive within the drug formulation, which improves its effectiveness ious pharmaceuticals, the presence of antibiotics in soil and water eco- (more stable and less biodegradable). Antimicrobials are compounds categories (Table 1), based on their action mechanism: the inhibition of that can kill or inhibit the growth of microorganisms (bacteria, archaea, cell wall synthesis, alteration of cell membranes, protein synthesis inhi- viruses, protozoa, microalgae and fungi).
However generic lopid 300mg amex symptoms rotator cuff injury, massive experimental infections cause illness or death in rats discount lopid 300mg otc jnc 8 medications, dogs buy lopid 300 mg free shipping medications covered by medi cal, cats purchase lopid 300 mg on line medications kidney failure, and swine; the infected animals exhibit peripheral eosinophilia, fever, anorexia, emaciation, and muscle pain. Source of Infection and Mode of Transmission: Trichinosis in nature is an infection of wild animals. The parasite circulates between predatory carnivores and omnivorous or necrophagous animals. The former become infected by hunting and consuming the latter, and the latter become infected by eating the carcasses of the former. From the epidemiological standpoint, the parasite’s resistance to putrefac- tion is important; live, often infective, larvae have been found in badly decayed flesh for up to four months, which facilitates the infection of carrion eaters. A domestic, peridomestic, or synanthropic cycle derives from this wild cycle when synanthropic animals such as rats, dogs, cats, and swine become infected by eating infected wild animals and carry the infection to the domestic environment. In places where modern technology is applied to swine breeding, such as Japan and Switzerland, the wild cycle can exist without extending to the domestic environment (Gotstein et al. There is some evidence that the infection can also extend from the domestic to the wild environment: Minchella et al. It is assumed that, once in the domestic environment, the parasite circulates among pigs, dogs, cats, and rats. The parasite is transmitted from pig to pig mainly by the ingestion of food scraps containing raw pork. The incidence of trichinosis in swine fed raw waste from kitchens, restaurants, or slaughterhouses is 20 times higher than that in grain-fed swine. Another source of infection for swine may be dead infected animals, including rats, but also dogs, cats, or wild animals, which are sometimes found in garbage dumps. One theory is that the consumption of infected rats explains the swine infections which, in turn, cause outbreaks of the infection in man. While it is true that an association between high rates of infection in rats and swine has sometimes been found, there is also solid research that casts doubt on this association (Campbell, 1983). Infection of swine by chewing the tails of other (infected) swine has also been described. Dogs and cats probably become infected when they eat scraps of infected raw pork provided by their owners or by hunting infected rats or ingesting infected dead domestic, peridomestic, or wild animals. Sled dogs in the Arctic are infected by eat- ing wild animal meat fed to them by man or by consuming carrion they find in their habitat. This explains the extremely high rates (50% or more) found among dogs in that region. In turn, dog and cat carcasses transmit the infection to other carrion eaters, rats, and swine. Rats become infected by eating infected domestic or wild animals and by canni- balism. The role of the rat in the epidemiology of trichinosis, considered central for a long time, has not been objectively proven. In the opinion of most modern inves- tigators, its epidemiological role seems to be secondary. Man is an accidental host in whom the parasite finds a dead end, except in unusual circumstances, such as in eastern Africa, where some tribes abandon the dead or dying to the hyenas. The human infection occurs mainly as a result of consuming raw or undercooked pork or pork by-products, but also as a result of eating wild game. It is estimated that the meat of a single parasitized pig weighing 100 kg can be a potential source of infection for 360 persons. Since pork is frequently added to beef in the manufacture of sausage, the potential risk is even greater. In Argentina and Chile, outbreaks most commonly occur in rural areas, with the source of infec- tion being a pig killed by its owner and thus not subjected to veterinary inspection. The sources of infection are almost always pigs fed waste from kitchens, restaurants, or local slaughterhouses and, in small towns, animals kept at garbage dumps. However, even pigs inspected in slaughterhouses can give rise to infections, albeit probably mild infections, since trichinoscopy cannot detect low-level parasitoses (fewer than 1–3 larvae per gram of muscle). In Alaska, half the cases were due to bear meat and the other half to walrus meat. In man, as in animals, the frequency of the infection and its intensity increase with age, as a result of longer opportunity for infection and reinfection. The prevalence of trichinosis is very low among Muslims, Jews, and Seventh Day Adventists, whose religious beliefs prohibit the consumption of pork. In the Middle East, the disease occurs in Lebanon, where the Christian population is large, but is very rare in the predominantly Muslim countries. In the former Soviet Union, the habit of consum- ing raw salt pork (which contains muscle fibers) explains why this product is one of the main sources of infection. Food preservation technology and the peculiarities of the different variants of Trichinella also influence the occurrence and prevalence of trichinellosis. For example, viable larvae have been found in bear meat frozen at an ambient temperature of –32°C for several weeks, and in walrus meat kept in a home freezer at –12°C for a month. Most outbreaks in Argentina and Chile occur in winter or early spring when home slaughter of pigs is more frequent. Neighbors usually participate in sausage-making and eat the recently made products at community meals. In some parts of the world, such as the Arctic and Subarctic and eastern Africa, the meat of wild animals constitutes the main source of human infection. In Africa, three outbreaks are known to have been caused by consumption of bush pig (Potamochoerus porcus) meat. Although the immediate source of human infection was the meat of wild swine, the main reservoirs seem to be wild canids, especially hyenas. Nevertheless, an epidemic was recorded in Greenland in 1947 that caused 300 cases and 33 deaths. The origin of that epidemic was not discovered, but in a later out- break, the source of infection was found to be walrus meat. Two more outbreaks were subsequently described in Alaska due to the consumption of walrus meat (Margolis et al. The relative rarity of clinical cases at those latitudes is explained by the low intensity of the parasitosis in wild animals. Outside the Arctic region, cases of human trichinosis whose source of infection was bear meat have occurred. In several European countries, infection due to bear or wild boar meat is playing an increasing role in the epidemiology of the disease, and outbreaks of this nature have been described in the former Czechoslovakia and the former Soviet Union (Ruitenberg et al. There were also 58 cases of trichinosis in China due to consumption of bear meat (Wang and Luo, 1981) and 87 in Japan (Yamaguchi, 1991). Diagnosis: The clinical diagnosis of trichinosis is difficult due to its nonspecific symptomatology and its similarity to common infectious diseases such as influenza. Individual or sporadic cases are often confused with other diseases, but the diagno- sis can be supported by the epidemiological circumstances (such as the recent con- sumption of pork or bear meat and the concurrent occurrence of other, similar cases) and with confirmation of peripheral eosinophilia, increased enzymes that indicate muscle damage, and increased erythrosedimentation. This technique is rarely used in man because it is painful and of limited utility. It is justified only for ruling out collagen diseases with which trichinosis may be confused. Some authors still recommend the use of undefined mixtures as antigens (Sandoval et al. In a high percentage of cases, these antibodies persisted up to 11 months after the study. It was also possible to detect IgA antibodies, which were pre- sumed to have been of intestinal origin, in 62% of the patients in the first month of the disease; their detection is important, since patients can be treated with anthelmintics at that stage. The indirect immunofluorescence test was somewhat less sensitive (95%), but became negative faster (van Knapen et al. A prob- lem with immunobiologic reactions is that they take about three weeks to appear and last months or years.
Recall that India discount lopid 300mg line medicine 801, in contrast discount lopid 300mg visa medicine x ed, displayed a suspiciously large number for excess female mortality under the perinatal and congenital headings cheap lopid 300mg otc medications given for adhd, as well as under “Injuries” safe lopid 300 mg medicine bag. As we have seen before, China is different from both sub-Saharan Africa and India. It has a similar number of missing women, but the bulk of them—around 37% and plausibly more, up to 45%—are to be found at birth. Thereafter, the highest numbers occur for the lowest age group (0–4) and then for the three oldest age groups (60 and older). Excess female child mortality is due mainly to Group 1 diseases; particularly those classiﬁed under “respiratory” and “perinatal”. The disquiet raised by these numbers is not unlike that felt when examining the Indian case under the “perinatal” or “congenital” headings. Once again, the excess female deaths occur in China because women die at a rate closer to that of men from these diseases relative to developed countries. Overall, the percentage of missing women due to non-communicable diseases is similar for India and China, though the composition by disease is distinct. In India, there are excess female deaths due to cancer, and in China there are far more women dying from respiratory diseases. Maternal conditions play a role in explaining the number of missing women in both India and sub-Saharan Africa but not in China. Finally, as far as “Injuries” are concerned, the situation seems to lie further away from sub-Saharan Africa and closer to India, where “Injuries” form a large component of excess female deaths. As in India, there are also missing women from “intentional” injuries caused by deliberate acts of violence: the 30–44 and 45–59 categories appear to be particularly hard hit. As in the case of India and sub-Saharan Africa, disease composition seems to have little to do with excess female mortality in China. In the two major age groups with (post-natal) missing females, there appears to be little or no composition effect. In the age category 0–4, the effect is, if anything, reversed: the changing composition of disease is associated with higher excess female mortality. There is a deﬁnite effect in the 60–69 age category, where disease- by-disease comparisons account for a little over two-thirds of the missing women. Otherwise, the epidemiological transition does not appear to account for many missing females. Certainly, if we go by the overall numbers, the transition explains under 8% of all missing women in China. The proﬁle of age-speciﬁc relative death rates supports the contention that males and females died far more equally in 1900 in the United States than they do now. By the same criterion applied to developing countries today, women were at a relative disadvantage then. The upper curve plots the male-to-female relative death rates in the devel- oped regions today; it is exactly the same curve as in Figure 1. As far as relative death rates by age in the United States in 1900 go, the latter then looked much like sub-Saharan Africa and India look today. The data that go into Figure 3 allow us to quickly form estimates of missing women by age in the United States in 1900. We do so in Table 8, which recalls the three developing regions as well for easy comparison. This is because the female population in 1900 in the United States was around 37 million, while the corresponding number for sub-Saharan Africa is around 350 million. As a proportion of the female population, the total for 1900 in the United States is actually larger than in India or China today. What is more, with the exception of the youngest age group (0–4), the pattern of missing women in the United States in 1900 is quite similar to that of India and sub-Saharan Africa today (examine the table with the mental scaling of 10). We rely on the Historical Census Reports from the Vital Statistics department of the United States. There are some differences between the way this data is presented and the counterpart tables for now-developing regions (Tables 5– 7). A scaling of roughly 15 would put the numbers on par with India, and of around 20 with China. Nevertheless, the table unearths a pattern of missing women in the historical data similar to that in developing countries today. A notable exception is that there appears to be signiﬁcantly fewer missing girls (aged 0 to 4) in the historical data. One major reason for this (at least relative to India and China) is that there is very little respiratory female deﬁcit in the historical United States in 1900, while these two deﬁcits are signiﬁcantly large in India and China. These deﬁcits, by the way, point directly to pre- and post-natal gender discrimination in India and China in a way that does not seem to have been present in the historical United States, and possibly not in modern sub-Saharan Africa. Modern developed regions do not have a large enough number of tuberculosis-related deaths at early ages to allow us to form reference death ratios with any degree of conﬁdence. As soon as those reference ratios become reliable (post age 30), we do see a large number of excess female deaths due to tuberculosis. Among non-communicable disease, apoplexy and Bright’s disease were recorded as leading killers. However, apoplexy was used to describe any death that began with a sudden loss of consciousness, especially if death followed soon after. So, for instance, death from cardiac ﬁbrillation, a ruptured aneurysm, and perhaps even some perinatal or respiratory conditions were likely all clumped together. We have included apoplexy under “cardiovascular diseases” in line with the present classiﬁcation system, but be aware that this probably accounts for at least some deaths in other categories. Similarly, Bright’s disease is an older classiﬁcation for different forms of kidney disease. The term is no longer employed, as the relevant complex of kidney diseases would now be classiﬁed by their better understood aetiologies. The same can be said for deaths from “convulsions”, which has been placed in the category of “neuropsychiatric conditions” under the present classiﬁcation. Another difference is reportedly high death rates from non-communicable diseases for ages 0 to 4 in 1900 United States; and there is excess male mortality in this case. The two most signiﬁcant killers in this category are “convulsions” (classiﬁed as a neuropsychiatric condition) and “debility and atrophy” (classiﬁed as congenital anomalies). Neither of these conditions is listed according to these terms in today’s classiﬁcation. Relative to that benchmark, it is possible to trace over 26,500 excess female deaths for women aged less than 30, suggesting that there is a signiﬁcant number of females missing on this score in the historical United States. Our historical dataset for the United States does not provide totals for Groups 1 and 2, and we must construct these ourselves as best we can from the sub-categories. The aggregate excess deaths for the two groups are obtained by adding excess female deaths from sub-categories A–D (we do not aggregate ﬁner subdivisions, as data at those levels are just not comprehensive45). We then obtain estimates for missing women by age by adding over Groups 1, 2, and “Injuries”; recall that these yield estimates that have been purged of compositional effects, and add up (over age) to mwB. Table 9 records these, as also our earlier estimates (mwA) with the compositional effects included. Unlike in developing regions, there appears to be a signiﬁcant disease-composition effect. The shortfall, mwA − mwB, is close to 30% of the total, something that was decidedly not the case for the developing countries studied earlier.